Human Cancer Studies Involving Natural Compounds

Compiled by John G. Connor, M.Ac., L.Ac. Edited by Barbara Connor, M.Ac., L.Ac.

Introduction

What we have compiled below are actual human studies showing how natural compounds can be used either alone or in conjunction with chemotherapy and which may prevent cancer, may enhance the quality of life or may increase survival time in cancer patients. As this is a work in progress we will be adding studies to this compilation as we come across new ones.  As of October 2010 we have compiled a list of 71 different studies involving human cancer and natural compounds.  Barbara and I hope you find this information helpful.

Type of Cancer   No. of Studies
1. Advanced Lung Cancer   1
2. Breast Cancer   15
3. Chronic Lymphocytic Leukemia   1
4. Colorectal Cancer   14
5. General Cancer   17
6. Hepatocellular Cancer   2
7. Non-Hodgkin’s Lymphoma   1
8. Non-Small Cell Lung Cancer   3
9. Ovarian Cancer   3
10. Pancreatic Cancer   4
11. Prostate Cancer   9
12. Uterine Cervical Cancer   1










1.  Advanced Lung Cancer

Effects of water-soluble Ganoderma lucidum polysaccharides on the immune functions of patients with advanced lung cancer.
Preclinical studies have established that the polysaccharide fractions of Ganoderma lucidum have potential antitumor activity. Recent clinical studies have demonstrated that G. lucidum polysaccharides enhance host immune functions [e.g., enhanced natural killer (NK) cell activity] in patients with advanced solid tumors, although an objective response was not observed. This open-label study aimed to evaluate the effects of water-soluble G. lucidum polysaccharides (Ganopoly, Encore International Corp., Auckland, New Zealand) on immune functions in patients with advanced lung cancer. Thirty-six patients were enrolled and treated with 5.4 g/day Ganopoly for 12 weeks. In the 30 cancer patients who completed the trial, treatment with Ganopoly did not significantly alter the mean mitogenic reactivity to phytohemagglutinin, mean counts of CD3, CD4, CD8, and CD56, mean plasma concentrations of interleukin (IL)-2, IL-6, and interferon (IFN)-gamma, or NK activity in the patients, but the results were significantly variable. However, some cancer patients demonstrated markedly modulated immune functions. The changes in IL-1 were correlated with those for IL-6, IFN-gamma, CD3, CD8, and NK activity (P < .05), and IL-2 changes were correlated with those for IL-6, CD8, and NK activity. The results suggest that subgroups of cancer patients might be responsive to Ganopoly in combination with chemotherapy/radiotherapy. Further studies are needed to explore the efficacy and safety of Ganopoly used alone or in combination with chemotherapy-/radiotherapy in lung cancer patients. J Med Food. 2005 Summer;8(2):159-68. (Gao Y, et al 2005)


2.  Breast Cancer
  1. The use of herbal preparations to alleviate climacteric disorders and risk of postmenopausal breast cancer in a German case-control study.
  2. (n-3) fatty acids and cancer therapy.
  3. Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research.
  4. Gamma linolenic acid with tamoxifen as primary therapy in breast cancer.
  5. Expression of sulfotransferases and sulfatases in human breast cancer: Impact on resveratrol metabolism.
  6. Tamoxifen, soy, and lifestyle factors in Asian American women with breast cancer.
  7. Association of ginseng use with survival and quality of life among breast cancer patients.
  8. A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.
  9. Specialty supplements and breast cancer risk in the VITamins And Lifestyle (VITAL) Cohort.
  10. Effect of Coenzyme Q(10), Riboflavin and Niacin on Tamoxifen treated postmenopausal breast cancer women with special reference to blood chemistry profiles.
  11. Dietary intake and serum levels of iron in relation to oxidative stress in breast cancer patients.
  12. Dietary soy intake and breast cancer risk.
  13. Chinese medicinal herbs to treat the side-effects of chemotherapy in breast cancer patients.
  14. Plasma homocysteine and cysteine and risk of breast cancer in women.
  15. Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer.

The use of herbal preparations to alleviate climacteric disorders and risk of postmenopausal breast cancer in a German case-control study.

Obi NChang-Claude JBerger JBraendle WSlanger TSchmidt MSteindorf KAhrens WFlesch-Janys D. Cancer Epidemiol Biomarkers Prev. 2009 Aug;18(8):2207-13.Institute for Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Hamburg, [corrected] Germany. Nadia.Obi@uk-sh.de

Abstract

BACKGROUND: The use of herbal preparations (HEP) to alleviate climacteric disorders is expected to increase as women seek alternatives to menopausal hormone therapy to avoid the associated breast cancer risk. Data are sparse on the long-term effects of HEP containing phytoestrogens and black cohosh on breast cancer risk.METHODS: Within a German case-control study, associations between patterns of HEP use and incident breast cancer were investigated in 10,121 postmenopausal women (3,464 cases, 6,657 controls). Information on HEP use was collected in face-to-face interviews supported by a list of brand names. Multivariate logistic and polytomous regression analyses were done.FINDINGS: Ever use of HEP (9.9%) was inversely associated with invasive breast cancer [odds ratio (OR), 0.74; 95% confidence interval (CI), 0.63-0.87] in a dose-dependent manner (OR, 0.96 per year of use; P = 0.03). Classes of HEP did not differ significantly (P(heterogeneity) = 0.81). Risks for invasive ductal (OR, 0.72; 95% CI, 0.60-0.87) and combined lobular/mixed/tubular tumors (OR, 0.76; 95% CI, 0.58-1.01) were similarly reduced by any HEP use but not for in situ carcinomas (1.34; 95% CI, 0.86-2.09). There were no substantial differences in associations of HEP use by estrogen receptor status (ER(+) OR, 0.74; 95% CI, 0.62-0.89; ER- OR, 0.68, 95% CI, 0.50-0.93) and progesterone receptor status of the tumor.INTERPRETATION: Our findings support the hypothesis that HEP use protects from invasive breast cancer in postmenopausal women. Among conceivable modes of action, those independent of estrogen receptor-mediated pathways seem to be involved (i.e., cytotoxicity, apoptosis).

 (n-3) fatty acids and cancer therapy.

Supplementing the diet of tumor-bearing mice or rats with oils containing (n-3) (omega-3) or with purified (n-3) fatty acids has slowed the growth of various types of cancers, including lung, colon, mammary, and prostate. The efficacy of cancer chemotherapy drugs such as doxorubicin, epirubicin, CPT-11, 5-fluorouracil, and tamoxifen, and of radiation therapy has been improved when the diet included (n-3) fatty acids. Some potential mechanisms for the activity of (n-3) fatty acids against cancer include modulation of eicosanoid production and inflammation, angiogenesis, proliferation, susceptibility for apoptosis, and estrogen signaling. In humans, (n-3) fatty acids have also been used to suppress cancer-associated cachexia and to improve the quality of life. In one study, the response to chemotherapy therapy was better in breast cancer patients with higher levels of (n-3) fatty acids in adipose tissue [indicating past consumption of (n-3) fatty acids] than in patients with lower levels of (n-3) fatty acids. Thus, in combination with standard treatments, supplementing the diet with (n-3) fatty acids may be a nontoxic means to improve cancer treatment outcomes and may slow or prevent recurrence of cancer. Used alone, an (n-3) supplement may be a useful alternative therapy for patients who are not candidates for standard toxic cancer therapies. J Nutr. 2004 Dec;134(12 Suppl):3427S-3430S. (Hardman WE. 2004)

Viscum album L. extracts in breast and gynaecological cancers: a systematic review of clinical and preclinical research.
BACKGROUND: Viscum album L. extracts (VAE, European mistletoe) are a widely used medicinal plant extract in gynaecological and breast-cancer treatment.
METHODS: Systematic review to evaluate clinical studies and preclinical research on the therapeutic effectiveness and biological effects of VAE on gynaecological and breast cancer. Search of databases, reference lists and expert consultations. Criteria-based assessment of methodological study quality.
RESULTS: 19 randomized (RCT), 16 non-randomized (non-RCT) controlled studies, and 11 single-arm cohort studies were identified that investigated VAE treatment of breast or gynaecological cancer. They included 2420, 6399 and 1130 patients respectively. 8 RCTs and 8 non-RCTs were embedded in the same large epidemiological cohort study. 9 RCTs and 13 non-RCTs assessed survival; 12 reported a statistically significant benefit, the others either a trend or no difference. 3 RCTs and 6 non-RCTs assessed tumour behaviour (remission or time to relapse); 3 reported statistically significant benefit, the others either a trend, no difference or mixed results. Quality of life (QoL) and tolerability of chemotherapy, radiotherapy or surgery was assessed in 15 RCTs and 9 non-RCTs. 21 reported a statistically significant positive result, the others either a trend, no difference, or mixed results. Methodological quality of the studies differed substantially; some had major limitations, especially RCTs on survival and tumour behaviour had very small sample sizes. Some recent studies, however, especially on QoL were reasonably well conducted. Single-arm cohort studies investigated tumour behaviour, QoL, pharmacokinetics and safety of VAE. Tumour remission was observed after high dosage and local application. VAE application was well tolerated. 34 animal experiments investigated VAE and isolated or recombinant compounds in various breast and gynaecological cancer models in mice and rats. VAE showed increase of survival and tumour remission especially in mice, while application in rats as well as application of VAE compounds had mixed results. In vitro VAE and its compounds have strong cytotoxic effects on cancer cells.
CONCLUSION: VAE shows some positive effects in breast and gynaecological cancer. More research into clinical efficacy is warranted. J Exp Clin Cancer Res. 2009 Jun 11;28:79. (Kienle GS, Glockmann A, Schink M, Kiene H. 2009)

Gamma linolenic acid with tamoxifen as primary therapy in breast cancer.

Kenny FSPinder SEEllis IOGee JMNicholson RIBryce RPRobertson JF. Int J Cancer. 2000 Mar 1;85(5):643-8.Professorial Unit of Surgery, City Hospital, Nottingham, UK.Gamma linolenic acid (GLA) has been proposed as a valuable new cancer therapy having selective anti-tumour properties with negligible systemic toxicity. Proposed mechanisms of action include modulation of steroid hormone receptors. We have investigated the effects of GLA with primary hormone therapy in an endocrine-sensitive cancer. Thirty-eight breast cancer patients (20 elderly Stage I-II, 14 locally advanced, 4 metastatic) took 8 capsules of oral GLA/day (total = 2.8 g) in addition to tamoxifen 20 mg od (T+GLA). Quality and duration of response were compared with matched controls receiving tamoxifen 20 mg od alone (n = 47). Serial tumour biopsies were taken to assess changes in oestrogen receptor (ER) and bcl-2 expression during treatment. GLA was well tolerated with no major side effects. T+GLA cases achieved a significantly faster clinical response (objective response vs. static disease) than tamoxifen controls, evident by 6 weeks on treatment (p = 0.010). There was significant reduction in ER expression in both treatment arms with T+GLA objective responders sustaining greater ER fall than tamoxifen counterparts (6-week biopsy p = 0.026; 6-month biopsy p = 0.019). We propose GLA as a useful adjunct to primary tamoxifen in endocrine-sensitive breast cancer. The effects of GLA on ER function and the apparent enhancement of tamoxifen-induced ER down-regulation by GLA require further investigation.

Expression of sulfotransferases and sulfatases in human breast cancer: Impact on resveratrol metabolism.
Resveratrol is a naturally occurring anticancer compound present in grapes and wine that undergoes pronounced metabolism in human intestine and liver. In order to determine whether resveratrol is also bio-transformed in human breast carcinoma, metabolism experiments were conducted in breast tumor and adjacent non-tumorous specimens from 13 patients. Resveratrol was metabolized in cytosolic tissue fractions to resveratrol-3-O-sulfate: the formation rates were up to 33.5-fold higher in cancer samples than in peritumoral tissue. Further quantitative real-time RT-PCR analysis revealed similar expression of sulfotransferases SULT1A2, 1A3, and 1E1 in the paired control and tumor tissues. Sulfotransferase SULT1A1 expression was below the detection limit in all samples. Interestingly, mRNA expression of steroid sulfatase STS, but not of arylsulfatases ARS-A and ARS-B, was significantly higher (p<0.0017) in non-malignant specimens than in tumor tissue samples, which might explain the higher resveratrol-3-O-sulfate concentrations in breast cancer specimens. Cellular localization of SULT1A3 and STS was also assessed by indirect immunofluorescence on paraffin-embedded sections from control and malignant breast tissue clearly showing a correlation of qRT-PCR data with protein expression of these two enzymes. Our data elucidate the metabolism of resveratrol in malignant and non-malignant breast tissue, which must be considered in humans after oral uptake of dietary resveratrol as a chemopreventive agent. Cancer Lett. 2009 Sep 9. [Epub ahead of print] (Miksits M, et al 2009)

Tamoxifen, soy, and lifestyle factors in Asian American women with breast cancer.

PURPOSE: Soy foods have been a staple in Asia for centuries but the consumption of this food in the West is recent. Intake of soy among women at high risk for or with breast cancer has become a public health concern because genistein, a major component of soy, has weak estrogenic effects on breast epithelium, and has been found to negate the benefit of tamoxifen in some animal and in vitro studies. PATIENTS AND METHODS: We conducted a cross-sectional study in Asian Americans with breast cancer who were tamoxifen users (n = 380) to investigate the association between soy intake and circulating levels of tamoxifen and its metabolites (N-desmethyl tamoxifen [N-DMT], 4-hydroxytamoxifen [4-OHT], and 4-hydroxy-N-desmethyl-tamoxifen [endoxifen]). RESULTS: Serum levels of tamoxifen or its metabolites were unrelated to self-reported intake of soy or serum levels of isoflavones. Blood levels of tamoxifen were 81% higher in postmenopausal women age 65 or older compared with premenopausal women age 45 or younger (P = .005); similar patterns of results were observed for the tamoxifen metabolites. Levels of N-DMT were 27% (P = .03) lower among women in the highest tertile of body mass index (BMI, > 24.4 kg/m2) compared with those in the lowest category (BMI 21.5). Women who used hypertensive medications had higher levels of tamoxifen (P = .02) and N-DMT (P = .04) compared with nonusers. CONCLUSION: We found no evidence that soy intake adversely affected levels of tamoxifen or its metabolites. However, age, menopausal status, BMI, and use of hypertensive medications significantly influenced circulating levels of tamoxifen and its metabolites in this population. J Clin Oncol. 2007 Jul 20;25(21):3024-30. Epub 2007 May 29. (Wu AH, et al 2007)

Association of ginseng use with survival and quality of life among breast cancer patients.The authors evaluated the associations of ginseng use as a complementary therapy with survival and quality of life (QOL) in a cohort of 1,455 breast cancer patients who were recruited to the Shanghai Breast Cancer Study between August 1996 and March 1998 in Shanghai, China. Patients were followed through December 2002. Information on ginseng use before cancer diagnosis was collected at baseline recruitment and was linked to survival. Survivors’ ginseng use after cancer diagnosis was obtained at the follow-up survey and was correlated to QOL at the same time. The Kaplan-Meier method and Cox regression models were applied to evaluate the association of ginseng use with overall and disease-free survival. The relation of ginseng use and QOL was evaluated by using multiple linear regression models. Approximately 27% of study participants were regular ginseng users before cancer diagnosis. Compared with patients who never used ginseng, regular users had a significantly reduced risk of death; adjusted hazard ratios associated with ginseng use were 0.71 (95% confidence interval: 0.52, 0.98) for total mortality and 0.70 (95% confidence interval: 0.53, 0.93) for disease-specific mortality/recurrence. Ginseng use after cancer diagnosis, particularly current use, was positively associated with QOL scores, with the strongest effect in the psychological and social well-being domains. Additionally, QOL improved as cumulative ginseng use increased. Am J Epidemiol. 2006 Apr 1;163(7):645-53. Epub 2006 Feb 16. (Cui Yet al 2006)

A retrospective case-control study of the use of hormone-related supplements and association with breast cancer.

