Antioxidants

ANTIOXIDANT UPDATE

One of the most hotly debated topics in cancer currently is the question of whether antioxidants are capable of lessening the side effects & possibly improving the results of conventional cancer treatments. A recent article from the US National Cancer Institute (NCI) concluded that this is a "fertile field for future research." The NCI scientists feel, however, that "current knowledge makes it premature to generalize & make specific recommendations about antioxidant usage for those at high risk for cancer or undergoing treatment."

Premature, perhaps. Not all the possible interactions are yet fully understood. But today's patients need to make decisions today, not at some future date when consensus can finally be achieved. If you are going through chemotherapy or radiation, should you also take antioxidants? Or should you (as some oncologists advise) avoid all antioxidants, even dietary components normally found in many foods? I have heard of cancer patients who are essentially living on pretzels and water during chemo, in order to avoid "dangerous" antioxidant- rich fruits and vegetables.

Some years back the Lancet publicized the Precautionary Principle. This utilitarian rule advises scientists to make the best possible guesses in the field of public health, even when there is less than conclusive evidence. I would argue that the preponderance of evidence already suggests that antioxidants reduce the side effects of chemotherapy and radiation, without, however, interfering with their effectiveness.

Some recent findings support that position.

I have written in the past about the excellent results achieved by Dr. A. Pace & colleagues, who, by administering reasonable amounts of vitamin E to patients undergoing chemotherapy with cisplatin, succeeded in many cases in preventing the nerve damage that commonly accompanies treatment with this drug. In 7/03 another very interesting study was published on the combined use of vit. E & the drug pentoxifylline, a blood vessel dilator, in bringing about the regression of superficial radiation-induced fibrosis (RIF). (RIF is a relatively rare side effect of radiotherapy for which there is no good conventional treatment.) Like the Pace study, this was also a randomized, controlled trial, published in the orthodox Journal of Clinical Oncology. In other words, these are the kind of studies that should sway the minds of skeptical oncologists.

24 women, who together had 29 areas of RIF involving the skin & underlying tissues, were enrolled in this trial. These patients had previously received radiation for breast cancer. They were randomly assigned to one of four treatment groups: (A) pentoxifylline plus 1,000 units per day of Vitamin E; (B) pentoxifylline plus placebo (an inert pill); (C) placebo plus vitamin E; & (D) placebo-placebo. After six months, 22 patients with 27 RIF areas could be evaluated. The regression of fibrosis was significantly greater in the group using combined pentoxifylline & Vit. E than in the double placebo group. The speed of the regressions was also significantly faster in the combined treatment group.

The authors, at the Hopital Saint Louis, in Paris, France, concluded that six months' treatment of combined pentoxifylline and vitamin E "can significantly reduce superficial RIF. Synergism between PTX [pentoxifylline, ed.] & Vit. E is likely, as treatment with each drug alone is ineffective, but these results require confirmation in larger series."

True, this study concerned the use of antioxidants with a regular prescription drug given after radiation. I can't help wondering what the results would have been if the patients had been given vitamin E, with or without pentoxifylline, before and during radiation as well. Maybe RIF could actually have been prevented in the first place.

Another recent clinical study, this one published in the journal Anticancer Research, supports the use of the antioxidant hormone melatonin along with chemotherapy. Scientists randomized patients to receive the drug irinotecan (CPT-11) alone vs. irinotecan with melatonin in metastatic colorectal cancer patients whose cancer was already progressing on 5-fluorouracil-containing chemotherapy combinations."Recent advances in immunobiological knowledge," the investigators wrote, "have suggested the possibility of enhancing the therapeutic activity of various chemotherapeutic agents by a concomitant administration of anti-oxidant drugs and/or immunomodulating neurohormones" (for example, melatonin.) Melatonin is unusual in that it works both as an antioxidant and an immune modulator. This study evaluated the effect of administering melatonin alongside CPT-11, a drug widely used as second-line treatment in metastatic colorectal cancer.

Melatonin was given to such patients orally at 20 milligrams per day during the evening (when melatonin is most effective).

A partial response (PR) was achieved in 2 out of 16 patients (12.5%) treated with CPT-11 alone but in 5 out of 14 patients (35.7%) who were treated concomitantly with melatonin. Stable disease was obtained in 5 out of 16 patients (31.3%) treated with CPT-11 alone and in 7 out of 14 patients (50.0%) treated with CPT-11 plus melatonin. The degree of improvement was statistically significant. The Italian authors concluded that the effectiveness of CPT-11 may be enhanced by a daily administration of the pineal hormone and antioxidant melatonin. This accords with results that were previously reported for other chemotherapeutic agents.

If antioxidants truly interfered with radiation and chemotherapy, as some oncologists continue to maintain, then one would expect to see this interference showing up in clinical trials, such as those discussed above.

In truth, this doctrine of interference has always been based more on fear than fact. A growing body of clinical as well as laboratory data supports the concurrent use of these two important modalities. An added bonus is that antioxidants such as vitamin E and melatonin are readily available for just pennies per day. They promise a great deal of benefit for a very small price.


References

Cerea G, Vaghi M, Ardizzoia A, et al. Biomodulation of cancer chemotherapy for metastatic colorectal cancer: a randomized study of weekly low-dose irinotecan alone versusirinotecan plus the oncostatic pineal hormone melatonin in metastatic colorectal cancer patients progressing on 5-fluorouracil-containing combinations. Anticancer Res. 2003 Mar-Apr; 23(2C):1951-4.

Delanian S, Porcher R, Balla-Mekias S, Lefaix JL.Randomized, placebo-controlled trial of combined pentoxifylline and tocopherol for regression of superficial radiation-induced fibrosis. J Clin Oncol. 2003 Jul 1;21(13):2545-50.

Pace A, Savarese A, Picardo M, et al. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. J Clin Oncol. 2003 Mar 1;21(5):927-31.

Seifried HE, McDonald SS, Anderson DE, Greenwald P, Milner JA. The antioxidant conundrum in cancer. Cancer Res. 2003 Aug 1;63(15):4295-8.

See also my book, Antioxidants Against Cancer (Equinox, 2000).