Impact of antioxidant supplementation on chemotherapeutic efficacy
From the 19 studies included in a review by Block et al (2007), no evidence was found that supported concerns that antioxidant supplementation given concurrently with ROS-generating chemotherapy diminished the efficacy of the chemotherapy in study populations comprising mostly advanced or relapsed patients. In contrast, 17 of the 19 RCTs included in this review showed either a statistically significant advantage or non-significantly higher survival and/or treatment response in those patients given antioxidants. Specifically, of 13 reports on survival, all showed similar and or better and (four being statistically significant) survival rates for the antioxidant group over the control group. Additionally, while one study reported similar survival results between the antioxidant arm and control overall, the largest subgroup (stage III patients taking antioxidants) was found to have a statistically significant survival advantage compared to the control group.
For the 17 studies that reported overall response, 16 reported similar and or better and overall response rates for the antioxidant supplemented group (two being statistically significant) than the control group. Of 15 studies that reported complete response rates, all reported similar and or better response rates for the antioxidant supplemented group than the control group. One study reported complete response rates for a subgroup (surgically restaged patients taking antioxidants) that responded significantly better than the control group (46% versus 9%, P = .014).30 No studies reported significantly worse survival or response in the antioxidant supplement group.
Toxicities were also improved by antioxidant supplementation. Of 17 studies that reported general toxicities (non-neurological toxicities), 15 showed similar and or reduced and toxicities in the antioxidant group when compared with the control group. Only one study reported significantly greater general toxicity in the antioxidant group than the control, although these results were not surprising due to the well documented toxicities of high-dose vitamin A. In another study, two of eight toxicities measured were non-significantly higher, however, these results were difficult to interpret due to non-adherence within the antioxidant group. Eleven studies reported specifically on neurotoxicity and all 11 showed the antioxidant supplement group experienced similar or less neurotoxicity and than the control group.
While all of the regimens in the studies in this review included at least one drug of a class thought to produce higher levels of oxidative stress (e.g. anthracyclines, platinum coordination complexes), there is some indication that free-radical induced damage may not be the only mechanism of action of these drugs. Thus, while antioxidants may have reduced free-radical damage to normal tissues leading to diminished toxicity, the non-oxidative cytotoxic mechanisms of the drugs may remain unaffected by antioxidant supplementation. Further, the significant reductions in toxicity may alleviate dose-limiting toxicities to such an extent that more patients successfully complete prescribed regimens. Three studies reviewed reported that antioxidant groups experienced better treatment tolerance in terms of less dose-reduction and higher rates of completing full chemotherapy regimens than control groups.
Block, K.I., Koch, A.C., Mead, M.N., Peter K. Tothy, P.K., et al. Impact of antioxidant supplementation on chemotherapeutic efficacy: A systematic review of the evidence from randomised controlled trials. Cancer Treatment Reviews. Volume 33, Issue 5, August 2007, Pages 407-18. doi:10.1016/j.ctrv.2007.01.005