Rebbeck TRTroxel ABNorman SBunin GRDeMichele ABaumgarten MBerlin MSchinnar RStrom BL. Int J Cancer. 2007 Apr 1;120(7):1523-8.Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6021, USA. trebbeck@cceb.med.upenn.edu

Abstract

Hormone-related supplements (HRS), many of which contain phytoestrogens, are widely used to manage menopausal symptoms, yet their relationship with breast cancer risk has generally not been evaluated. We evaluated whether use of HRS was associated with breast cancer risk, using a population-based case-control study in 3 counties of the Philadelphia metropolitan area consisting of949 breast cancer cases and 1,524 controls. Use of HRS varied significantly by race, with African American women being more likely than European American women to use any herbal preparation (19.2% vs. 14.7%, p=0.003) as well as specific preparations including black cohosh (5.4% vs. 2.0%, p=0.003), ginseng (12.5% vs. 7.9%, p<0.001) and red clover (4.7% vs. 0.6%, p<0.001). Use of black cohosh had a significant breast cancer protective effect (adjusted odds ratio 0.39, 95% CI: 0.22-0.70). This association was similar among women who reported use of either black cohosh or Remifemin (an herbal preparation derived from black cohosh; adjusted odds ratio 0.47, 95% CI: 0.27-0.82). The literature reports that black cohosh may be effective in treating menopausal symptoms, and has antiestrogenic, antiproliferative and antioxidant properties. Additional confirmatory studies are required to determine whether black cohosh could be used to prevent breast cancer.

Specialty supplements and breast cancer risk in the VITamins And Lifestyle (VITAL) Cohort.

Brasky TMLampe JWPotter JDPatterson REWhite E. Cancer Epidemiol Biomarkers Prev. 2010 Jul;19(7):1696-708.Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, M4-B402, Seattle, WA 98109-1024, USA. tbrasky@fhcrc.org

Abstract

BACKGROUND: Use of nonvitamin, nonmineral “specialty” supplements has increased substantially over recent decades. Several supplements may have anti-inflammatory or anticancer properties. Additionally, supplements taken for symptoms of menopause have been associated with reduced risk of breast cancer in two case-control studies. However, there have been no prospective studies of the association between the long-term use of these supplements and breast cancer risk.METHODS: Participants were female members of the VITamins And Lifestyle (VITAL) Cohort. Postmenopausal women, ages 50 to 76 years, who were residents of western Washington State, completed a 24-page baseline questionnaire in 2000 to 2002 (n = 35,016). Participants were queried on their recency (current versus past), frequency (days/week), and duration (years) of specialty supplement use. Incident invasive breast cancers (n = 880) from 2000 to 2007 were obtained from the Surveillance, Epidemiology, and End Results registry. Multivariable-adjusted hazards ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox proportional hazards models.RESULTS: Current use of fish oil was associated with reduced risk of breast cancer (HR, 0.68; 95% CI, 0.50-0.92). Ten-year average use was suggestive of reduced risk (P trend = 0.09). These results held for ductal but not lobular cancers. The remaining specialty supplements were not associated with breast cancer risk: Specifically, use of supplements sometimes taken for menopausal symptoms (black cohosh, dong quai, soy, or St. John’s wort) was not associated with risk.CONCLUSIONS: Fish oil may be inversely associated with breast cancer risk.

Effect of Coenzyme Q(10), Riboflavin and Niacin on Tamoxifen treatedpostmenopausal breast cancer women with special reference to bloodchemistry profiles.
Background Tamoxifen (TAM) a non-steroidal antiestrogen, is widelyused in adjuvant therapy for all stages of breast carcinomas and inchemoprevention of high-risk group. TAM also has estrogenic activityon liver and endometrium causing severe oxidative stress withvarious biochemical derangements. Coenzyme Q(10), Riboflavin and Niacin (CoRN) are well-known potent antioxidants and protective agents against many diseases including cancer. In this context, this study was undertaken to find if co-administration of TAM along with CoRN could alleviate the sole TAM-induced biochemical derangements in postmenopausal women with breast cancer. Method The vitamin supplementation with TAM was given for a period of 90 days. Blood samples were collected at the base line, 45th and 90th day during the course of treatment. Various blood chemistry profiles were assessed in 78 untreated, sole TAM treated and combinatorial treated group along with 46 age- and sex-matched controls. Results A statistically significant alteration in various blood chemistry parameters, such as serum total bilirubin (S. BIL), serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), gamma glutamyl transpeptidase (gamma-GT), uric acid (UA), lipoprotein lipase (LPL), lecithin: cholesterol acyl transferases (LCAT), potassium, calcium and Na(+), K(+)-ATPase in sole TAM-treated group, was favorably reverted back to near normal levels on combinatorial therapy with CoRN. Conclusion TAM on coadministration with CoRN has a favorable impact on various blood chemistry profiles. However, large scale randomized studies over a longer time span are required to ascertain the safety and efficacy of co-administrating antioxidants with conventional chemotherapy. Breast Cancer Res Treat. 2008 Apr 22. [Epub ahead of print] (Yuvaraj S, et al 2008)

Dietary intake and serum levels of iron in relation to oxidative stress in breast cancer patients.

Bae YJYeon JYSung CJKim HSSung MK. J Clin Biochem Nutr. 2009 Nov;45(3):355-60. Epub 2009 Oct 28.Department of Food and Nutrition, Sookmyung Women’s University, Seoul 140-742, Republic of Korea.

Abstract

Iron may induce oxidative stress via production of reactive oxygen species, facilitating mammary carcinogenesis. This study investigated the role of iron in relation to oxidative stress as a potential risk factor in the development of breast cancer (BC). BC patients (n = 121) and healthy age-matched controls (n = 149) were entered into the study. Iron and antioxidant vitamins intakes were estimated using a quantitative food frequency questionnaire. Thirty one subjects from each group provided blood samples for measurement of serum iron, plasma malondialdehyde (MDA) and ferric reducing ability of plasma (FRAP). Total and non-heme iron intake of BC patients were lower than those of the controls. However, the serum iron level was significantly higher in BC patients. Plasma MDA levels were also significantly higher in BC patients whereas no significant difference in FRAP values were observed between the two groups. Log-transformed serum iron concentration showed no significant correlation with MDA or FRAP. These results suggest that serum iron overload may be a breast cancer risk factor possibly due to increased oxidative stress.

Dietary soy intake and breast cancer risk.

Enderlin CAColeman EAStewart CBHakkak R. Oncol Nurs Forum. 2009 Sep;36(5):531-9. (See attached for complete study.)Department of Nursing Education, College of Nursing, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA. caenderlin@uams.edu

Abstract

PURPOSE/OBJECTIVES: To conduct a metasynthesis of the literature on human studies of the relationship between dietary soy intake and breast cancer risk.DATA SOURCES: Publications in English reporting human studies were searched with the terms soy and breast cancer, using Ovid, PubMed, and EBSCO databases. Only human studies investigating the relationship of soy intake to breast cancer development in women published from January 1997 through June 2008 were included in the review.DATA SYNTHESIS: A total of 364 publications were located; 18 of the studies met the inclusion criteria and 18 additional studies were located through other publications identified in the search. Because four articles reported on the same two studies, a total of 34 studies were included in the review.CONCLUSIONS: The naturally occurring dietary intake of soy food or its components appears safe for women without breast cancer; however, the safety of high supplements of soy or its components is less certain.IMPLICATIONS FOR NURSING: Nurses should become more knowledgeable about soy foods and supplements and include soy intake in dietary assessments. Nurses caring for women at high risk for or with a history of breast cancer should confer with dietitians on current practice recommendations. Women with health issues should avoid initiating high intake of soy dietary supplements until the possible effects are better understood.

Chinese medicinal herbs to treat the side-effects of chemotherapy in breast cancer patients.

Zhang MLiu XLi JHe LTripathy D. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD004921.

Abstract

BACKGROUND: Short term side-effects of chemotherapy include fatigue, nausea, vomiting, mucositis and myelosuppression or neutropenia. These occur during the course of treatment and generally resolve within months of completion of chemotherapy. A variety of Chinese medicinal herbs have been used for managing these side effects.OBJECTIVES: To assess the effectiveness and safety of Chinese medicinal herbs in alleviating chemotherapy-induced short term side effects in breast cancer patients.SEARCH STRATEGY: We searched The Cochrane Breast Cancer Specialised Register (15/02/2007), The Cochrane Central Register of Controlled Trials (CENTRAL); (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to December 2006); EMBASE (1990 to December 2006); and Chinese Biomedical Literature (2006, Issue 4). A number of journals were hand searched.SELECTION CRITERIA: Randomised controlled trials comparing chemotherapy with or without Chinese herbs in women with breast cancer.DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data, which were analysed using RevMan 4.2. For dichotomous data, we estimated the relative risk. For continuous data, we calculated the weighted mean difference.MAIN RESULTS: We identified seven randomised controlled trials involving 542 breast cancer patients undergoing or having recently undergone chemotherapy. All studies were conducted and published in China. We did not pool the results because few studies were identified and no more than two used the same intervention. All were of low quality and used CMH plus chemotherapy compared with chemotherapy alone.CMH combined with chemotherapy showed no statistically significant difference for the outcomes of phlebitis and alopecia. Only one study showed an improvement in nausea and vomiting, and in fatigue. Three indicated an improvement in white blood cells in the group receiving CMH. Two showed an increase in percentage changes in T-lymphocyte subsets CD4 and CD8. One study showed a statistically significant difference for CMH in percentage changes in T-lymphocyte subsets CD3, CD4 and CD8. Two herbal compounds may have improved quality of life. One study reported that CMH may have some effect on reducing toxicity in liver and kidney, but differences were not statistically significant.AUTHORS’ CONCLUSIONS: This review provides limited evidence about the effectiveness and safety of Chinese medicinal herbs in alleviating chemotherapy induced short term side effects. Chinese medicinal herbs, when used together with chemotherapy, may offer some benefit to breast cancer patients in terms of bone marrow improvement and quality of life, but the evidence is too limited to make any confident conclusions. Well designed clinical trials are required before any conclusions can be drawn about the effectiveness and safety of CHM in the management of breast cancer patients.

Plasma homocysteine and cysteine and risk of breast cancer in women.

Lin JLee IMSong YCook NRSelhub JManson JEBuring JEZhang SM. Cancer Res. 2010 Mar 15;70(6):2397-405. Epub 2010 Mar 2.Division of Preventive Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA. jhlin@rics.bwh.harvard.edu

Abstract

Homocysteine and cysteine are associated with oxidative damage and metabolic disorders, which may lead to carcinogenesis. Observational studies assessing the association between circulating homocysteine or cysteine and breast cancer are very limited, and findings have been inconsistent. We prospectively evaluated plasma levels of homocysteine and cysteine in relation to breast cancer risk among 812 incident cases of invasive breast cancer and 812 individually matched control subjects from 28,345 women in the Women’s Health Study; these women were >or=45 years old, provided blood samples, and had no history of cancer and cardiovascular disease at baseline. Logistic regression controlling for matching factors and risk factors for breast cancer was used to estimate relative risks (RR) and 95% confidence intervals (95% CI). All statistical tests were two sided. Homocysteine levels were not associated with overall risk for breast cancer. However, we observed a positive association between cysteine levels and breast cancer risk; the multivariate RR for the highest quintile group relative to the lowest quintile was 1.65 (95% CI, 1.04-2.61; P for trend = 0.04). In addition, women with higher levels of homocysteine and cysteine were at a greater risk for developing breast cancer when their folate levels were low (P for interaction = 0.04 and 0.002, respectively). Although our study offers little support for an association between circulating homocysteine and overall breast cancer risk, higher homocysteine levels may be associated with an increased risk for breast cancer among women with low folate status. The increased risk of breast cancer associated with high cysteine levels warrants further investigation.

Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer.

Sato RHelzlsouer KJAlberg AJHoffman SCNorkus EPComstock GW. Cancer Epidemiol Biomarkers Prev. 2002 May;11(5):451-7.Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland 21205, USA.

Abstract

Previous prospective studies have raised the possibility that the antioxidantproperties of carotenoids and vitamin E (alpha-tocopherol) and the role of vitamin A (retinol) in cellular differentiation may be associated with a reduced risk of subsequent breast cancer. To investigate the association between serum and plasma concentrations of retinol, retinyl palmitate, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, lycopene, total-carotenoids, alpha-tocopherol, and gamma-tocopherol with subsequent development of breast cancer, a nested case control study was conducted among female residents of Washington County, Maryland, who had donated blood for a serum bank in 1974 or 1989. Cases (n = 295) and controls (n = 295) were matched on age, race, menopausal status, and date of blood donation, and the analyses were stratified by cohort participation. Median concentrations of beta-carotene, lycopene, and total carotene were significantly lower in cases compared with controls in the 1974 cohort (13.1, 12.5, and 7.9% difference; P = 0.01, 0.04, and 0.04, respectively) and for lutein in the 1989 cohort (6.7% difference; P = 0.02). The risk of developing breast cancer in the highest fifth was approximately half of that of women in the lowest fifth for beta-carotene [odds ratio (OR) = 0.41; 95% confidence interval (CI) 0.22-0.79; P trend = 0.007], lycopene (OR = 0.55; 95% CI 0.29-1.06; P trend = 0.04), and total carotene (OR = 0.55; 95% CI 0.29-1.03; P trend = 0.02) in the 1974 cohort. There was generally a protective association for other micronutrients in both cohorts, although none reached statistical significance. The results suggest that carotenoids may protect against the development of breast cancer.


3.  Chronic Lymphocytic Leukemia

Phase I trial of daily oral Polyphenon E in patients with asymptomatic Rai stage 0 to II chronic lymphocytic leukemia.

Shanafelt TDCall TGZent CSLaPlant BBowen DARoos MSecreto CRGhosh AKKabat BFLee MJYang CSJelinek DFErlichman CKay NE. J Clin Oncol. 2009 Aug 10;27(23):3808-14. Epub 2009 May 26. Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. shanafelt.tait@mayo.edu

Abstract

PURPOSE: To define the optimal dose of Polyphenon E for chronic daily administration and tolerability in patients with chronic lymphocytic leukemia (CLL).PATIENTS AND METHODS: Previously untreated patients with asymptomatic Rai stage 0 to II CLL were eligible for participation. Polyphenon E with a standardized dose of epigallocatechin-3-gallate (EGCG) was administered using the standard phase I design with three to six patients per dose level (range, 400 to 2,000 mg by mouth twice a day). Trough plasma EGCG levels were measured 1 month after initiation of therapy. Response was classified using the National Cancer Institute (NCI) Working Group (WG) Criteria.RESULTS: Thirty-three eligible patients were accrued to dose levels 1 to 8. The maximum-tolerated dose was not reached. The most common adverse effects included transaminitis (33%, all grade 1), abdominal pain (30% grade 1, 0% grade 2, and 3% grade 3), and nausea (39% grade 1 and 9% grade 2). One patient experienced an NCI WG partial remission. Other signs of clinical activity were also observed, with 11 patients (33%) having a sustained > or = 20% reduction in absolute lymphocyte count (ALC) and 11 (92%) of 12 patients with palpable adenopathy experiencing at least a 50% reduction in the sum of the products of all nodal areas during treatment. Trough plasma EGCG levels after 1 month of treatment ranged from 2.9 to 3,974 ng/mL (median, 40.4 ng/mL).CONCLUSION: Daily oral EGCG in the Polyphenon E preparation was well tolerated by CLL patients in this phase I trial. Declines in ALC and/or lymphadenopathy were observed in the majority of patients. A phase II trial to evaluate efficacy using 2,000 mg twice a day began in November 2007.

4.  Colorectal Cancer
  1. Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients.
  2. Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients.
  3. Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene.
  4. Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity.
  5. A Large Prospective Study of Meat Consumption and Colorectal Cancer Risk: An Investigation of Potential Mechanisms Underlying this Association
  6. N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data.
  7. Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial.
  8. High dietary intake of magnesium may decrease risk of colorectal cancer in Japanese men.
  9. Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies.
  10. Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study.
  11. Dietary fatty acids and colorectal cancer: a case-control study.
  12. Serum vitamin D levels and survival of patients with colorectal cancer: post-hoc analysis of a prospective cohort study.
  13. Chinese medical herbs for chemotherapy side effects in colorectal cancer patients.
  14. Clinical observation on treatment of colonic cancer with combined treatment of chemotherapy and Chinese herbal medicine.

