Evidence 'Equivocal' for Antioxidants in Cancer Treatment

By Michael Smith
SAN DIEGO, 28 may 2008-- The evidence for supplementing cancer radiation or chemotherapy with antioxidants is "equivocal at best" in the face of serious concerns about potential harm, researchers here said.While some studies have shown antioxidants can reduce the occurrence of clinically significant side effects, there is also evidence they can lead to lower tumor control, according to Brian Lawenda, M.D., of the Naval Medical Center San Diego, and colleagues.Until the safety issue is sorted out, oncologists and patients should be leery of the combination of radiation or chemotherapy with antioxidants, Dr. Lawenda and colleagues wrote online in a commentary in the Journal of the National Cancer Institute.
"Without strong safety data, it should be discouraged," Dr. Lawenda said, adding he and his colleagues have urged more research on the question.
The difficulty is that radiation therapy and some forms of chemotherapy -- anthracyclines and platinum-based agents, for example -- act by creating free radical damage in tumor cells. Antioxidants prevent or reduce such damage.
But the extent and effect of the possible interactions of various drugs, radiation regimens, and antioxidants has not been clearly established, they said.
Dr. Lawenda and colleagues studied published randomized clinical trials in which antioxidants were used with either form of cancer treatment.
Generally, they said, the trials were small but a few of those testing radiation therapy plus antioxidants had several hundred patients and one had 1,451.
That study, reported in 2006, was a meta-analysis of 14 randomized controlled trials that tested the antioxidant amifostine (Ethyol) in patients with various forms of cancer.
The analysis showed significant reductions (P<0.001) in a range of side effects, including a 63% reduction in the risk of developing mucositis and an 85% reduction in the risk of acute pneumonia.
At the same time, there was no difference in control rates, Dr. Lawenda and colleagues said.
On the other hand, a 2005 study randomized 540 radiation patients with head and neck cancer to get placebo or the antioxidant alpha-tocopherol, with or without the antioxidant beta-carotene.
Those who received both antioxidants had a 38% reduction in severe, acute side effects, which was significant at P<0.05, the researchers said. But the benefit was coupled with reductions of 29% and 56% in local tumor control rates for alpha-tocopherol and alpha-tocopherol plus beta-carotene, respectively.
All told, the researchers found nine studies testing radiation with and without antioxidants, and found data from a limited number of them that suggests antioxidants during radiotherapy decreases tumor control and shortens survival.
The researchers found 16 trials of antioxidants with chemotherapy, the largest of which had 250 patients. But because most of the studies were small, it was difficult to draw definitive conclusions either way, the researchers said.
The key clinical message, Dr. Lawenda said, is that doctors and their patients need to communicate about the use of antioxidants, especially because many such compounds are readily available and are widely publicized as having cancer-fighting benefits.
"We're saying to patients to be very careful about information coming out of the lay press," he said. And doctors, for their part, should be careful to ask patients about their antioxidant use and counsel them about the state of the science.
The study had no external support. Dr. Lawenda did not report any conflicts.
Primary source: Journal of the National Cancer InstituteSource reference:Lawenda BD, et al "Should supplemental antioxidant administration be avoided during chemotherapy and radiation therapy?" J Natl Cancer Inst 2008; 100: 773-783.