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 Y. et al 2006)

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

Rebbeck TR, Troxel AB, Norman S, Bunin GR, DeMichele A, Baumgarten M, Berlin M, Schinnar R, Strom 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 TM, Lampe JW, Potter JD, Patterson RE, White 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 YJ, Yeon JY, Sung CJ, Kim HS, Sung 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 CA, Coleman EA, Stewart CB, Hakkak 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 M, Liu X, Li J, He L, Tripathy 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 J, Lee IM, Song Y, Cook NR, Selhub J, Manson JE, Buring JE, Zhang 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 R, Helzlsouer KJ, Alberg AJ, Hoffman SC, Norkus EP, Comstock 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 TD, Call TG, Zent CS, LaPlant B, Bowen DA, Roos M, Secreto CR, Ghosh AK, Kabat BF, Lee MJ, Yang CS, Jelinek DF, Erlichman C, Kay 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 KR, Brown VA, Jones DJ, Britton RG, Hemingway D, Miller AS, West KP, Booth TD, Perloff M, Crowell JA, Brenner DE, Steward WP, Gescher AJ, Brown 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 WS, Lin JK, Lin TC, Chen WS, Jiang JK, Wang HS, Chiou TJ, Liu JH, Yen CC, Chen 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 G, Watson 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 P, Airoldi M, Weber G, Drescher A, Jaehde U, Cattel 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; P_trend < 0.001) and processed meat (HR, 1.16; 95% CI, 1.01–1.32; P_trend = 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 PC, Lee MY, Wang WS, Yen CC, Chao TC, Hsiao LT, Yang MH, Chen PM, Lin KP, Chiou 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 S, Catalano V, Cordella L, Labianca R, Giordani P, Baldelli AM, Beretta GD, Ubiali E, Catalano 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 E, Sasazuki S, Inoue M, Iwasaki M, Sawada N, Takachi R, Tsugane S; Japan 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 SC, Orsini N, Wolk 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 M, Fukutomi Y, Ninomiya M, Nagura K, Kato T, Araki H, Suganuma M, Fujiki H, Moriwaki 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 E, McNeill G, Cetnarskyj R, Farrington SM, Tenesa A, Barnetson R, Porteous M, Dunlop M, Campbell 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 H, Sugiura T, Watanabe M, Norizoe C, Takahashi D, Shimojima A, Tamez S, Tsutsumi Y, Yanaga K, Urashima 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 W, Munro AJ, Guanjian 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 LY, Shan ZZ, You 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 A, Potrata B, Cheng 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 A, De Pasquale Ceratti A, Cundari S, Zanna C, Cortesi E, Crinò 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 G, Vitali G, Caraceni A, Ravaglia S, Capri G, Cundari S, Zanna C, Gianni 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 SJ, Xiao WH, Bennett 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.