Clinical pharmacology of resveratrol and its metabolites in colorectal cancer patients.

Patel KRBrown VAJones DJBritton RGHemingway DMiller ASWest KPBooth TDPerloff MCrowell JABrenner DESteward WPGescher AJBrown K. Cancer Res. 2010 Oct 1;70(19):7392-9. Epub 2010 Sep 14.Cancer Biomarkers and Prevention Group, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, United Kingdom. kp23@le.ac.uk

Abstract

Resveratrol is a phytochemical with chemopreventive activity in preclinical rodent models of colorectal carcinogenesis. Antiproliferation is one of the many chemopreventive modes of action it has been shown to engage in. Concentrations of resveratrol, which can be achieved in human tissues after p.o. administration, have not yet been defined. The purpose of this study was to measure concentrations of resveratrol and its metabolites in the colorectal tissue of humans who ingested resveratrol. Twenty patients with histologically confirmed colorectal cancer consumed eight daily doses of resveratrol at 0.5 or 1.0 g before surgical resection. Resveratrol was found to be well tolerated. Normal and malignant biopsy tissue samples were obtained before dosing. Parent compound plus its metabolites resveratrol-3-O-glucuronide, resveratrol-4′-O-glucuronide, resveratrol-3-O-sulfate, resveratrol-4′-O-sulfate, resveratrol sulfate glucuronide, and resveratrol disulfate were identified by high-performance liquid chromatography (HPLC) with UV or mass spectrometric detection in colorectal resection tissue. Quantitation was achieved by HPLC/UV. Cell proliferation, as reflected by Ki-67 staining, was compared in preintervention and postintervention tissue samples. Resveratrol and resveratrol-3-O-glucuronide were recovered from tissues at maximal mean concentrations of 674 and 86.0 nmol/g, respectively. Levels of resveratrol and its metabolites were consistently higher in tissues originating in the right side of the colon compared with the left. Consumption of resveratrol reduced tumor cell proliferation by 5% (P = 0.05). The results suggest that daily p.o. doses of resveratrol at 0.5 or 1.0 g produce levels in the human gastrointestinal tract of an order of magnitude sufficient to elicit anticarcinogenic effects. Resveratrol merits further clinical evaluation as a potential colorectal cancer chemopreventive agent.

Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients.

Wang WSLin JKLin TCChen WSJiang JKWang HSChiou TJLiu JHYen CCChen PM. Oncologist. 2007 Mar;12(3):312-9.National Yang-Ming University School of Medicine, Taipei, Taiwan, Republic of China.

Abstract

Oxaliplatin is effective in the treatment of metastatic colorectal cancer (MCRC) patients; however, severe neurotoxicity develops frequently. To assess the efficacy of oral glutamine for preventing neuropathy induced by oxaliplatin, a pilot study was performed. A total of 86 patients with MCRC treated at Taipei Veterans General Hospital were enrolled. Oxaliplatin (85 mg/m(2), days 1 and 15) plus weekly bolus 5-fluorouracil (5-FU; 500 mg/m(2)) and folinic acid (FA; 20 mg/m(2)) on days 1, 8, and 15 were given every 28 days as first-line treatment. Patients were randomized to receive (glutamine group; n = 42) or not receive (control group; n = 44) glutamine (15 g twice a day for seven consecutive days every 2 weeks starting on the day of oxaliplatin infusion). Efficacy of chemotherapy, neurological toxicity, and electrophysiological alterations were assessed. A lower percentage of grade 1-2 peripheral neuropathy was observed in the glutamine group (16.7% versus 38.6%) after two cycles of treatment, and a significantly lower incidence of grade 3-4 neuropathy was noted in the glutamine group after four cycles (4.8% versus 18.2%) and six cycles (11.9% versus 31.8%). By adding glutamine, interference with activities of daily living was lower (16.7% versus 40.9%), and need for oxaliplatin dose reduction was lower (7.1% versus 27.3%). There were no significant between-group differences in response to chemotherapy (52.4% versus 47.8%), electrophysiological abnormalities, grade 3-4 non-neurological toxicities (26.2% versus 22.8%), or survival. These data indi-cate that oral glutamine significantly reduces the incidence and severity of peripheral neuropathy of MCRC patients receiving oxaliplatin without affecting response to chemotherapy and survival.


Colorectal cancer protective effects and the dietary micronutrients folate, methionine, vitamins B6, B12, C, E, selenium, and lycopene.

Kune GWatson L. Nutr Cancer. 2006;56(1):11-21.Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia. gkune@unimelb.edu.au

Abstract

The data reported here were obtained from the case-control arm of a large, comprehensive, population-based investigation of colorectal cancer incidence, etiology, and survival, the Melbourne Colorectal Cancer Study, conducted in Melbourne, Australia. This part of the case-control study was designed to identify dietary factors associated with colorectal cancer risk in 715 incident cases compared with 727 age/sex frequency-matched randomly chosen community controls, in which a quantitative assessment of all foods eaten was made. New data are presented on the potential of two groups of micronutrients as protective agents, namely, those involved in DNA methylation, synthesis, and repair (folate, methionine, and vitamins B6 and B12) and those with antioxidant properties (selenium, vitamins E and C, and lycopene). The adjusted odds ratios showed that for folate there was significant protection for rectal cancer in second and third quintiles of consumption but not for colon cancer, and this was similar for methionine consumption. Vitamin B6 consumption was significantly protective for both colon and rectal cancer at the higher quintiles, and this was similar for vitamin B12. Dietary selenium was significantly protective at middle quintiles of consumption at both cancer sites. Dietary vitamins E and C were statistically significantly protective for both colon and rectal cancer at all levels of consumption, and for both vitamins there was a dose-response effect of increasing protection, particularly so for colon cancer. Lycopene was not associated with colorectal cancer risk. A combined model included vitamins E, C, and B12 and selenium as micronutrients protective for colorectal cancer and folate, which, however, showed an increased risk at the highest level of consumption. These data support the proposition that a diet containing the dietary micronutrients involved in DNA methylation (folate, methionine, and vitamins B6 and B12) and some of those with antioxidant properties (selenium and vitamins E and C) may have a role to play in lowering colorectal cancer risk and also that such protection can be achieved by dietary means alone.


Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity.

Milla PAiroldi MWeber GDrescher AJaehde UCattel L. Anticancer Drugs. 2009 Jun;20(5):396-402.Departments of Drug Science and Technology, Turin University, Turin, Italy.

Abstract

Oxaliplatin is a promising drug for cancer therapy and the oxaliplatin/5-fluorouracil/leucovorin (FOLFOX) regimen has become the standard adjuvant treatment for colorectal cancer. However, the oxaliplatin-induced neurotoxicity still represents a clinical problem leading to a discontinuation of the therapy. Many strategies have been proposed in order to manage the neurotoxicity, but their effect on antitumoral efficacy is still unclear. In this study, we investigated the effect of reduced glutathione administration on neurotoxicity, oxaliplatin pharmacokinetics, and platinum-DNA (Pt-DNA) adduct formation in patients affected by colorectal cancer treated with FOLFOX4 adjuvant regimen. Twenty-seven patients were randomized to receive GSH 1500 mg/m or saline solution before oxaliplatin infusion. Evaluation of neurotoxicity, pharmacokinetics of plasmatic total and ultrafiltered Pt, and determination of Pt-DNA adduct formation on white blood cells was performed during the 5th, 9th, and 12th cycles. At the end of all cycles of therapy, the patients in the GSH arm showed a statistically significant reduction of neurotoxicity (P=0.0037) compared with the placebo arm. There were no significant differences in the main pharmacokinetic parameters between the two arms except a lower area under the plasma concentration-time curve and a smaller apparent steady-state volume of distribution (Vss) when GSH was coadministered. This difference can be explained by the natural function of GSH in the detoxification of oxaliplatin and by its ability to remove the Pt bound to plasma proteins. The determination of Pt-DNA adduct formation shows no statistically significant differences between the two arms. In conclusion, this study indicates that coadministration of GSH is an effective strategy to reduce the oxaliplatin-induced neurotoxicity without impairing neither the pharmacokinetics of oxaliplatin, nor the Pt-DNA adduct formation.


A Large Prospective Study of Meat Consumption and Colorectal Cancer Risk: An Investigation of Potential Mechanisms Underlying this Association

Cancer Research 70, 2406, March 15, 2010. Published Online First March 9, 2010;
doi: 10.1158/0008-5472.CAN-09-3929
© 2010 American Association for Cancer Research
Amanda J. Cross1, Leah M. Ferrucci1, Adam Risch4, Barry I. Graubard2, Mary H. Ward3, Yikyung Park1, Albert R. Hollenbeck5, Arthur Schatzkin1 and Rashmi Sinha1Authors’ Affiliations: 1 Nutritional Epidemiology Branch, 2 Biostatistics Branch, and 3 Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Rockville, Maryland; 4 Information Management Services, Inc., Silver Spring, Maryland; and 5 AARP, Washington, District of ColumbiaCorresponding Author: Amanda J. Cross, 6120 Executive Boulevard, Rockville, MD 20852. Phone: 301-496-4378; Fax: 301-496-6829; E-mail: crossa@mail.nih.gov .Although the relation between red and processed meat intake and colorectal cancer has been reported in several epidemiologic studies, very few investigated the potential mechanisms. This study examined multiple potential mechanisms in a large U.S. prospective cohort with a detailed questionnaire on meat type and meat cooking methods linked to databases for estimating intake of mutagens formed in meats cooked at high temperatures (heterocyclic amines, polycyclic aromatic hydrocarbons), heme iron, nitrate, and nitrite. During 7 years of follow-up, 2,719 colorectal cancer cases were ascertained from a cohort of 300,948 men and women. The hazard ratios (HR) and 95% confidence intervals (95% CI) comparing the fifth to the first quintile for both red (HR, 1.24; 95% CI, 1.09–1.42; Ptrend < 0.001) and processed meat (HR, 1.16; 95% CI, 1.01–1.32; Ptrend = 0.017) intakes indicated an elevated risk for colorectal cancer. In general, the elevated risks were higher for rectal cancer than for colon cancer, with the exception of MeIQx and DiMeIQx, which were only associated with colon cancer. In conclusion, we found a positive association for red and processed meat intake and colorectal cancer; heme iron, nitrate/nitrite, and heterocyclic amines from meat may explain these associations. Cancer Res; 70(6); 2406–14


N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data.

Lin PCLee MYWang WSYen CCChao TCHsiao LTYang MHChen PMLin KPChiou TJ. Support Care Cancer. 2006 May;14(5):484-7. Epub 2006 Feb 1.Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taiwan, Republic of China.

Abstract

Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon cancer may improve disease-free survival, grade 3-4 sensory neuropathy also increases. To determine whether oral N-acetylcysteine is neuroprotective against oxaliplatin-induced neuropathy, we did a pilot study. Fourteen stage III colon cancer patients with 4 or more regional lymph nodes metastasis (N2 disease) receiving adjuvant biweekly oxaliplatin (85 mg/m(2)) plus weekly fluorouracil boluses and low-dose leucovorin were randomized to oral N-acetylcysteine (1,200 mg) (arm A) or placebo (arm B). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) Criteria. After four cycles of chemotherapy, seven of nine patients in arm B and two of five in arm A experienced grade 1 sensory neuropathy. After eight cycles, five experienced sensory neuropathy (grade 2-4 toxicity) in arm B; none in arm A (p<0.05). After 12 cycles, grade 2-4 sensory neuropathy was observed in eight patients in arm B, one in arm A (p<0.05). There were no significant electrophysiological changes in arm A after 4, 8, or 12 cycles of chemotherapy. We concluded that oral N-acetylcysteine reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.


Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial.

Cascinu SCatalano VCordella LLabianca RGiordani PBaldelli AMBeretta GDUbiali ECatalano G. J Clin Oncol. 2002 Aug 15;20(16):3478-83.Department of Medical Oncology, Azienda Ospedaliera-Universitaria di Parma, via Gramsci 14, 43100 Parma, Italy. cascinu@yahoo.com

Abstract

PURPOSE: We performed a randomized, double-blind, placebo-controlled trial to assess the efficacy of glutathione (GSH) in the prevention of oxaliplatin-induced neurotoxicity.PATIENTS AND METHODS: Fifty-two patients treated with a bimonthly oxaliplatin-based regimen were randomized to receive GSH (1,500 mg/m(2) over a 15-minute infusion period before oxaliplatin) or normal saline solution. Clinical neurologic evaluation and electrophysiologic investigations were performed at baseline and after four (oxaliplatin dose, 400 mg/m(2)), eight (oxaliplatin dose, 800 mg/m(2)), and 12 (oxaliplatin dose, 1,200 mg/m(2)) cycles of treatment.RESULTS: At the fourth cycle, seven patients showed clinically evident neuropathy in the GSH arm, whereas 11 patients in the placebo arm did. After the eighth cycle, nine of 21 assessable patients in the GSH arm suffered from neurotoxicity compared with 15 of 19 in the placebo arm. With regard to grade 2 to 4 National Cancer Institute common toxicity criteria, 11 patients experienced neuropathy in the placebo arm compared with only two patients in the GSH arm (P =.003). After 12 cycles, grade 2 to 4 neurotoxicity was observed in three patients in the GSH arm and in eight patients in the placebo arm (P =.004). The neurophysiologic investigations (sural sensory nerve conduction) showed a statistically significant reduction of the values in the placebo arm but not in the GSH arm. The response rate was 26.9% in the GSH arm and 23.1% in the placebo arm, showing no reduction in activity of oxaliplatin.CONCLUSION: This study provides evidence that GSH is a promising drug for the prevention of oxaliplatin-induced neuropathy, and that it does not reduce the clinical activity of oxaliplatin.


High dietary intake of magnesium may decrease risk of colorectal cancer in Japanese men.

Ma ESasazuki SInoue MIwasaki MSawada NTakachi RTsugane SJapan Public Health Center-based Prospective Study Group. J Nutr. 2010 Apr;140(4):779-85. Epub 2010 Feb 17.Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.

Abstract

Magnesium maintains genomic stability and is an essential cofactor for DNA synthesis and repair. Magnesium intake has been reported to be inversely associated with colorectal cancer (CRC) risk in Western populations. This study examined the association between dietary intake of magnesium and CRC risk in Japanese men and women aged 45-74 y. Data from 40,830 men and 46,287 women, at the 5-y follow-up of the Japan Public Health Center-based Prospective Study, who responded to a 138-item FFQ were used in this analysis. A total of 689 and 440 CRC events were observed during the mean follow-up of 7.9 and 8.3 y for men and women, respectively. When adjusted for potential confounders, the hazard ratio and 95% CI in the highest quintile of magnesium intake compared with the lowest quintile in men were 0.65 (95% CI, 0.40-1.03) for CRC (P-trend = 0.04), 0.48 (95% CI, 0.26-0.89) for colon cancer (P-trend = 0.01), and 0.97 (95% CI, 0.47-2.02) for rectal cancer (P-trend = 0.93).


Vitamin B6 and risk of colorectal cancer: a meta-analysis of prospective studies.
Larsson SCOrsini NWolk A. JAMA. 2010 Mar 17;303(11):1077-83.Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institutet, PO Box 210, SE-171 77 Stockholm, Sweden. susanna.larsson@ki.se

Abstract

CONTEXT: Mounting evidence indicates that vitamin B(6), a coenzyme involved in nearly 100 enzymatic reactions, may reduce the risk of colorectal cancer.OBJECTIVE: To conduct a systematic review with meta-analysis of prospective studies assessing the association of vitamin B(6) intake or blood levels of pyridoxal 5′-phosphate (PLP; the active form of vitamin B(6)) with risk of colorectal cancer.DATA SOURCES: Relevant studies were identified by a search of MEDLINE and EMBASE databases to February 2010, with no restrictions. We also reviewed reference lists from retrieved articles.STUDY SELECTION: We included prospective studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the association between vitamin B(6) intake or blood PLP levels and the risk of colorectal, colon, or rectal cancer.DATA EXTRACTION: Two authors independently extracted data and assessed study quality. Study-specific RRs were pooled using a random-effects model.DATA SYNTHESIS: Nine studies on vitamin B(6) intake and 4 studies on blood PLP levels were included in the meta-analysis. The pooled RRs of colorectal cancer for the highest vs lowest category of vitamin B(6) intake and blood PLP levels were 0.90 (95% CI, 0.75-1.07) and 0.52 (95% CI, 0.38-0.71), respectively. There was heterogeneity among studies of vitamin B(6) intake (P = .01) but not among studies of blood PLP levels (P = .95). Omitting 1 study that contributed substantially to the heterogeneity among studies of vitamin B(6) intake yielded a pooled RR of 0.80 (95% CI, 0.69-0.92). The risk of colorectal cancer decreased by 49% for every 100-pmol/mL increase (approximately 2 SDs) in blood PLP levels (RR, 0.51; 95% CI, 0.38-0.69).CONCLUSION: Vitamin B(6) intake and blood PLP levels were inversely associated with the risk of colorectal cancer in this meta-analysis.


Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study.

Shimizu MFukutomi YNinomiya MNagura KKato TAraki HSuganuma MFujiki HMoriwaki H. Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3020-5.Department of Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan.

Abstract

BACKGROUND: Experimental studies indicate the chemopreventive properties of green tea extract (GTE) on colorectal cancer. Epidemiologically, green tea consumption of > 10 cups daily reduced colorectal cancer risk in Japanese. Because colorectal adenomas are the precursors to most sporadic colorectal cancers, we conducted a randomized trial to determine the preventive effect of GTE supplements on metachronous colorectal adenomas by raising green tea consumption in the target population from an average of 6 cups (1.5 g GTE) daily to > or = 10 cups equivalent (2.5 g GTE) by supplemental GTE tablets.METHODS: We recruited 136 patients, removed their colorectal adenomas by endoscopic polypectomy, and 1 year later confirmed the clean colon (i.e., no polyp) at the second colonoscopy. The patients were then randomized into two groups while maintaining their lifestyle on green tea drinking: 71 patients supplemented with 1.5 g GTE per day for 12 months and 65 control patients without supplementation. Follow-up colonoscopy was conducted 12 months later in 125 patients (65 in the control group and 60 in the GTE group).RESULTS: The incidence of metachronous adenomas at the end-point colonoscopy was 31% (20 of 65) in the control group and 15% (9 of 60) in the GTE group (relative risk, 0.49; 95% confidence interval, 0.24-0.99; P < 0.05). The size of relapsed adenomas was also smaller in the GTE group than in the control group (P < 0.001). No serious adverse events occurred in the GTE group.CONCLUSION: GTE is an effective supplement for the chemoprevention of metachronous colorectal adenomas.


Dietary fatty acids and colorectal cancer: a case-control study.

Theodoratou EMcNeill GCetnarskyj RFarrington SMTenesa ABarnetson RPorteous MDunlop MCampbell H. Am J Epidemiol. 2007 Jul 15;166(2):181-95. Epub 2007 May 9.Public Health Sciences, University of Edinburgh, Edinburgh, United Kingdom.

Abstract

Fatty acid effects on colorectal cancer risk were examined in a national prospective case-control study in Scotland (1999-2006), including 1,455 incident cases and 1,455 matched controls. Three conditional logistic regression models adjusted for energy (residual method) and for other risk factors were applied in the whole sample and were stratified by sex, cancer site, age, and tumor staging. Total and trans-monounsaturated fatty acids and palmitic, stearic, and oleic acids were dose-dependently associated with colorectal cancer risk, but these effects did not persist after further energy adjustment. Significant dose-dependent reductions in risk were associated with increased consumption of omega-3 polyunsaturated fatty acids (highest vs. lowest quartile of intake: odds ratio = 0.63, 95% confidence interval: 0.50, 0.80; p < 0.0005 for trend) and of eicosapentaenoic (odds ratio = 0.59, 95% confidence interval: 0.47, 0.75; p < 0.0005 for trend) and docosahexaenoic (odds ratio = 0.63, 95% confidence interval: 0.50, 0.80; p < 0.0005 for trend) acids. These associations persisted after including energy with the nutrient-energy-adjusted term or total fatty acid intake (energy adjusted). The observed different effects of different types of fatty acids underline the importance of type of fat in the etiology and prevention of colorectal cancer.


Serum vitamin D levels and survival of patients with colorectal cancer: post-hoc analysis of a prospective cohort study.

Mezawa HSugiura TWatanabe MNorizoe CTakahashi DShimojima ATamez STsutsumi YYanaga KUrashima M. BMC Cancer. 2010 Jul 2;10:347. Division of Molecular Epidemiology, Jikei University School of Medicine, Nishi-shimbashi, Minato-ku, Tokyo, Japan.

Abstract

BACKGROUND: Recently, serum 25-hydroxyvitamin D (25OHD) levels were shown to be associated with the survival of patients with colorectal cancer. However, 25OHD levels were measured a median of 6 years before diagnosis or were predicted levels. In this study, we directly measured serum 25OHD levels at surgery and examined the association with survival among patients with colorectal cancer.METHODS: We started a prospective cohort study to find prognostic factors in patients with colorectal cancer from 2003 to 2008 and stored serum samples and clinical data. As part of a post-hoc analysis, serum 25OHD levels were measured by radioimmunoassay. Association between overall survival and serum 25OHD levels were computed using the Cox proportional hazard model adjusted for month of serum sampling as well as age at diagnosis, gender, cancer stage, residual tumor after surgery, time period of surgery, location of tumor, adjuvant chemotherapy and number of lymph nodes with metastasis at surgery. Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were determined.RESULTS: Serum 25OHD levels were measured in 257 patients. Only 3% had sufficient levels (30 ng/ml and greater). Based on month of blood sampling, an annual oscillation of 25OHD levels was seen, with levels being lower in spring and higher in late summer. Higher 25OHD levels were associated with better overall survival under multi-variate analysis (HR, 0.91: 95% CI, 0.84 to 0.99, P = 0.027).CONCLUSIONS: These results suggest that higher 25OHD levels at surgery may be associated with a better survival rate of patients with colorectal cancer.


Chinese medical herbs for chemotherapy side effects in colorectal cancer patients.

Taixiang WMunro AJGuanjian L. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD004540. Links

Clinical Epidemiology, West China Hospital of Sichuan University, No. 17, Ren Min Nan Lu 3 Duan, Chengdu, Sichuan, China, 610041. txwutx@public.cd.sc.cnBACKGROUND: Side effects, including nausea and vomiting, sore mouth , diarrhoea, hepatotoxicity, myelosuppression, and immunosuppression , are commonly encountered in patients with colorectal cancer who are treated with chemotherapy. A variety of Chinese herbal medicines have been used for managing these adverse effects. OBJECTIVES: To assess the effect of herbal medicines plus chemotherapy, compared with chemotherapy alone, on the side effects of chemotherapy on the quality of life, and on adverse events in patients with colorectal cancer. SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE, CBM, and handsearched the relevant Chinese journals. SELECTION CRITERIA: Randomised trials comparing either chemotherapy only or chemotherapy plus anti-emetics (tropisetron, sulpiride etc) with chemotherapy plus Chinese herbs. DATA COLLECTION AND ANALYSIS: Trial quality was assessed independently by two reviewers. Data were extracted by one reviewer and checked by the second reviewer. Since the four included studies differed significantly in design, we could only perform limited meta-analyses. We have therefore presented the majority of the data in narrative form. MAIN RESULTS: We included four relevant trials. All of them were of low quality. All of studies used a decoction containing Huangqi compounds as the intervention with chemotherapy. The intervention groups of three studies were compared to a chemotherapy alone control group, the fourth study compared the decoction of Huangqi compounds with two other Chinese herbal interventions. None of the studies reported on primary outcome using Common Toxicity Criteria (CTC). There was a significant reduction in the proportion of patients who experienced nausea & vomiting when decoctions of Huangqi compounds were given in addition to chemotherapy. There was also a decrease in the rate of leucopenia. Clinical observation on treatment of colonic cancer with combined treatment of chemotherapy and Chinese herbal medicine.

Zhou LYShan ZZYou JL. Chin J Integr Med. 2009 Apr;15(2):107-11. Epub 2009 Apr 29. Links

Department of Oncology, Wuxi Municipal Hospital of Traditional Chinese Medicine, Jiangsu Province, 214001, China. zhou-liuyong@163.comOBJECTIVE: To observe the clinical effect of combined chemotherapy and Chinese herbal medicine in treating colonic cancer. METHODS: One hundred and sixty-three patients were assigned, according to their will, to two groups, 105 in the traditional Chinese medicine treated group (Group A) and 58 in the combined treatment group (Group B). The Chinese herbal drug Zhao’s Weitiao No. 3 ( 3, ZW3) was given to both groups, twice a day, 40 mL each time, 30 days as one cycle, and over 6 cycles applied in total. For patients in Group B, the chemotherapy of OLF protocol (L-OHP+LV+5-FU) was given for 4-6 cycles. The effects of treatment on the main symptoms, tumor mass, patients’ quality of life (QOL) and body weight, changes of carcino-embryonic antigen (CEA), as well as the integral effect and survival rate were observed and compared. RESULTS: The total effective rate in Group A and Group B was 89.52% and 86.21% respectively, on the main clinical symptoms; 86.67% and 93.10% on tumor mass, 82.86% and 77.59% on QOL, 85.71% and 75.86% on body weight and 76.19% and 79.31% on CEA. The integral efficacy of total beneficial rate was 73.33% and 68.97%; and the 3-year survival rate 49.52% and 46.65% in Group A and Group B. These data showed that the effect in Group A was better than in Group B in terms of clinical symptom improvement, QOL, body weight and integral beneficence increase and survival rate, though it was inferior in reducing the tumor mass and CEA level. CONCLUSION: Chinese drug ZW3 for the treatment of colonic cancer could improve the main clinical symptoms, improve the QOL, increase body weight and prolong the survival time of patients, showing a favorable integral effect.

5.  General Cancers
  1. A systematic review of the effectiveness of Chinese herbal medication in symptom management and improvement of quality of life in adult cancer patients.
  2. Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review.
  3. A pilot study on the effect of acetyl-L-carnitine in paclitaxel- and cisplatin-induced peripheral neuropathy.
  4. Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine.
  5. Acetyl-L-carnitine prevents and reduces paclitaxel-induced painful peripheral neuropathy.
  6. Cancer and Traditional Chinese Medicine – Treating the Side Effects of Chemo-therapy and Radiation with Traditional Chinese Herbs
  7. Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial.
  8. Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation.
  9. Ingestion of selenium and other antioxidants during prostate cancer radiotherapy: A good thing?
  10. A randomized controlled trial evaluating the efficacy and safety of vitamin E supplementation for protection against cisplatin-induced peripheral neuropathy: final results.
  11. Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials.
  12. Protein and ginger for the treatment of chemotherapy-induced delayed nausea.
  13. Effect of citronellol and the Chinese medical herb complex on cellular immunity of cancer patients receiving chemotherapy/radiotherapy.
  14. Antioxidant Supplementation Reduces Incidence Of Cancer in Men
  15. Oral glutamine for the prevention of chemotherapy-induced peripheral neuropathy.
  16. Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1.
  17. Mistletoe therapy in oncology.
A systematic review of the effectiveness of Chinese herbal medication in symptom management and improvement of quality of life in adult cancer patients.
The aim of this systematic review was to assess the effectiveness of Chinese medicinal herbs used concurrently with cancer treatments in terms primarily of toxicity management but also quality of life and survival in adult cancer patients. Forty-nine trials met the inclusion criteria and were reviewed according to standard processes of systematic reviews. These trials included 3992 patients. All studies with the exception of one were of low methodological quality. The vast majority of the studies have shown that Chinese medicinal herbs improved treatment side effects, quality of life, and performance status, and some have provided evidence of tumour regression and increased survival. While no clinical recommendations can derive from such low quality studies, the number of studies reporting positive results is high enough to suggest that Chinese medicinal herbs may have a role in cancer care. However, more methodologically rigorous studies need to be developed as a priority before any firm conclusions can be drawn. Complement Ther Med. 2009 Apr;17(2):92-120. Epub 2008 Dec 25. (Molassiotis APotrata BCheng KK. 2009)

Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review.

De Grandis D. CNS Drugs. 2007;21 Suppl 1:39-43; discussion 45-6.Divisione di Neurologia, Ospedale Civile di Rovigo, Rovigo, Italy. ddegrandis@iol.it

Abstract

Peripheral neurotoxicity is a major complication associated with the use of chemotherapeutic agents such as platinum compounds, taxanes and vinca alkaloids. The neurotoxicity of chemotherapy depends not only on the anticancer agent(s) used, the cumulative dose and the delivery method, but also on the capacity of the nerve to cope with the nerve-damaging process. The sensory and motor symptoms and signs of neurotoxicity are disabling, and have a significant impact on the quality of life of cancer patients. Moreover, the risk of cumulative toxicity may limit the use of highly effective chemotherapeutic agents. Therefore, prophylaxis and treatment of peripheral neurotoxicity secondary to chemotherapy are major clinical issues. Acetyl-L-carnitine (ALC), the acetyl ester of L-carnitine, plays an essential role in intermediary metabolism. Some of the properties exhibited by ALC include neuroprotective and neurotrophic actions, antioxidant activity, positive actions on mitochondrial metabolism, and stabilisation of intracellular membranes. ALC has demonstrated efficacy and high tolerability in the treatment of neuropathies of various aetiologies, including chemotherapy-induced peripheral neuropathy (CIPN). In several experimental settings, the prophylactic administration of ALC prevented the occurrence of peripheral neurotoxicity commonly induced by chemotherapeutic agents. In animal models of CIPN, ALC administration promoted the recovery of nerve conduction velocity, restored the mechanical nociceptive threshold, and induced analgesia by up-regulating the expression of type-2 metabotropic glutamate receptors in dorsal root ganglia. These results, plus the favourable safety profile of ALC in neuropathies of other aetiologies, have led to the effects of ALC on CIPN being investigated in cancer patients. Preliminary results have confirmed the reasonably good tolerability profile and the efficacy of ALC on CIPN. The present studies support the use of ALC in cancer patients with persisting neurotoxicity induced by paclitaxel or cisplatin treatment.


A pilot study on the effect of acetyl-L-carnitine in paclitaxel- and cisplatin-induced peripheral neuropathy.

Maestri ADe Pasquale Ceratti ACundari SZanna CCortesi ECrinò L. Tumori. 2005 Mar-Apr;91(2):135-8.Medical Oncology Unit, Bellaria Hospital, Bologna, Italy.

Abstract

AIMS AND BACKGROUND: In addition to bone marrow suppression and renal toxicity, neurotoxicity is a commonly occurring side effect of widely used chemotherapeutic agents like taxanes, cisplatin and vinca alkaloids. Neurotoxicity can cause antitumor therapy discontinuation or dose regimen modification. The aim of the present exploratory study was to investigate the activity of acetyl-L-carnitine in reversing peripheral neuropathy in patients with chemotherapy-induced peripheral neuropathy.METHODS AND STUDY DESIGN: Twenty-seven patients (16 males and 11 females) with paclitaxel and/or cisplatin-induced neuropathy (according to WHO recommendations for the grading of acute and subacute toxic effects) were enrolled. Patients received at least one cisplatin- (n = 5) or one paclitaxel- (n = 11) based regimen, or a combination of both (n = 11). Patients with chemotherapy-induced peripheral neuropathy were treated with acetyl-L-carnitine 1 g/die i.v. infusion over 1-2 h for at least 10 days.RESULTS: Twenty-six patients were evaluated for response having completed at least 10 days of acetyl-L-carnitine therapy (median, 14 days; range, 10-20). At least one WHO grade improvement in the peripheral neuropathy severity was shown in 73% of the patients. A case of insomnia related to ALC treatment was reported in one patient. Acetyl-L-carnitine seems to be an effective and well-tolerated agent for the treatment of chemotherapy-induced peripheral neuropathy.CONCLUSIONS: Our preliminary results should be confirmed in double-blind, placebo controlled studies.


Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine.

