Painkiller Shows Promise in Prevention of Skin Cancer

Preliminary research suggests that the painkiller celecoxib (Celebrex) may help prevent nonmelanoma skin cancers, researchers reported.

In a randomized placebo-controlled trial involving more than 200 people, the drug showed no effect on the incidence of actinic keratoses, the trial’s primary endpoint, according to Craig Elmets, MD, of the University of Alabama at Birmingham, and colleagues.

But exploratory analyses of the trial data showed significant reductions in the risk of cutaneous squamous cell and basal cell carcinoma, Elmets and colleagues reported online in the Journal of the National Cancer Institute.

The researchers cautioned that the effect should be considered preliminary - since the effects on nonmelanoma skin cancers were not the primary targets of the analysis.

That said, they noted that other clinical trials have shown that celecoxib blocks sporadic colorectal adenomas and adenomas in people with familial adenomatous polyposis. “Our results extend those findings to a second target organ system,” Elmets and colleagues argued.

There is both preclinical and epidemiological data to hint that the enzyme cyclooxygenase 2 plays a role in the pathogenesis of nonmelanoma skin cancers, the researchers noted. Blocking the activity of the enzyme, then, might prevent such malignancies.

To test the idea, the researchers enrolled 240 people with between 10 and 40 actinic keratoses (skin lesions that are precursors of cancer) for nine months of therapy with either 200 mg twice daily of celecoxib or a placebo.

Elmets and colleagues counted the number of new actinic keratoses after three, six, and nine months of therapy, and then again two months after the end of therapy - but the primary endpoint was the nine-month count of new lesions.

The study was stopped early by the FDA, after another study found an increased risk of cardiovascular events associated with rofecoxib (Vioxx), another cyclooxygenase 2 inhibitor. But Elmets and colleagues found no significant difference in the risk of cardiovascular events in this study.

After nine months of therapy, they found that the incidence of new actinic keratoses did not differ between the two groups. But after adjusting for a range of factors, including Fitzpatrick skin type and cancer history, there was a significant difference in the nonmelanoma cancers:

- On average there were 0.14 nonmelanoma skin cancers among the 122 celecoxib patients, compared to 0.35 among the 118 on placebo, yielding a relative risk of 0.41, which was significant at P=0.002.
- The mean number of basal cell carcinomas was 0.07 among the celecoxib patients and 0.16 among the placebo patients, leading to a relative risk of 0.40, which was significant at P=0.032.
- The average number of squamous cell carcinomas was 0.07 in the celecoxib group and 0.19 in the placebo group, giving a relative risk of 0.42, also significant at P=0.032.
- The researchers cautioned that all of the trial participants had extensive actinic damage and it’s not clear if celecoxib would have the same effect in other populations.

Adverse events - including cardiovascular events - were not significantly different between the study arms, they added.

The surprising fact that celecoxib reduced the number of nonmelanoma skin cancers but not the number of precancerous lesions hints that carcinogenesis may differ between early- and late-stage tumor development, according to Frank Meyskens Jr., MD, and Christine McLaren, MD, of the University of California Irvine.

Writing in an accompanying editorial, they said that future trials might use a lower dose of celecoxib, given the known risk of cardiovascular events, or use a lower dose coupled with other compounds that have shown some effects in preventing skin cancers.

Primary source: Journal of the National Cancer Institute
Source reference: Elmets CA, et al “Chemoprevention of nonmelanoma skin cancer with celecoxib: A randomized, double-blind, placebo-controlled trial” J Natl Cancer Inst 2010; DOI: 10.1093/jnci/djq442.