Michael J. Hawkins, MD, Associate Director, Washington Cancer Institute spoke on "Antioxidants and Vitamin/Drug Interactions". Dr. Hawkins began by discussing the types of CAM used as found in Oncology 15:1267-75, 2001. He also showed a table of types of cancer patients and CAM use from the same study. He then began talking about free radicals and conventional therapy concerns, mentioning that radiation therapy, cytotoxicity from alkylating agents, anthracycline mediated heart damage and chemotherapy mediated lung damage were all issues of concern. Antioxidants and chemotherapy concerns were then discussed. The possibility of decreased anti-tumor activity, interference with the mechanism of tumor killing or increased clearance by induction of metabolic pathways. But there was no data to support these ideas. There was also the possibility that there was increased toxicity or enhancement of cytotoxicity, and decreased clearance by inhibition of metabolic pathways. Again, no data. Dr. Hawkins discussed Vitamin C as ascorbic acid. Various reactions in the body require vitamin C including wound healing, catabolism of tyrosine, synthesis of epinephrine from tyrosine, and synthesis of bile acids. It is also "probably involved in steroidogenesis since adrenal gland contains high levels of ascorbic acid which are depleted following ACTH stimulation". He also mentioned that the use of high-dose Vitamin C is the most persistently controversial CAM therapy. Cameron and Campbell reported a benefit from 10 grams daily, 5 of 50 patients had objective tumor regression. (Chem Biol Interact 9:285-315, 1974) Linus Pauling (two-time Nobel Prize winner), and Cameron reported in 1976 on an expansion of the first series to 100 patients. Mean survival increased from 50 to 210 days compared to 1000 historical controls. (Proc Nat Acad Sci USA 73:3685-9,1976). A controlled trial was reported on in 1979 (NEJM 301:687-90, 1979) showing no benefit from ascorbic acid in patients with advanced cancer. Linus Pauling responded by stating that most of the patients were pretreated with chemotherapy. He and his associates stated: "with the possible exception of during intensive chemotherapy, we strongly advocate supplemental ascorbate in the management of all cancer patients from as early in the illness as possible." (NEJM 302:694-5, 1980) This was followed by a response from the authors, Moertel and Creagan, suggesting that the claims for vitamin C arose from speculation and non-randomized studies. The debate continued for years and is still a subject for discussion. The December 15, 1999 JNCI (volume 91, Number 24), headlined "Cancer Treatment and Vitamin C: The Debate Lingers". According to Dr. Hawkins, well controlled studies that demonstrate the effects of antioxidants on chemotherapeutic toxicity, anti-tumor effect and pharmacokinetics, do exist. Amifostine which is a synthetic antioxidant is active. Cell protection is thought to occur through scavenging oxygen-derived free radicals and hydrogen donation to repair damaged free radicals. A study of Amifostine in Ovarian cancer demonstrated a reduction in neutropenia and renal, neurologic or ototoxcity. However, there did not seem to be any effect on survival. (J Clin Oncol 14:2101-2112, 1996) Amifostine has been looked at in Head and Neck cancers (J Clin Onc 18:3339-45, 2000) and Rectal cancer (Cancer 69:2820-25, 1992). Another synthetic antioxidant appears to have been well-studied. Dexrazoxane (ICRF-187). Dr. Hawkins spoke about Glutathione as a "very potent antioxidant". Glutathione was looked at in Gastric and Ovarian cancer. In a study (Ann Oncol 8:569-73, 1997) a second look surgery found 6/13 women with a pathological complete response after receiving Cisplatin and Glutathione compared to 1/11 with Cisplatin alone. He then discussed Vitamin A which consists of three biologically active molecules: retinol, retinal (retinaldehye) and retinoic acid. It is derived from the beta-caroten. When ingested, beta-carotene converts to retinal which is reduced to retinol in the intestine. In a study on breast cancer patients, both post and pre-menopausal, (Ann Med Interne (Paris)136(7):551-4, 1985), significant response was shown in the post-menopausal group. This translated to longer survival. The doses were between 350,000 and 500,000 IU qd along with chemotherapy. Vitamin A has been studied in Head/Neck cancers, primarily in Japan. A synergy has been shown between Vitamin A and 5-FU. (Gan To Kagaku Ryoho 13(4 Pt 2):1731-6, 1986) and (Auris Nasus Larynx 12 Suppl 2:S239-43, 1985) Vitamin E has its major function as an antioxidant which scavenges free radicals and molecular oxygen. It prevents peroxidation of polyunsaturated membrane fatty acids and interacts with ascorbic acid (active alpha tocopherol is regenerated by ascorbic acid following scavenge of a peroxyl free radical). There has been much research done with heart disease and Vitamin E. It was looked at with Doxorubicin toxicity (Ann NY Acad Sci393:411-418, 1982) (J Clin Res Clin Oncol 106:143-7, 1983) Finally Co Q10 (Ubiquinone) was discussed as a powerful antioxidant. Administration of CoQ10 reverses muscle changes in patients with CoQ10 deficiency. It has been studied in patients with congestive heart failure (Chest 120:2035-3036, 2001) and for anti-tumor activity (Biochemical & Biophysical Research Communications. 1994;199:1504-8, Biochemical & Biophysical Research Communications. 1995;212:172-7 and Molecular Aspects of Medicine. 1994;15:S231-40) 32 women with breast cancer were treated with standard therapy plus nutritional antioxidants, essential fatty acids and CoQ10 90 mg qd. Survival was longer than expected. Three patients had dosage above 300 or 390 mg qd and were felt to have good anti-tumor response. Interpretation was difficult due to concurrent therapy, diagnosis of intraductal carcinoma. Overall, Dr. Hawkins pointed out that "remarkably little" is known on the subject of antioxidants. Large scale randomized trials are required to detect decreased toxicity while maintaining anti-tumor activity. This could be ethically and efficiently done in patients with advanced disease. It would provide rapid generation of information. Smaller studies could be used to address effects of antioxidants. Ann's NOTE: In our section Relevant Studies, Vitamins and Dietary Supplements, we show many studies on the topic of antioxidants. There have several reviews of existing studies. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.