Introduction Dietary and endogenous antioxidants prevent cellular damage by reacting with and eliminating oxidizing free radicals. However, in cancer treatment, a mode of action of certain chemotherapeutic agents involves the generation of free radicals to cause cellular damage and necrosis of malignant cells. So a concern has logically developed as to whether exogenous antioxidant compounds taken concurrently during chemotherapy could reduce the beneficial effect of chemotherapy on malignant cells. The importance of this concern is underlined by a recent study which estimates 23 percent of cancer patients take antioxidants.1 The study of antioxidant use in cancer treatment is a rapidly evolving area. Antioxidants have been extensively studied for their ability to prevent cancer in humans.2 This paper reviews the use of antioxidants as a therapeutic intervention in cancer patients, and their potential interactions with radiation and chemotherapy. There has been significant investigation of this area, with promising findings which indicate continuing investigation is warranted. For further discussion of the use of antioxidants as sole cancer therapy, refer to the review article by Prasad published earlier this year.3 A number of reports show a reduction in adverse effects of chemotherapy when given concurrently with antioxidants. These data are more completely summarized by Weijl et al.4 Conflicting Views of Antioxidant Use in Cancer Therapy It was suggested in a recent publication that no supplementary antioxidants be given concurrently with chemotherapy agents which employ a free radical mechanism.5 The paper must be commended for pointing out that the combination of antioxidants and chemotherapy agents needs more investigation, and should serve as a wake-up call regarding how much we need further definition of the actions of specific antioxidants with chemotherapeutic agents. However, it should not serve as scientific closure on an adjunctive treatment of possible great promise in cancer therapy. The present authors are by no means recommending any lack of caution about use of antioxidants. On the contrary, published research indicates the cautious and judicious use of a number of antioxidants can be helpful in the treatment of cancer; as sole agents and as adjuncts to standard radiation and chemotherapy protocols. It was suggested that antioxidants might interfere with the oxidative mechanisms of alkylating agents.5 These drugs create substantial DNA damage, resulting in cell necrosis. However, recent evidence indicates a sizeable amount of chemotherapy damage is by other mechanisms, which trigger apoptosis.6 Antioxidants have been shown to increase cell death by this mechanism.7,8 Given this, any argument that antioxidants are likely to interfere with most chemotherapy is too simplistic and probably untrue. Numerous animal studies have been published demonstrating decreased tumor size and/or increased longevity with the combination of chemotherapy and antioxidants.7,9-16 A recent study was conducted on small-cell lung cancer in humans using combination chemotherapy of cyclophosphamide, Adriamycin (doxorubicin), and vincristine with radiation and a combination of antioxidants, vitamins, trace elements, and fatty acids. The conclusion was "antioxidant treatment, in combination with chemotherapy and irradiation, prolonged the survival time of patients" compared to expected outcome without the composite oral therapy.17 Two human studies found melatonin plus chemotherapy to induce greater tumor response than chemotherapy alone.18,19 The treatments producing these positive results would have been advised against by those advocating no antioxidant use during chemotherapy. These studies will be discussed in more detail below. It is the opinion of the authors of this paper that interactions between antioxidants and chemotherapeutics cannot be predicted solely on the basis of presumed mechanism of action. The fact remains that physicians must be aware of the available research to help their patients take advantage of positive interactions existing between antioxidants and chemotherapy or radiation. Additionally, physicians need to remain aware of the large body of evidence showing a positive effect of antioxidants in the period following chemotherapy administration. The general protocol with standard oncologic therapies is to follow a watch-and-wait strategy after therapeutic administration is concluded. This is a period when supplemental therapies are highly indicated and have been demonstrated to result in a higher percentage of successful outcomes.20,21 Alternative Medicine Reviews, 1999;4(5):304-329 With chemotherapy & with radiation therapy References Vitamin A With chemotherapy & with radiation therapy References Vitamin C Discusses both chemotherapy and radiation therapy Alternative Medicine Reviews, 1999;4(5):304-329 References Overview of Chemotherapeutic Agents With chemotherapy & with radiation References Vitamin E With chemotherapy & radiation References on Melatonin With chemotherapy & with radiation References on Selenium With chemotherapy & with radiation References CoQ10 With chemotherapy & radiation References NAC and Glutathione With chemotherapy & radiation References on Flavinoids This MUST be explored further Alternative Medicine Reviews, 1999;4(5):304-329 References Combining Antioxidants Some caveats to antioxidant use References Current Attitudes Smiling Dog Foundation & Bastyr University supported this work Alternative Medicine Reviews, 1999;4(5):304-329 References for Conclusions Antioxidants in Chemotherapy Remember we are NOT Doctors and have NO medical training. 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