Fluorouracil May Boost Invasive Skin Cancer Risk in Some

November 26, 2013

By David Douglas

NEW YORK (Reuters Health) Nov 26 - Topical fluorouracil may increase the risk of morpheaform basal cell carcinoma (mBCC) in patients with previous skin cancers, according to data from a VA study.

The VA Topical Tretinoin Chemoprevention (VATTC) trial "included a careful evaluation of a cohort at high risk for keratinocyte carcinomas," Dr. Martin A. Weinstock told Reuters Health by email.

"In it, we noted that prior use of topical 5-FU (5-fluorouracil) increased risk of morpheaform basal cell carcinoma, a relatively difficult to clear and invasive form of skin cancer."

According to a research letter online November 20th in JAMA Dermatology, Dr. Weinstock of the VA Medical Center in Providence, Rhode Island and colleagues studied data on 1131 patients, each with at least two prior keratinocyte carcinomas.

After a mean follow-up of 3.6 years, mBCC developed in 50 participants. This amounted to 10% of those in whom any BCC developed.

The most important risk factor was the number of BCCs in the five years before enrollment (hazard rate ratio, 7.06). Other significant predictors included a history of ever using fluorouracil, sun sensitivity, and the number of actinic keratoses at baseline.

Further analysis, with the study site excluded, showed that the number of prior BCCs and use of fluorouracil were the only two predictors of mBCC.

Fluorouracil use was also significantly more likely to cause mBCC than non-morpheaform BCC (odds ratio, 2.48).

One possible explanation for the latter finding, say the investigators, is that "Fluorouracil treatment may eliminate some superficial BCCs but leave mBCCs intact."

Fluorouracil, they add, "may also have destroyed cancer cells at the surface while deeper pockets remained viable and later proliferated, resulting in mBCCs."

"The possibility that fluorouracil treatment may predispose to development of mBCC warrants further investigation," they conclude.

Dr. Weinstock stressed that in patients with previous fluorouracil use "dermatologists should be aware of the risk of mBCC," but no special monitoring is required. The study patients, he pointed out, were high risk and "these findings may or may not apply to lower risk populations."

Commenting on the findings by email, Dr. Steven M. Daines said the study "reminds us that in managing complex disease processes like skin cancer, our treatments can have unintended consequences."

Dr. Daines of Daines Plastic Surgery in Newport Beach, California added, "Although fluorouracil is effective at eliminating superficial skin cancers, it may leave behind deeper tumor cells that can evolve into more aggressive carcinomas. The skin oncologist should be aware of this phenomenon and maintain an appropriate index of suspicion during treatment follow-up."

SOURCE: http://bit.ly/1icCdsc

JAMA Dermatol 2013.

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