Bianchi GVitali GCaraceni ARavaglia SCapri GCundari SZanna CGianni L. Eur J Cancer. 2005 Aug;41(12):1746-50.Medical Oncology A, Istituto Nazionale per lo Studio e la Cura dei Tumori, Via Venezian 1, 20133 Milan, Italy.

Abstract

Acetyl-L-carnitine (ALC) improves non-oncological neuropathies. We tested oral ALC (1 g tid) for 8 weeks in 25 patients with neuropathy grade 3 (common toxicity criteria–CTC) during paclitaxel or cisplatin therapy, or grade 2 persisting for at least three months after discontinuing the drugs. An independent neurologist assessed patients before and after ALC. All patients except one reported symptomatic relief, and only two described grade 1 nausea. The sensory neuropathy grade improved in 15 of 25 (60%), and motor neuropathy in 11 of 14 patients (79%). Total neuropathy score (TNS) that included neurophysiological measures improved in 23 (92%). Amelioration of sensory amplitude and conduction velocity (sural and peroneal nerves) was measured in 22 and 21 patients, respectively. Symptomatic improvement persisted in 12 of 13 evaluable patients at median 13 months after ALC. In view of its effect in improving established paclitaxel- and cisplatin-neuropathy, we recommend ALC testing in preventing progression or revert symptoms during neurotoxic chemotherapy.


Acetyl-L-carnitine prevents and reduces paclitaxel-induced painful peripheral neuropathy.

Flatters SJXiao WHBennett GJ. Neurosci Lett. 2006 Apr 24;397(3):219-23. Epub 2006 Jan 6. Department of Anaesthesia, McGill University, Montreal, Que., Canada. sflatters@zeus.bwh.harvard.edu

Abstract

This study examines the potential efficacy of acetyl-L-carnitine (ALC) to prevent and treat paclitaxel-induced pain. Rats received four intraperitoneal (i.p.) injections of 2 mg/kg paclitaxel on alternate days which, following a short delay induced marked mechanical hypersensitivity. Daily administration of ALC (50 mg/kg and 100 mg/kg; p.o.; concurrently with paclitaxel and for 14 days afterwards) prevented the development of paclitaxel-induced pain. This effect was long lasting, for at least 3 weeks after the last dose of ALC. In a separate experiment, daily administration of ALC (100 mg/kg; p.o.; for 10 days) to rats with established paclitaxel-induced pain produced an analgesic effect. This effect dissipated shortly after ALC treatment was withdrawn. We conclude that ALC may be useful in the prevention and treatment of chemotherapy-induced painful peripheral neuropathy.

Cancer and Traditional Chinese Medicine – Treating the Side Effects of Chemo-therapy and Radiation with Traditional Chinese Herbs

Amy K. Hanks
The above studies suggest that when used in conjunction with conventional Western cancer interventions Chinese herbal medicines improve the immune system as measured by levels of T lymphocytes, the monoclonal antibody T1, the T4 to T8 (helper to suppressor) T cell ratio, soluble interleukin- 2 receptors, natural killer cells, lymphokine activated killer cells, leukocytes, platelets, BPC, and immunoglobulin M. Other immunologic parameters that showed apparent improvement included the lymphocyte proliferative response, the interleukin-2 induction response, and macrophage activity. As a caveat, it should be noted that improvements in the immune function of human cancer patients have not been clearly linked to clinically significant benefits such as fewer infections, improvement of symptoms, remission, recurrence, or survival rates, though future research may yield evidence of these effects.
Regardless, Chinese herbal treatment also appeared to improve liver and heart functions, and to moderate clinical side effects ranging from gastrointestinal symptoms and reduced body weight, to oral ulcers and skin rashes. Finally, Chinese herbal medicine showed potential for reducing chemotherapy caused nephrotoxicity, and appeared capable of effectively treating pain related to both Western anticancer interventions and pain caused by the cancer disease process itself. These studies show that a large number of Chinese herbal medicines may be useful in treating the side effects of chemotherapy and radiation therapy. The broad range of cancer types included in this review suggests that these results may be applicable to patients with many different types of cancer: from common carcinomas such as those affecting the lung, breast, and liver to rarer carcinomas such as cancers of the esophagus and nasopharynx.

Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial.

Pace AGiannarelli DGaliè ESavarese ACarpano SDella Giulia MPozzi ASilvani AGaviani PScaioli VJandolo BBove LCognetti F. Neurology. 2010 Mar 2;74(9):762-6.Department of Neuroscience, Regina Elena National Cancer Institute, 00144 Rome, Italy. pace@ifo.it

Abstract

OBJECTIVE: The clinical use of cisplatin chemotherapy is limited by severe peripheral neurotoxicity reported in up to 90% of patients receiving a cumulative dose higher than 300 mg/m(2). The present study evaluates the neuroprotective effect of antioxidant supplementation (vitamin E) in patients treated with cisplatin chemotherapy.METHODS: A total of 108 patients treated with cisplatin chemotherapy were randomly assigned to receive vitamin E supplementation (alpha-tocopherol 400 mg/day) or placebo. Treatment was started orally before chemotherapy and continued for 3 months after the suspension of cisplatin.RESULTS: Of 108 randomized patients, 68 received at least one clinical and neurophysiologic examination after cisplatin CT; 41 patients received a cumulative dose of cisplatin higher than 300 mg/m(2) and were eligible for statistical analysis: 17 in the vitamin E group (group 1) and 24 in the placebo group (group 2). The incidence of neurotoxicity was significantly lower in group 1 (5.9%) than in group 2 (41.7%) (p < 0.01). The severity of neurotoxicity, measured with a validated neurotoxicity score (Total Neuropathy Score [TNS]), was significantly lower in patients receiving vitamin E than those receiving placebo (mean TNS 1.4 vs 4.1; p < 0.01).CONCLUSIONS: This phase III study confirms the neuroprotective role of vitamin E against cisplatin peripheral neurotoxicity. Vitamin E supplementation should be adopted in patients receiving cisplatin-based chemotherapy. Classification of evidence: This study provides Class II evidence that vitamin E supplementation significantly reduces the relative risk of developing signs or symptoms of neurotoxicity (relative risk = 0.14) (95% confidence interval = 0.02-1.00, p < 0.05).


Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation.

A randomized, controlled trial was performed to assess the efficacy and safety of vitamin E supplementation for prophylaxis against paclitaxel-induced peripheral neuropathy (PIPN). Thirty-two patients undergoing six courses of paclitaxel-based chemotherapy were randomly assigned to receive either chemotherapy with vitamin E (300 mg twice a day, Group I) or chemotherapy without vitamin E supplementation (Group II). A detailed neurological examination and electrophysiological study was performed during and 3 months after chemotherapy. The severity of PIPN was summarized by means of a modified Peripheral Neuropathy (PNP) score. The incidence of neurotoxicity differed significantly between groups, occurring in 3/16 (18.7%) patients assigned to the vitamin E supplementation group and in 10/16 (62.5%) controls (P=0.03). The relative risk (RR) of developing PIPN was significantly higher in controls than in vitamin E group patients (RR=0.3, 95% confidence interval (CI)=0.1-0.9). Mean PNP scores were 2.25+/-5.1 (range 0-15) for patients in Group I and 11+/-11.63 (range 0-32) for those in Group II (P=0.01). Vitamin E supplementation was well tolerated and showed an excellent safety profile. This study shows that vitamin E effectively and safely protects patients with cancer from the occurrence of paclitaxel-induced peripheral nerve damage. A double-blind, placebo-controlled trial is needed to confirm these results. J Pain Symptom Manage. 2006 Sep;32(3):237-44. (Argyriou AA, et al 2006)


Ingestion of selenium and other antioxidants during prostate cancer radiotherapy: A good thing?

Tabassum ABristow RGVenkateswaran V. Cancer Treat Rev. 2010 Jan 15. [Epub ahead of print]Molecular and Cellular Biology, Sunnybrook Health Science Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5.Radiation and many chemotherapy agents work to kill cells by inducing free radicals that damage DNA and proteins. Antioxidants such as vitamin E, beta carotene, lycopene, and selenium have been associated with a reduction in cancer risk when ingested by prostate cancer patients. Selenium is a promising agent currently being evaluated as a prostate cancer prevention agent. Selenium is an essential trace element and is involved in antioxidant protection and the redox-regulation in humans. Several adverse effects of radiotherapy and chemotherapy in cancer patients have been linked to oxidative cell processes in the human body. Selenium supplementation may protect healthy tissues and reduce the side effects of treatment. Despite two decades of research into this question, no clear answer has appeared. Therefore, understanding the mechanism(s) by which dietary nutrients exert their effects in prostate carcinogenesis, may lead to the exploitation of new chemoprevention agents. A large body of epidemiological evidence, including observational, trials, and randomized controlled clinical trials, support the proposition that selenium may prevent prostate cancer in humans. These clinical studies are supported by in vitro and in vivo data using prostate cancer models. This systematic review provides the first evidence that antioxidant supplementation during chemotherapy holds potential for reducing dose-limiting toxicities. The pre-clinical and clinical evidence as to whether ingestion of supplemental selenium, in addition to radiotherapy/chemotherapy is beneficial, detrimental or neutral towards patient outcome is also discussed. Copyright © 2009 Elsevier Ltd. All rights reserved.


A randomized controlled trial evaluating the efficacy and safety of vitamin E supplementation for protection against cisplatin-induced peripheral neuropathy: final results.

AIM: A randomized, open label with blind assessment, controlled trial was performed to assess efficacy and adverse-event profile of vitamin E, given as supplementation for prophylaxis against cisplatin-induced peripheral neuropathy (CIPN). PATIENTS AND METHODS: A total of 30 patients scheduled to receive six courses of cumulative cisplatin-based regimens were randomly allocated to treatment and control groups and were then studied by means of neurological examination and electrophysiological study. Patients assigned to group I (n=14) orally received vitamin E at a daily dose of 600 mg/day during chemotherapy and 3 months after its cessation were compared to patients of group II (n=16), who received no vitamin E supplementation and served as controls. The severity of neurotoxicity was summarized by means of a modified Peripheral Neuropathy (PNP) score. RESULTS: The incidence of neurotoxicity differed significantly between groups, occurring in 3/14 (21.4%) of patients assigned to the vitamin E supplementation group and in 11/16 (68.5%) of controls (p=0.026). The relative risk (RR) of developing neurotoxicity was significantly higher in case of controls, RR=2.51, 95% C.I.=1.16-5.47. Mean PNP scores were 4.99+/-1.33 for patients of group I and 10.47+/-10.62 for controls, (p=0.023). None of the adverse events or deaths occurred, were judged as likely to be related to the vitamin E supplementation. CONCLUSION: Vitamin E effectively and safely protects patients with cancer from occurrence of cisplatin neurotoxicity. Support Care Cancer. 2006 Nov;14(11):1134-40. Epub 2006 Apr 19. (Argyriou AA, et al 2006)

Impact of antioxidant supplementation on chemotherapeutic efficacy: a systematic review of the evidence from randomized controlled trials.

Block KIKoch ACMead MNTothy PKNewman RAGyllenhaal C. Cancer Treat Rev. 2007 Aug;33(5):407-18. Epub 2007 Mar 23.Institute for Integrative Cancer Research and Education, 1800 Sherman Avenue, Suite 350, Evanston, IL 60201, USA. kblock@blockmedical.comPURPOSE: Much debate has arisen about whether antioxidant supplementation alters the efficacy of cancer chemotherapy. Some have argued that antioxidants scavenge the reactive oxygen species integral to the activity of certain chemotherapy drugs, thereby diminishing treatment efficacy. Others suggest antioxidants may mitigate toxicity and thus allow for uninterrupted treatment schedules and a reduced need for lowering chemotherapy doses. The objective of this study is to systematically review the literature in order to compile results from randomized trials that evaluate concurrent use of antioxidants with chemotherapy. DESIGN: MEDLINE, Cochrane, CinAhl, AMED, AltHealthWatch and EMBASE databases were searched. Only randomized, controlled clinical trials that reported survival and/or tumor response were included in the final tally. The literature searches were performed in duplicate following a standardized protocol. No meta-analysis was performed due to heterogeneity of tumor types and treatment protocols used in trials that met the inclusion criteria. RESULTS: Of 845 articles considered, 19 trials met the inclusion criteria. Antioxidants evaluated were: glutathione (7), melatonin (4), vitamin A (2), an antioxidant mixture (2), vitamin C (1), N-acetylcysteine (1), vitamin E (1) and ellagic acid (1). Subjects of most studies had advanced or relapsed disease. CONCLUSION: None of the trials reported evidence of significant decreases in efficacy from antioxidant supplementation during chemotherapy. Many of the studies indicated that antioxidant supplementation resulted in either increased survival times, increased tumor responses, or both, as well as fewer toxicities than controls; however, lack of adequate statistical power was a consistent limitation. Large, well-designed studies of antioxidant supplementation concurrent with chemotherapy are warranted.

Protein and ginger for the treatment of chemotherapy-induced delayed nausea.
BACKGROUND: Nausea that develops during the period that begins 24 hours after the administration of chemotherapy is called delayed nausea, and occurs in many patients with cancer. Meals high in protein decrease the nausea of motion sickness and pregnancy, possibly by reducing gastric dysrhythmias. Ginger also has antinausea properties. OBJECTIVES: To explore the use of protein meals with ginger for the treatment of the delayed nausea of chemotherapy. DESIGN: Twenty-eight (28) patients with cancer receiving chemotherapy for the first time were assigned to 1 of 3 groups. For 3 days beginning the day after their chemotherapy, Control Group patients continued with their normal diet, Protein Group patients consumed a protein drink and ginger twice daily, and High Protein Group patients consumed a protein drink with additional protein and ginger twice daily. OUTCOME MEASURES: Patients recorded in a diary each day whether they had experienced nausea, whether their nausea had been frequent, whether their nausea had been bothersome, and whether they had needed any antiemetic medication. Gastric myoelectrical activity was assessed in 5 patients before and after ingestion of a high protein meal and ginger. RESULTS: Reports of nausea, frequent nausea, and bothersome nausea were significantly less common among High Protein Group patients than among Control and Protein Group patients. Furthermore, significantly fewer patients in the High Protein Group used antiemetic medication. Differences between the Protein and Control groups were not statistically significant. In the 5 patients who had tests of gastric myoelectrical activity performed, a significant decrease in gastric dysrhythmia occurred after ingestion of the protein and ginger. CONCLUSIONS: High protein meals with ginger reduced the delayed nausea of chemotherapy and reduced use of antiemetic medications. Protein with ginger holds the potential of representing a novel, nutritionally based treatment for the delayed nausea of chemotherapy. J Altern Complement Med. 2008 Jun;14(5):545-51. (Levine ME, et al 2008)

Effect of citronellol and the Chinese medical herb complex on cellular immunity of cancer patients receiving chemotherapy/radiotherapy.
Leukopenia and immunity impairment usually occur during cancer therapy. Citronellol, an oil soluble compound derived from the geranium, has anticancer and antiinflammatory properties, as well as promoting wound healing. Ganoderma lucidum, Codonopsis pilosula and Angelicae sinensis are traditional Chinese herbs, all of which have proven immunomodulatory functions in laboratory-based research. This randomized, double-blind, placebo-controlled study examined whether the Chinese medicinal herb complex (CCMH; a mixture of citronellol and extracts of G. lucidum, C. pilosula and A. sinensis) improves the immune cell counts of cancer patients receiving chemotherapy and/or radiotherapy. A total of 105 cancer patients receiving chemotherapy or radiotherapy were enrolled. The quantities of immune cells in the blood of the subjects were determined before and after 6 weeks of cancer treatment, with either CCMH or a placebo. CCMH significantly reduced the depletion of leukocytes (14.2% compared with 28.2%) and neutrophils (11.0% compared with 29.1%). Analysis of the lymphocyte phenotype revealed that the patients receiving the placebo had reduced CD4 lymphocytes and natural killer (NK) cells than the CCMH-treated patients. Treatment with CCMH for patients receiving chemotherapy and/or radiotherapy may improve their immune function, improving their ability to fight off the cancer, as well as any secondary infections that could compromise their treatment and their health. Phytother Res. 2009 Jun;23(6):785-90(Zhuang SR, et al 2009).

