Antioxidants may hamper cancer therapies

Antioxidants are widely believed to help reduce the risk of certain cancers, but if taken by cancer patients undergoing cytotoxic therapy they may have a detrimental effect, according to a commentary in the Cancer Journal for Clinicians.

Antioxidants, such as vitamins A, C and E and carotenoids like beta-carotene, are believed to exert a protective effect on cells. They scavenge toxic molecules called free-radicals, which cause oxidative stress and can lead to DNA cell damage.

Gabriella D'Andrea, assistant clinical member of the Memorial Sloan-Kettering Cancer Center's department of medicine, wrote in the journal that oncologists are frequently asked what patients can do to reduce the toxicity of treatments. Surveys have shown that as many as 50 percent of cancer patients use dietary supplements.

But she warns that that there are some indications that antioxidants can actually be harmful for patients being treated with chemotherapy or radiotherapy, since they may be unable to differentiate between normal cells and cancer cells. This may mean that treatment is rendered less effective.

There is also some preclinical evidence (Vera et al; J Biol Chem 1995; 270:23706-23712) suggesting that vitamin C might have an even greater protective effect on tumors than on normal cells.

Some evidence that antioxidants may protect cells against treatment-related toxicities does exist (eg Pace et al, J Clin Oncol 2003; 21:927-931), but D'Andrea wrote that it is "promising, although not unequivocal".

As for clinical trials, despite a small number of studies seeming to indicate that antioxidants can be detrimental when patients are receiving conventional therapies, no randomized human trial has been mounted on a scale large enough to guide clinical practice.

"The harmful effects of antioxidants might be important even if they were small; a reduction of only a few percentage points in the efficacy of chemotherapy might lead to hundreds or thousands of deaths every year," she wrote.

D'Andrea holds that, until contrasting evidence from extensive human studies is available, patients should be advised against taking antioxidants during cytotoxic therapy.

D'Andrea's comments reinforce the message that patients should tell their doctor about supplements they are taking, in order to avoid potentially dangerous side effects.

In a recent survey of older Americans, 36 percent of respondents said they combine dietary supplements with prescription drugs - almost a quarter of whom did so without medical supervision.

Nor is this the first time that concerns have been raised over herbals and supplements' potential to interfere with the effects of cancer treatments. A study published in the April issue of Breast Cancer Research and Treatment found that black cohosh, a herbal with a long history of use to alleviate menopause symptoms and used by some breast cancer patients for the menopause-like side effects of cancer therapies, may interfere with some drugs.

Black cohosh was seen to increase cytotoxicity (cell killing) by two of the drugs, doxorubicin and docetaxel. It decreased the cytotoxicity of cisplatin.

No change in effect was seen in a fourth drug, 4-hydroperoxycyclophosphamide (4-HC), nor in radiation therapy.