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and are less costly than randomized trials (3 , 4). Lawenda et al. further discounted 10 randomized trials that we cited because of small sample size. However, only fi ve of nine trials with concurrent radiation and fi ve of 16 trials with chemotherapy that they cited had a sample size more than 66 patients, and fi ve chemotherapeutic trials had a sample size of 20 or fewer patients. Although Lawenda et al. concluded that " high-dose antioxidant supplementation during radiotherapy decreases local tumor control and shortens the survival of cancer patients, " the very trials they cited do not substantiate these claims. Lawenda et al. also did not mention the survival benefi t demonstrated in a 100-patient study by Lissoni et al. (Table 1), thus biasing their commentary. Although most of the trials they cited demonstrated a decrease in side effects and several also showed an increase in treatment response and overall survival, one (5) reported an increase in disease recurrence and second primaries among smokers who received supplements. Although Lawenda et al. stated that " this study is the most important randomized clinical trial, to date, on the use of supplemental antioxidant and radiation therapy, " the conclusion drawn by the authors of that study was seriously fl awed because they used retrospective capsule counts by patients to assess supplement compliance and never verifi ed compliance by measuring antioxidant serum levels. Lawenda et al. further stated that " anti-cancer therapies may lower plasma antioxi-dant concentrations by altering dietary intakes. " Although this is true, we reported that plasma antioxidants are decreased mainly by chemotherapy and radiation due to lipid peroxidation. Lawenda et al. speculated that " antioxi-dants can exert their effects on all tissues to some degree, thereby protecting tumor cells as well as healthy ones. " However, the four in vitro studies they cited showed that more antioxidants accumulate in cancer cells than normal cells, which we reported (2). Accumulation of excessive antioxidants and nutrients in cancer cells can shut down oxidative reactions necessary for generating energy. Antioxidants also produce biologic effects on cancer cells unrelated to oxida-tive damage: they increase cancer cell Lawenda et al. (1) expressed concerns about our review (2) of antioxidant and nutrient use during chemotherapy or radiation. The authors stated that we reviewed 52 human trials when in fact we discussed only 50. They dismissed the 36 observational studies we reviewed on …

Re: Should Supplemental Antioxidant Administration Be Avoided During Chemotherapy and Radiation Therapy?