Antioxidant Supplementation Reduces Incidence Of Cancer in Men
CHICAGO, IL — November 22, 2004 — Low-dose antioxidant supplementation may reduce the risk of cancer among men, but not in women, according to an article in the November 22 issue ofThe Archives of Internal Medicine, one of the JAMA/Archives journals.
According to the article, antioxidants including beta carotene, ascorbic acid, vitamin E, selenium, and zinc may prevent some of the harmful effects caused by free radicals – reactive molecules produced by metabolism in the body. It has also been suggested that a low dietary intake of antioxidants increases the incidence of cancer and cardiovascular disease.
Serge Hercberg, M.D., Ph.D., of the Institute National de la Sante et de la Recherche Medicale (INSERM) and Unite de Surveillance et d’Epidemiologie Nutritionnelle, Paris, and colleagues tested the efficacy of dietary supplementation with a combination of antioxidant vitamins and minerals in reducing the incidence of cancer and cardiovascular disease among 13,017 French adults. There were 7,876 women aged 35 to 60 years old, and 5,141 men ages 45 to 60 years old included in the study. Participants were randomly assigned to take either a daily capsule containing 120 milligrams of ascorbic acid, 30 milligrams of vitamin E, six milligrams of beta carotene, 100 micrograms of selenium, and 20 milligrams of zinc; or a placebo capsule. Participants were followed-up for a median of 7.5 years.
The researchers found no differences between the antioxidant and placebo group in terms of cancer incidence (4.1 percent of the antioxidant group vs. 4.5 percent of the placebo group), or in cardiovascular disease incidence (2.1 percent for the antioxidant group vs. 2.1 percent for the placebo group) or all-cause death (1.2 percent for the antioxidant group vs. 1.5 percent for the placebo group).
However, when the researchers looked at cancer incidence according to sex, they found a significant protective effect of the antioxidants in men, who were 31 percent less likely to develop cancer than women. A similar trend was seen in men for death rates.
“After 7.5 years, low-dose antioxidant supplementation lowered total cancer incidence and all-cause mortality in men but not in women. Supplementation may be effective in men only because of their lower baseline status of certain antioxidants, especially of beta carotene,” the researchers write.
The authors conclude: “… our results suggest that an adequate and well-balanced supplementation of antioxidant nutrients, at doses that might be reached with a healthy diet that includes a high consumption of fruits and vegetables, had protective effects against cancer in men.”


Oral glutamine for the prevention of chemotherapy-induced peripheral neuropathy.

Amara S. Ann Pharmacother. 2008 Oct;42(10):1481-5. Epub 2008 Aug 12.Pharmacy Department, Saint Barnabas Medical Center, 94 Old Short Hills Rd., Livingston, NJ 07039, USA. samara@sbhcs.com

Abstract

OBJECTIVE: To evaluate the role of glutamine in the reduction of peripheral neuropathy associated with neurotoxic chemotherapy.DATA SOURCES: Relevant literature was accessed through PubMed (1990-May 2008), using the search terms glutamine, chemotherapy, peripheral neuropathy, neurotoxicity, safety, paclitaxel, platinum compounds, and vinca alkaloids. References in the identified articles were also reviewed for pertinent information.STUDY SELECTION AND DATA EXTRACTION: Studies evaluating the role of oral glutamine for prevention and treatment of chemotherapy-induced peripheral neuropathy (CIPN) were included. Studies regarding the role of glutamine in the reduction of other radiation- and chemotherapy-related toxicities, such as mucositis, cardiotoxicity, diarrhea, and cachexia, were excluded.DATA SYNTHESIS: CIPN is a significant adverse effect associated with neurotoxic chemotherapy, particularly with taxanes, platinum compounds, and vinca alkaloids. There is no standard therapy for the treatment of this dose-limiting reaction. Glutamine is a nonessential amino acid that is thought to have a neuroprotective role, possibly due to the upregulation of nerve growth factor. Two studies revealed that oral glutamine was effective in reducing peripheral neuropathy associated with high-dose paclitaxel, as evidenced by a reduction in numbness, dysesthesias, and motor weakness, as well as a smaller loss of vibratory sensation. Another study found that glutamine effectively reduced peripheral neuropathy in patients with colorectal cancer being treated with oxaliplatin, thereby decreasing the need for an oxaliplatin dose reduction. However, data are limited by small sample sizes in these studies and the lack of placebo-controlled, randomized clinical trials.CONCLUSIONS: Larger, well-designed, placebo-controlled trials assessing both safety and efficacy of oral glutamine are warranted before this agent can be definitively recommended for the prevention of CIPN in patients treated with high-dose paclitaxel or oxaliplatin.


Antioxidants and other nutrients do not interfere with chemotherapy or radiation therapy and can increase kill and increase survival, part 1.

Simone CB 2ndSimone NLSimone VSimone CB. Altern Ther Health Med. 2007 Jan-Feb;13(1):22-8.Simone Protective Cancer Institute in Lawrenceville, NJ, USA.

Abstract

PURPOSE: Some in the oncology community contend that patients undergoing chemotherapy and/or radiation therapy should not use food supplement antioxidants and other nutrients. Oncologists at an influential oncology institution contended that antioxidants interfere with radiation and some chemotherapies because those modalities kill by generating free radicals that are neutralized by antioxidants, and that folic acid interferes with methotrexate. This is despite the common use of amifostine and dexrazoxane, 2 prescription antioxidants, during chemotherapy and/or radiation therapy.DESIGN: To assess all evidence concerning antioxidant and other nutrients used concomitantly with chemotherapy and/or radiation therapy, the MEDLINE and CANCERLIT databases were searched from 1965 to November 2003 using the words vitamins, antioxidants, chemotherapy, and radiation therapy. Bibliographies of articles were searched. All studies reporting concomitant nutrient use with chemotherapy and/or radiation therapy (280 peer-reviewed articles including 62 in vitro and 218 in vivo) were indiscriminately included.RESULTS: Fifty human clinical randomized or observational trials have been conducted, involving 8,521 patients using beta-carotene; vitamins A, C, and E; selenium; cysteine; B vitamins; vitamin D3; vitamin K3; and glutathione as single agents or in combination.CONCLUSIONS: Since the 1970s, 280 peer-reviewed in vitro and in vivo studies, including 50 human studies involving 8,521 patients, 5,081 of whom were given nutrients, have consistently shown that non-prescription antioxidants and other nutrients do not interfere with therapeutic modalities for cancer. Furthermore, they enhance the killing of therapeutic modalities for cancer, decrease their side effects, and protect normal tissue. In 15 human studies, 3,738 patients who took non-prescription antioxidants and other nutrients actually had increased survival.


Mistletoe therapy in oncology.

Horneber MABueschel GHuber RLinde KRostock M. Cochrane Database Syst Rev. 2008 Apr 16;(2):CD003297.Medizinische Klinik 5, Arbeitsgruppe Biologische Krebstherapie, Prof.-Ernst-Nathan-Str. 1, Nuernberg, Germany, D-90419. horneber@klinikum-nuernberg.de

Abstract

BACKGROUND: Mistletoe extracts are commonly used in cancer patients. It is claimed that they improve survival and quality of life (QOL) in cancer patients.OBJECTIVES: To determine the effectiveness, tolerability and safety of mistletoe extracts given either as monotherapy or adjunct therapy for patients with cancer.SEARCH STRATEGY: Search sources included the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2007) Cochrane Complementary Medicine Field Registry of randomized clinical trials (RCTs) and controlled clinical trials, MEDLINE, EMBASE, HEALTHSTAR, INT. HEALTH TECHNOLOGY ASSESSMENT, SOMED, AMED, BIOETHICSLINE, BIOSIS, CancerLit, CATLINE, CISCOM (August 2007). For the search the Standard Operating Procedures of the Information System in Health Economics at the German Institute for Medical Documentation and Information (DIMDI) were utilized. Reference lists of relevant articles and authors extensive files were searched for additional studies. Manufacturers of mistletoe preparations were contacted.SELECTION CRITERIA: We included RCTs of adults with cancer of any type. The interventions were mistletoe extracts as sole treatments or given concomitantly with chemo- or radiotherapy. The outcome measures were survival times, tumor response, QOL, psychological distress, adverse effects from antineoplastic treatment and safety of mistletoe extracts.DATA COLLECTION AND ANALYSIS: Three review authors independently assessed trials for inclusion in the review. All review authors independently took part in the extraction of data and assessment of study quality and clinical relevance. Disagreements were resolved by consensus. Study authors were contacted where information was unclear. Methodological quality was narratively described and additionally assessed with the Delphi list and the Jadad score. High methodological quality was defined if six out of nine Delphi criteria, or four out of five Jadad criteria were fulfilled. Results were presented qualitatively.MAIN RESULTS: Eighty studies were identified. Fifty-eight were excluded for various reasons, usually as there was no prospective trial design with randomised treatment allocation. Of the 21 included studies 13 provided data on survival, 7 on tumour response, 16 on measures of QOL or psychological outcomes, or prevalence of chemotherapy-related adverse effects and 12 on side effects of mistletoe treatment; overall comprising 3484 randomised cancer patients. Interventions evaluated were 5 preparations of mistletoe extracts from 5 manufacturers and one commercially not available preparation. The general reporting of RCTs was poor. Of the 13 trials investigating survival, 6 showed some evidence of a benefit, but none of them was of high methodological quality. The results of two trials in patients with melanoma and head and neck cancer gave some evidence that the used mistletoe extracts are not effective for improving survival. Of the 16 trials investigating the efficacy of mistletoe extracts for either improving QOL, psychological measures, performance index, symptom scales or the reduction of adverse effects of chemotherapy, 14 showed some evidence of a benefit, but only 2 of them including breast cancer patients during chemotherapy were of higher methodological quality. Data on side effects indicated that, depending on the dose, mistletoe extracts were usually well tolerated and had few side effects.AUTHORS’ CONCLUSIONS: The evidence from RCTs to support the view that the application of mistletoe extracts has impact on survival or leads to an improved ability to fight cancer or to withstand anticancer treatments is weak. Nevertheless, there is some evidence that mistletoe extracts may offer benefits on measures of QOL during chemotherapy for breast cancer, but these results need replication. Overall, more high quality, independent clinical research is needed to truly assess the safety and effectiveness of mistletoe extracts. Patients receiving mistletoe therapy should be encouraged to take part in future trails.

6.  Hepatocellular Cancer

Traditional Chinese Medicines in the treatment of hepatocellular cancers: a systematic review and meta-analysis.

Wu PDugoua JJEyawo OMills EJ. J Exp Clin Cancer Res. 2009 Aug 12;28:112. Shanghai Hospital /#4, Shanghai, PR China. pwu@ccnm.edu

Abstract

BACKGROUND: Liver cancer is a common malignancy with a high mortality rate. Given the poor prognosis associated with this cancer, many patients seek additional therapies that may improve quality of life or survival. Several Traditional Chinese Medicines (TCM) have been evaluated in clinical trials, but little is known about them outside of China.METHODS: We searched independently and in duplicate 8 electronic databases, including 2 Chinese language databases, until February 2009. We included any randomized clinical trials (RCT) evaluating a TCM oral preparation for the treatment of hepatocellular cancers. We abstracted data on survival, tumor response, and performance scores. We conducted a random-effects meta-analysis and applied a meta-regression analysis.RESULTS: We included 45 RCTs (n = 3,236). All studies employed an active control group. In general, the reporting of methodological issues was poor. We analyzed data from 37 trials reporting on complete response effects score (Relative Risk [RR] of 1.26 (95 CI, 1.04-1.52, P = 0.01, I2 = 0%, P = 0.99). Products containing ginseng, astragalus and mylabris had a larger treatment effect (OR 1.34, 95% CI, 1.04-1.71, P = 0.01) than the pooled broad estimate, also the case for astragalus-based treatments (OR 1.35, 95% CI, 1.001-1.80. P = 0.048). We examined survival rates and pooled 15 studies reporting on 6 month outcomes (RR 1.10, 95% CI, 1.04-1.15, P = < 0.0001, I2 = 0%, P = 0.60). This effect was consistent at other prospective dates, including 12 months (22 trials, RR 1.26, 95% CI, 1.17-1.36, P = < 0.0001, I2 = 7%, P = 0.36), 24 months (15 trials, 1.72, 95% CI, 1.40-2.03, P = < 0.0001, I2 = 0%, P = 0.75); and, at 36 months (8 trials, RR 2.40, 95% CI, 1.65-3.49, P = < 0.0001, I2 = 0%, P = 0.62).LIMITATIONS: All included trials were conducted in China where emerging evidence suggests many RCTs are not, in fact, randomized. Publication bias may exist, favouring positive reports.CONCLUSION: Our meta-analysis displays compelling evidence of effectiveness for hepatocellular cancers that should be evaluated in high-quality and transparent clinical trials.


Chinese herbal medicine and chemotherapy in the treatment of hepatocellular carcinoma: a meta-analysis of randomized controlled trials.

Shu XMcCulloch MXiao HBroffman MGao J. Integr Cancer Ther. 2005 Sep;4(3):219-29.Pine Street Foundation, San Anselmo, CA 94960, USA.

Abstract

BACKGROUND: Hepatocellular carcinoma (HCC), one of the most common malignancies worldwide, is highly resistant to standard therapy. It is unclear whether chemotherapy, arterial embolization, or arterial chemoembolization improve survival advantage enough to justify their high toxicity. Treatment with Chinese herbal medicine has been explored, combining herbs that stimulate host immune response with those that have cytotoxic activity against HCC cells. The authors sought to evaluate the effectiveness of Chinese herbal medicine combined with chemotherapy. The hypothesis was that Chinese herbal medicine added to chemotherapy for the treatment of HCC would improve survival and tumor response, when compared to treatment with chemotherapy alone.METHODS: The authors searched the databases TCMLARS, PubMed, and EMBASE as well as the bibliographies of studies identified in the systematic search for potentially relevant titles or abstracts of studies in any language. They retained those that (1) treated only HCC patients, (2) were described as randomized or reported that there was no statistical difference between treatment groups, (3) gave patients either Chinese herbal medicine therapy combined with chemotherapy in the treatment group or chemotherapy alone in the control group, and (4) provided data on the number of enrolled subjects and responders and nonresponders for tumor response and survival. The authors used random effects meta-analysis to combine data.RESULTS: Twenty-six studies representing 2079 patients met the inclusion criteria. Chinese herbal medicine combined with chemotherapy, compared to chemotherapy alone, improved survival at 12 months (relative risk [RR], 1.55; 95% confidence interval [CI], 1.39-1.72; P < .000), 24 months (RR, 2.15; 95% CI, 1.75-2.64; P < .000), and 36 months (RR, 2.76; 95% CI, 1.95-3.91; P < .000). Tumor response increased (RR, 1.39; 95% CI, 1.24-1.56; P < .000).CONCLUSIONS: These findings provide promising evidence that combining Chinese herbal medicine with chemotherapy may benefit patients with HCC. Because of the low quality of these studies, these findings should be confirmed through conducting high-quality, rigorously controlled trials.

7.  Non-Hodgkin’s Lymphoma

High-dose sodium selenite can induce apoptosis of lymphoma cells in adult patients with non-Hodgkin’s lymphoma.

Asfour IAEl-Tehewi MMAhmed MHAbdel-Sattar MAMoustafa NNHegab HMFathey OM. Biol Trace Elem Res. 2009 Mar;127(3):200-10. Epub 2008 Oct 25.Department of Internal Medicine and Clinical Hematology, Clinical Hematology Unit, Ain-Shams Faculty of Medicine, Ain-Shams University, Cairo, Egypt.

Abstract

The present study was undertaken to explore the effect of administration of high doses of sodium selenite on the apoptosis of lymphoma cells in patients with non-Hodgkin’s lymphoma (NHL). Forty patients with newly diagnosed NHL were randomly divided into two groups. Group I received standard chemotherapy, whereas group II received adjuvant sodium selenite 0.2 mg kg(-1) day(-1) for 7 days in addition to chemotherapy. Flow cytometry was used for monitoring of lymphoma cells apoptosis at the time of diagnosis and after therapy in the two groups. Sodium selenite administration resulted in significant increase in percentage of apoptotic lymphoma cells after therapy in group II (78.9 +/- 13.3% versus 58.9 +/- 18.9%, p < 0.05). In addition, patients who received sodium selenite treatment demonstrated statistically significant increase in percentage of reduction of cervical and axillary lymphadenopathy, decrease in splenic size, and decreased percentage of bone marrow infiltration. Also, we found a statistically significant decrease in cardiac ejection fraction (CEF) in group I and no reduction in CEF in patients who received sodium selenite ‘group II’, denoting the cardioprotective effect of selenium. It is concluded that sodium selenite administration at the dosage and duration chosen has synergistic effect to chemotherapy in inducing apoptosis and, consequently, could improve clinical outcome.

8.  Non-Small Cell Lung Cancer
Astragalus-based Chinese herbs and platinum-based chemotherapy for advanced non-small-cell lung cancer: meta-analysis of randomized trials.
PURPOSE: Systemic treatments for advanced non-small-cell lung cancer have low efficacy and high toxicity. Some Chinese herbal medicines have been reported to increase chemotherapy efficacy and reduce toxicity. In particular, Astragalus has been shown to have immunologic benefits by stimulating macrophage and natural killer cell activity and inhibiting T-helper cell type 2 cytokines. Many published studies have assessed the use of Astragalus and other Chinese herbal medicines in combination with chemotherapy. We sought to evaluate evidence from randomized trials that Astragalus-based Chinese herbal medicine combined with platinum-based chemotherapy (versus platinum-based chemotherapy alone) improves survival, increases tumor response, improves performance status, or reduces chemotherapy toxicity. METHODS: We searched CBM, MEDLINE, TCMLARS, EMBASE, Cochrane Library, and CCRCT databases for studies in any language. We grouped studies using the same herbal combinations for random-effects meta-analysis. RESULTS: Of 1,305 potentially relevant publications, 34 randomized studies representing 2,815 patients met inclusion criteria. Twelve studies (n = 940 patients) reported reduced risk of death at 12 months (risk ratio [RR] = 0.67; 95% CI, 0.52 to 0.87). Thirty studies (n = 2,472) reported improved tumor response data (RR = 1.34; 95% CI, 1.24 to 1.46). In subgroup analyses, Jin Fu Kang in two studies (n = 221 patients) reduced risk of death at 24 months (RR = 0.58; 95% CI, 0.49 to 0.68) and in three studies (n = 411) increased tumor response (RR = 1.76; 95% CI, 1.23 to 2.53). Ai Di injection (four studies; n = 257) stabilized or improved Karnofsky performance status (RR = 1.28; 95% CI, 1.12 to 1.46). CONCLUSION: Astragalus-based Chinese herbal medicine may increase effectiveness of platinum-based chemotherapy when combined with chemotherapy. These results require confirmation with rigorously controlled trials. J Clin Oncol. 2006 Jan 20;24(3):419-30. (McCulloch M, et al 2006)

Safety and pharmacokinetic trial of docetaxel plus an Astragalus-based herbal formula for non-small cell lung cancer patients.
PURPOSE: To study a commonly used Astragalus-based herbal formula previously found effective in non-small cell lung cancer (NSCLC) on the pharmacokinetics of docetaxel in patients with NSCLC. METHODS: Patients with advanced NSCLC who progressed after prior platinum-containing chemotherapy were accrued and received docetaxel at 35 mg/m(2) for 3 weeks followed by 1 week of rest. At 4 days prior to the second dosing, Jinfukang was given orally. Pharmacokinetic studies of initial-dose docetaxel (in the absence of Jinfukang) and the third dose (in the presence of Jinfukang) were compared. RESULTS: Of the 24 patients enrolled, 21 started Jinfukang and docetaxel. Jinfukang had no significant impact on the pharmacokinetics of docetaxel. Median time to progression or withdrawal from treatment was 7 weeks. Twelve patients were removed from study for progression of disease; nine patients withdrew. CONCLUSIONS: Jinfukang did not alter the pharmacokinetics of docetaxel nor appear to affect survival in this study. Cancer Chemother Pharmacol. 2009 Dec;65(1):67-71. Epub 2009 May 7. (Cassileth BR, et al 2009)


Oral Chinese herbal medicine (CHM) as an adjuvant treatment during chemotherapy for non-small cell lung cancer: A systematic review.

Chen SFlower ARitchie ALiu JMolassiotis AYu HLewith G. Lung Cancer. 2010 May;68(2):137-45. Epub 2009 Dec 16.School of Medicine, University of Southampton, Southampton, UK.

Abstract

BACKGROUND: Non-small cell lung cancer (NSCLC) remains a major global health problem because of its prevalence and poor prognosis. Treatment options are limited and there is a need to explore alternatives. This systematic review evaluates the role of Chinese herbal medicine (CHM) in association with chemotherapy for NSCLC.METHODS: English and Chinese databases were searched for RCTs comparing CHM with conventional biomedical treatment or placebo. Papers were reviewed systematically and data were analysed using standard Cochrane software Revman 5. RESULTS: Fifteen Chinese trials involving 862 participants met the inclusion criteria. All trials were of poor quality with a considerable risk of bias. There was a significant improvement in quality of life (QoL) (increased Karnofsky Performance Status)

9.  Ovarian Cancer
Tea consumption and ovarian cancer risk in a population-based cohort.
BACKGROUND: Substantial evidence from laboratory studies indicates that green and black tea preparations may protect against various cancers. Few epidemiologic studies, however, have examined the relationship specifically between tea consumption and risk of ovarian cancer. METHODS: We prospectively examined the association between tea consumption and risk of ovarian cancer in 61,057 women aged 40 to 76 years who were participants in the population-based Swedish Mammography Cohort. Participants completed a validated 67-item food frequency questionnaire at enrollment between 1987 and 1990 and were followed for cancer incidence through December 2004. RESULTS: During an average follow-up of 15.1 years, 301 incident cases of invasive epithelial ovarian cancer were ascertained. Tea consumption was inversely associated with the risk of ovarian cancer after controlling for potential confounders (P for trend, .03). Compared with women who never or seldom (less than monthly) consumed tea, the multivariate hazard ratios for those who consumed less than 1 cup per day, 1 cup per day, and 2 or more cups per day were 0.82 (95% confidence interval [CI], 0.62-1.08), 0.76 (95% CI, 0.56-1.04), and 0.54 (95% CI, 0.31-0.91), respectively. Each additional cup of tea per day was associated with an 18% lower risk of ovarian cancer (multivariate hazard ratio, 0.82; 95% CI, 0.68-0.99). CONCLUSION: These results suggest that tea consumption is associated with a reduced risk of epithelial ovarian cancer in a dose-response manner. Arch Intern Med. 2005 Dec 12-26;165(22):2683-6.(Larsson SCWolk A.2005)

Effect of a combination of extract from several plants on cell-mediated and humoral immunity of patients with advanced ovarian cancer.

The influence of a plant preparation AdMax (Nulab Inc., Clearwater, FL, USA) on immunity in ovarian cancer patients was studied. The preparation is a combination of dried ethanol/water extracts from roots of Leuzea carthamoides, Rhodiola rosea, Eleutherococcus senticosus and fruits of Schizandra chinensis. Twenty eight patients with stage III-IV epithelial ovarian cancer were treated once with 75 mg/m(2) cisplatin and 600 mg/m(2) cyclophosphamide. Peripheral blood was collected 4 weeks after the chemotherapy. Subclasses of T, B and NK lymphocytes were tested for in the blood samples: CD3, CD4, CD5, CD7, CD8, CD11B, CD16, CD20, CD25, CD38, CD45RA, CD50, CD71 and CD95. Immunoglobulin G, A and M concentrations were also determined. Changes were observed in the following T cell subclasses: CD3, CD4, CD5 and CD8. In patients who took AdMax (270 mg a day) for 4 weeks following the chemotherapy, the mean numbers of the four T cell subclasses were increased in comparison with the mean numbers of the T cell subclasses in patients who did not take AdMax. In patients who took AdMax, the mean amounts of IgG and IgM were also increased. The obtained results suggest that the combination of extracts from adaptogenic plants may boost the suppressed immunity in ovarian cancer patients who are subject to chemotherapy. Phytother Res. 2006 May;20(5):424-5. (Kormosh NLaktionov KAntoshechkina M.2006)

Green tea consumption enhances survival of epithelial ovarian cancer.
Our study investigates whether tea consumption can enhance the survival of patients with epithelial ovarian cancer, a prospective cohort study was conducted in Hangzhou, China. The cohort comprised 254 patients recruited during 1999-2000 with histopathologically confirmed epithelial ovarian cancer and was followed up for a minimum of 3 years. Two hundred forty four (96.1%) of the cohort or their close relatives were traced. The variables examined included their survival time and the frequency and quantity of tea consumed post-diagnosis. The actual number of deaths was obtained and Cox proportional hazards models were used to obtain hazard ratios and associated 95% confidence intervals (CI), adjusting for age at diagnosis, locality, BMI, parity, FIGO stage, histologic grade of differentiation, cytology of ascites, residual tumour and chemotherapeutic status. The survival experience was different between tea drinkers and non-drinkers (p < 0.001). There were 81 (77.9%) of 104 tea-drinkers who survived to the time of interview, compared to only 67 women (47.9%) still alive among the 140 non-drinkers. Compared to non-drinkers, the adjusted hazard ratios were 0.55 (95% CI = 0.34-0.90) for tea-drinkers, 0.43 (95% CI = 0.20-0.92) for consuming at least 1 cup of green tea/day, 0.44 (95% CI = 0.22-0.90) for brewing 1 batch or more of green tea/day, 0.40 (95% CI = 0.18-0.90) for consuming more than 500 g of dried tea leaves/year, and 0.38 (95% CI = 0.15-0.97) for consuming at least 2 g of dried tea leaves/batch. The corresponding dose-response relationships were significant (p < 0.05). We conclude that increasing the consumption of green tea post-diagnosis may enhance epithelial ovarian cancer survival.Int J Cancer. 2004 Nov 10;112(3):465-9. (Zhang M, et al 2004)

10.  Pancreatic Cancer

Phase II trial of curcumin in patients with advanced pancreatic cancer.

PURPOSE: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration-approved therapies for it, gemcitabine and erlotinib, produce objective responses in <10% of patients. We evaluated the clinical biological effects of curcumin (diferuloyl-methane), a plant-derived dietary ingredient with potent nuclear factor-kappaB (NF-kappaB) and tumor inhibitory properties, against advanced pancreatic cancer. EXPERIMENTAL DESIGN: Patients received 8 g curcumin by mouth daily until disease progression, with restaging every 2 months. Serum cytokine levels for interleukin (IL)-6, IL-8, IL-10, and IL-1 receptor antagonists and peripheral blood mononuclear cell expression of NF-kappaB and cyclooxygenase-2 were monitored. RESULTS: Twenty-five patients were enrolled, with 21 evaluable for response. Circulating curcumin was detectable as drug in glucuronide and sulfate conjugate forms, albeit at low steady-state levels, suggesting poor oral bioavailability. Two patients showed clinical biological activity. One had ongoing stable disease for >18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappaB, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks. CONCLUSIONS: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer. Clin Cancer Res. 2008 Jul 15;14(14):4491-9. Comment in: Clin Cancer Res. 2009 Jan 15;15(2):747; author reply 747.  (Dhillon N, et al 2008)


Is there a role for herbal medicine in the treatment of pancreatic cancer?. Highlights from the “44th ASCO Annual Meeting”. Chicago, IL, USA. May 30 – June 3, 2008.

Saif MW. JOP. 2008 Jul 10;9(4):403-7.Medical Oncology, Yale University School of Medicine. New Haven, CT, USA. wasif.saif@yale.edu

Abstract

One of the greatest challenges in the treatment of pancreatic cancer remains its inherent lack of beneficial response to cytotoxic chemotherapy. According to the encyclopedic knowledge on herbal medicine regimen and clinical experience accumulated for centuries, traditional Chinese medicine can provide new avenues for alternative treatments of pancreatic diseases. Chinese herbal extracts have been widely used for the treatment of various cancers, but objective information on their efficacy in pancreatic cancer is lacking. This article provides a summary of herbal medicine, presented at the Annual Meeting of ASCO, 2008. The clinical applications of these active compounds warrant further investigation in randomized, controlled clinical trials.


Methionine and vitamin B6 intake and risk of pancreatic cancer: a prospective study of Swedish women and men.

Larsson SCGiovannucci EWolk A. Gastroenterology. 2007 Jan;132(1):113-8. Epub 2006 Oct 12.Division of Nutritional Epidemiology, National Institute of Environmental Medicine, Karolinska Institutet, SE-17177 Stockholm, Sweden. susanna.larson@ki.se

Abstract

BACKGROUND & AIMS: It has been hypothesized that dietary factors involved in methyl group metabolism, such as methionine, folate, and vitamin B(6), may modify cancer risk. We have previously reported an inverse association between folate intake and pancreatic cancer risk in a prospective population-based cohort of Swedish women and men. In the present study, we used data from this prospective study to examine whether methionine and vitamin B(6) intakes were associated with the incidence of exocrine pancreatic cancer.METHODS: Our study population comprised 81,922 Swedish women and men, aged 45-83 years, who were free from cancer and completed a self-administered food-frequency questionnaire in 1997. We used Cox proportional hazards models to estimate rate ratios with 95% confidence intervals (CI), adjusted for age, sex, education, smoking, body mass index, diabetes, and intakes of total energy and dietary folate.RESULTS: During a mean follow-up of 7.2 years, through June 2005, 147 incident cases of pancreatic cancer were diagnosed. Methionine intake was significantly inversely associated with risk of pancreatic cancer, whereas no significant association was observed for dietary or total vitamin B(6) intake. The multivariate rate ratios comparing the highest with the lowest quartile of methionine intake were 0.44 (95% CI, 0.26-0.73; P for trend = .0005) in women and men combined, 0.59 (95% CI, 0.28-1.21; P for trend = .07) in women, and 0.32 (95% CI, 0.15-0.65; P for trend = .002) in men.CONCLUSIONS: These findings suggest that higher methionine intake may reduce the risk of pancreatic cancer.

 11.  Prostate Cancer
  1. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer.
  2. Cancer chemoprevention by pomegranate: laboratory and clinical evidence.
  3.  Lycopene and soy isoflavones in the treatment of prostate cancer.
  4. Is there a benefit from lycopene supplementation in men with prostate cancer? A systematic review.
  5. Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study.
  6. A combination of tomato and soy products for men with recurring prostate cancer and rising prostate specific antigen.
  7. Tea and lycopene protect against prostate cancer.
  8. Whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH) and healthy male inhabitants (HMI) and prostatic tissue selenium levels (PTSL) in patients with PC and BPH.
  9. Serum and dietary vitamin E in relation to prostate cancer risk.

Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer.

Pantuck AJLeppert JTZomorodian NAronson WHong JBarnard RJSeeram NLiker HWang HElashoff RHeber DAviram MIgnarro LBelldegrun A. Clin Cancer Res. 2006 Jul 1;12(13):4018-26. Department of Urology, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, California 90095-1738, USA. apantuck@mednet.ucla.edu

Abstract

PURPOSE: Phytochemicals in plants may have cancer preventive benefits through antioxidation and via gene-nutrient interactions. We sought to determine the effects of pomegranate juice (a major source of antioxidants) consumption on prostate-specific antigen (PSA) progression in men with a rising PSA following primary therapy.EXPERIMENTAL DESIGN: A phase II, Simon two-stage clinical trial for men with rising PSA after surgery or radiotherapy was conducted. Eligible patients had a detectable PSA > 0.2 and < 5 ng/mL and Gleason score < or = 7. Patients were treated with 8 ounces of pomegranate juice daily (Wonderful variety, 570 mg total polyphenol gallic acid equivalents) until disease progression. Clinical end points included safety and effect on serum PSA, serum-induced proliferation and apoptosis of LNCaP cells, serum lipid peroxidation, and serum nitric oxide levels.RESULTS: The study was fully accrued after efficacy criteria were met. There were no serious adverse events reported and the treatment was well tolerated. Mean PSA doubling time significantly increased with treatment from a mean of 15 months at baseline to 54 months posttreatment (P < 0.001). In vitro assays comparing pretreatment and posttreatment patient serum on the growth of LNCaP showed a 12% decrease in cell proliferation and a 17% increase in apoptosis (P = 0.0048 and 0.0004, respectively), a 23% increase in serum nitric oxide (P = 0.0085), and significant (P < 0.02) reductions in oxidative state and sensitivity to oxidation of serum lipids after versus before pomegranate juice consumption.CONCLUSIONS: We report the first clinical trial of pomegranate juice in patients with prostate cancer. The statistically significant prolongation of PSA doubling time, coupled with corresponding laboratory effects on prostate cancer in vitro cell proliferation and apoptosis as well as oxidative stress, warrant further testing in a placebo-controlled study.


Cancer chemoprevention by pomegranate: laboratory and clinical evidence.

Adhami VMKhan NMukhtar H. Nutr Cancer. 2009 Nov;61(6):811-5.Department of Dermatology, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

Abstract

Pomegranate fruit from the tree Punica granatum has been dubbed as the “nature’s power fruit.” Dating back to Biblical times, the tree itself is attributed to possess extraordinary medicinal properties. The geographical distribution of the tree, being native to the Middle East and some Asian countries, is generally attributed to a lack of interest in its medicinal properties by many western scientists. However, the unique biochemical composition of the pomegranate fruit being rich in antioxidant tannins and flavonoids has recently drawn attention of many investigators to study its exceptional healing qualities. Recent research has shown that pomegranate extracts selectively inhibit the growth of breast, prostate, colon and lung cancer cells in culture. In preclinical animal studies, oral consumption of pomegranate extract inhibited growth of lung, skin, colon and prostate tumors. An initial phase II clinical trial of pomegranate juice in patients with prostate cancer reported significant prolongation of prostate specific antigen doubling time. This review focuses on recent investigations into the effects of pomegranate fruit on cancer.


Is there a benefit from lycopene supplementation in men with prostate cancer? A systematic review.

Haseen FCantwell MMO’Sullivan JMMurray LJ. Prostate Cancer Prostatic Dis. 2009;12(4):325-32. Epub 2009 Sep 1.Cancer Epidemiology and Prevention Research Group, Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland, UK. fhaseen01@qub.ac.uk

Abstract

Lycopene has a chemopreventive effect against prostate cancer but its role in prostate cancer progression is unknown; many patients increase their intake of lycopene, although there are no evidence-based guidelines to suggest an effect. Our objective was to conduct a systematic review of literature to evaluate the association between lycopene intake and prostate cancer progression. MEDLINE, EMBASE CINAHL Plus, Web of Science, AMED and CENTRAL databases were systematically searched using terms for lycopene and prostate cancer progression to identify studies published before January 2009. Eight intervention studies were identified (five with no control group; one with an unmatched control group; and two randomized controlled trials (RCTs)).An inverse association was observed between lycopene intake and PSA levels in six studies. The rates of progression measured by bone scan in one RCT were lower in the intervention group. Lycopene resulted in lowering cancer-related symptoms (pain, urinary tract symptoms), and severe toxicity or intolerance was not evident. However, the evidence available to date is insufficient to draw a firm conclusion with respect to lycopene supplementation in prostate cancer patients and larger RCTs are required in broader patient groups.


Lycopene and soy isoflavones in the treatment of prostate cancer.

Vaishampayan UHussain MBanerjee MSeren SSarkar FHFontana JForman JDCher MLPowell IPontes JEKucuk O. Nutr Cancer. 2007;59(1):1-7.Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.

Abstract

Dietary intake of lycopene and soy has been associated with a lower risk of prostate cancer. In vitro studies with lycopene and genistein, a soy isoflavone, have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines. In a previous Phase II clinical trial in prostate cancer patients, we observed prostate-specific antigen (PSA) stabilization with soy isoflavone intake. In this Phase II clinical trial, we investigated the efficacy of lycopene alone or in combination with soy isoflavones on serum PSA levels in men with prostate cancer. To be eligible for the study, men with prostate cancer had to have rising serum PSA following local therapy or while on hormone therapy. Study population included 71 eligible patients who had 3 successive rising PSA levels or a minimum PSA of 10 ng/ml at 2 successive evaluations prior to starting therapy. Subjects were randomly assigned to receive a tomato extract capsule containing 15 mg of lycopene alone (n = 38) or together with a capsule containing 40 mg of a soy isoflavone mixture (n = 33) twice daily orally for a maximum of 6 mo. One patient on the lycopene arm did not receive therapy due to his inability to ingest the study pill. There was no decline in serum PSA in either group qualifying for a partial or complete response. However, 35 of 37 (95%) evaluable patients in the lycopene group and 22 of 33 (67%) evaluable patients in the lycopene plus soy isoflavone group achieved stable disease described as stabilization in serum PSA level. The data suggest that lycopene and soy isoflavones have activity in prostate cancer patients with PSA relapse disease and may delay progression of both hormone-refractory and hormone-sensitive prostate cancer. However, there may not be an additive effect between the 2 compounds when taken together. Future studies are warranted to further investigate the efficacy of lycopene and soy isoflavones in prostate cancer as well as the mechanism of potential negative interaction between them.

Chemoprevention of human prostate cancer by oral administration of green tea catechins in volunteers with high-grade prostate intraepithelial neoplasia: a preliminary report from a one-year proof-of-principle study.
Green tea catechins (GTCs) proved to be effective in inhibiting cancer growth in several experimental models. Recent studies showed that 30% of men with high-grade prostate intraepithelial neoplasia (HG-PIN) would develop prostate cancer (CaP) within 1 year after repeated biopsy. This prompted us to do a proof-of-principle clinical trial to assess the safety and efficacy of GTCs for the chemoprevention of CaP in HG-PIN volunteers. The purity and content of GTCs preparations were assessed by high-performance liquid chromatography [(-)-epigallocathechin, 5.5%; (-)-epicatechin, 12.24%; (-)-epigallocatechin-3-gallate, 51.88%; (-)-epicatechin-3-gallate, 6.12%; total GTCs, 75.7%; caffeine, <1%]. Sixty volunteers with HG-PIN, who were made aware of the study details, agreed to sign an informed consent form and were enrolled in this double-blind, placebo-controlled study. Daily treatment consisted of three GTCs capsules, 200 mg each (total 600 mg/d). After 1 year, only one tumor was diagnosed among the 30 GTCs-treated men (incidence, approximately 3%), whereas nine cancers were found among the 30 placebo-treated men (incidence, 30%). Total prostate-specific antigen did not change significantly between the two arms, but GTCs-treated men showed values constantly lower with respect to placebo-treated ones. International Prostate Symptom Score and quality of life scores of GTCs-treated men with coexistent benign prostate hyperplasia improved, reaching statistical significance in the case of International Prostate Symptom Scores. No significant side effects or adverse effects were documented. To our knowledge, this is the first study showing that GTCs are safe and very effective for treating premalignant lesions before CaP develops. As a secondary observation, administration of GTCs also reduced lower urinary tract symptoms, suggesting that these compounds might also be of help for treating the symptoms of benign prostate hyperplasia. Cancer Res. 2006 Jan 15;66(2):1234-40. (Bettuzzi S, et al 2006)


A combination of tomato and soy products for men with recurring prostate cancer and rising prostate specific antigen.

Grainger EMSchwartz SJWang SUnlu NZBoileau TWFerketich AKMonk JPGong MCBahnson RRDeGroff VLClinton SK. Nutr Cancer. 2008;60(2):145-54.The Ohio State University, Columbus, Ohio 43210, USA.

Abstract

Tomato and soy products are hypothesized to reduce the risk of prostate cancer or enhance efficacy of therapy. A study was completed to determine if men with active prostate cancer will adhere to a dietary intervention rich in tomato products and a soy protein supplement men (n = 41) with recurrent, asymptomatic prostate cancer were randomized among 2 groups: Group A (n = 20) consumed tomato products (no soy) for Weeks 0 through 4, targeting a minimum of 25 mg of lycopene/day. Group B (n = 21) consumed soy (no tomatoes) for Weeks 0 through 4, providing 40 g of soy protein/day. For Weeks 4 through 8, all men consumed a combined tomato-rich diet and soy supplements. No grade II through IV toxicities were observed. During Weeks 0 through 4, mean daily lycopene intake for Group A was 43 mg (+/- 15 mg) and mean soy intake for Group B was 39 g (+/- 1 g), remaining similar during Weeks 4 through 8. Serum lycopene increased from 0.72 +/- 0.09 micromol/l to 1.21 +/- 0.10 micromol/l (P < 0.0001) and urinary isoflavone excretion increased from not detectable to 54.1 +/- 5.7 micromol/l (P < 0.05) with 8 wk of diet intervention. Serum prostate-specific antigen decreased between Weeks 0 and 8 for 14 / 41 men (34%). Mean serum vascular endothelial growth factor for the entire group was reduced from 87 to 51 ng/ml (P < 0.05) over 8 wk. In conclusion, prostate cancer patients will consume diets rich in tomato products and soy with excellent compliance and bioavailability of phytochemicals. Further studies combining tomato and soy foods to determine efficacy for prostate cancer prevention or management are encouraged.

Tea and lycopene protect against prostate cancer.
Prostate cancer is the most common male cancer in developed countries and is increasing in the developing world. Its long latency and geographical variation suggest the possibility of prevention or postponement of onset by dietary modification. To investigate the possible joint effect of lycopene and green tea on prostate cancer risk, a case-control study was conducted in Hangzhou, China, with 130 prostate cancer patients and 274 hospital controls. Information on tea and dietary intakes, and possible confounders was collected using a structured questionnaire. The risk of prostate cancer for the intake of tea and lycopene and their joint effect were assessed using multivariate logistic regression models. Prostate cancer risk was reduced with increased consumption of green tea. The protective effect of green tea was significant (odds ratio 0.14, 95% CI: 0.06-0.35) for the highest quartile relative to the lowest after adjusting for total vegetables and fruits intakes and other potential confounding factors. Intakes of vegetables and fruits rich in lycopene were also inversely associated with prostate cancer risk (odds ratio 0.18, 95% CI 0.08-0.39). Interaction analysis showed that the protective effect from tea and lycopene consumption was synergistic (p<0.01). This study suggests that habitual drinking tea and intakes of vegetables and fruits rich in lycopene could lead to a reduced risk of prostate cancer in Chinese men. Together they have a stronger preventive effect than either component taken separately. This is the first epidemiological study to investigate the joint effect between tea drinking and lycopene intake. Asia Pac J Clin Nutr. 2007;16 Suppl 1:453-7. (Jian LLee AHBinns CW.2007)


Whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH) and healthy male inhabitants (HMI) and prostatic tissue selenium levels (PTSL) in patients with PC and BPH.

Muecke RKlotz TGiedl JBuentzel JKundt GKisters KPrott FJMicke O. Acta Oncol. 2009;48(3):452-6.Department of Radiotherapy, St. Josefs-Hospital, Wiesbaden, Germany.

Abstract

BACKGROUND: The aim of this exploratory study was to evaluate whether significant differences exist between whole blood selenium levels (WBSL) in patients with prostate cancer (PC), benign prostatic hyperplasia (BPH), healthy male inhabitants (HMI) in northern Bavaria and the normal value. Furthermore, we investigated whether differences exist between prostatic tissue selenium levels (PTSL) in patients with PC, BPH and the benign tissue surrounding the PC.MATERIAL AND METHODS: We prospectively evaluated WBSL in 24 patients with PC, 21 patients with BPH, and 21 HMI. Measurements of PTSL were performed in 17 patients with PC and 22 patients with BPH. In 9 cases with PC, measurements were also done in the benign tissue surrounding the carcinoma. Measurements were performed using automated graphite furnace atomic absorption spectrophotometry.RESULTS: In patients with PC, there is a significantly lower WBSL in comparison to HMI (p=0.04). There is no significant difference in WBSL between BPH-patients and HMI (p=0.13) and between PC- and BPH-patients (p=0.67). In all patients and the HMI, there is a significantly lower WBSL in comparison to the recommended normal value of 85-162 microg/l (p<0.01). There is no significant difference in PTSL between PC and BPH (p=0.49), and between PC and the tissue compartment surrounding the PC (p=0.56). PTSL seemed to be reduced in the compartment surrounding the PC in comparison to BPH (p=0.03). In PC-patients, there is no significant correlation between WBSL and prostate specific antigen (PSA) (? = -0.20; p=0.36), Gleason score (? = 0.32, p=0.13), and T-stage (? = 0.22; p=0.23).CONCLUSION: Since the WBSL measured in all men with PC and BPH, and in HMI participating in our study were significantly lower than the recommended normal range, our findings may support the recommendation of selenium supplementation.


Serum and dietary vitamin E in relation to prostate cancer risk.

Weinstein SJWright MELawson KASnyder KMännistö STaylor PRVirtamo JAlbanes D. Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1253-9. Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, Department of Health and Human Services, National Cancer Institute, NIH, Bethesda, MD 20892, USA. weinstes@mail.nih.gov

Abstract

Alpha-tocopherol supplementation (50 mg daily for 5-8 years) reduced prostate cancer incidence by 32% in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study. We investigated whether serum alpha-tocopherol or intake of vitamin E (eight tocopherols and tocotrienols) was associated with prostate cancer risk with up to 19 years of follow-up in the alpha-Tocopherol, beta-Carotene Cancer Prevention Study cohort. Of the 29,133 Finnish male smokers, ages 50 to 69 years recruited into the study, 1,732 were diagnosed with incident prostate cancer between 1985 and 2004. Baseline serum alpha-tocopherol was measured by high-performance liquid chromatography and the components of vitamin E intake were estimated based on a 276-item food frequency questionnaire and food chemistry analyses. Proportional hazard models were used to determine multivariate-adjusted relative risks (RR) and 95% confidence intervals (95% CI). Higher serum alpha-tocopherol was associated with reduced risk of prostate cancer (RR, 0.80; 95% CI, 0.66-0.96 for highest versus lowest quintile; Ptrend = 0.03) and was strongly and inversely related to the risk of developing advanced disease (RR, 0.56; 95% CI, 0.36-0.85; Ptrend = 0.002). The inverse serum alpha-tocopherol-prostate cancer association was greater among those who were supplemented with either alpha-tocopherol or beta-carotene during the trial. There were no associations between prostate cancer and the individual dietary tocopherols and tocotrienols. In summary, higher prediagnostic serum concentrations of alpha-tocopherol, but not dietary vitamin E, was associated with lower risk of developing prostate cancer, particularly advanced prostate cancer.


12.  Uterine Cervical Cancer

Can Kampo therapy prolong the life of cancer patients?

Takegawa YIkushima HOzaki KFurutani SKawanaka TKudoh THarada M. J Med Invest. 2008 Feb;55(1-2):99-105. Department of Health Sciences, The University of Tokushima, Tokushima, Japan.

Abstract

Our policy regarding the performance of radiotherapy to squamous cell carcinoma of the uterine cervix has not changed since 1969. We have already reported the treatment results which were as good as those from other institutions. Since 1978, Kampo therapy was first introduced in the treatment of cancer patients in dealing with problems such as the side effects of radiotherapy and chemotherapy and various types of general malaise. We analyzed our treatment results in order to re-evaluate the chemo-radiotherapy in combination with Kampo. Survival rates for 5, 10 and 15 years, respectively, were 90.9%, 71.6% and 71.6% for Stage IB, 78.9%, 61.8% and 41.8% for Stage II, 62.3%, 49.1% and 41.2% for Stage III and 53.1%, 36.5% and 16.7% for Stage IV. The Kampo significantly extended the survival of patients with uterine cervical cancer. We intend to perform further research with more patients to explore how this therapy contributes to the prolonging of patients survival.

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Compassionate Acupuncture and Healing Arts, providing craniosacral acupuncture, herbal and nutritional medicine in Durham, North Carolina. Phone number 919-309-7753.

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One Response to Human Cancer Studies Involving Natural Compounds

  1. Cheryl says:

    Thank you for caring enough these create these webpages. There is so little mainstream information supporting the use of CAM therapies for cancer or any chronic disease.

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