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Drug may stave off skin cancer post transplant.

WAILEA, HAWAII -- Oral capecitabine shows considerable early promise for the secondary prevention of non-melanoma skin cancers in solid organ transplant recipients and other immunosuppressed individuals, according to Dr. Paul Nghiem.

Organ transplant recipients are at sharply increased risk of nonmelanoma skin cancer (NMSC). Many transplant recipients develop dozens of squamous cell carcinomas (SCCs) and/or basal cell carcinomas per year, and these tumors often behave very aggressively.

Physicians are sorely in need of additional tools to protect organ transplant recipients from NMSC--and capecitabine could fill the bill, he said at the seminar.

Capecitabine (Xeloda) is a 5-fluoro-uracil (5-FU) precursor widely used to treat colorectal cancer and metastatic breast cancer. Dr. Nghiem, a dermatologist at the University of Washington and the Fred Hutchinson Cancer Center in Seattle, credits University of Minnesota dermatologists with doing the pioneering work in developing capecitabine as a novel means of secondary prevention of NMSCs in transplant patients.

In a recent observational study, the Minnesota group reported on 15 solid organ transplant recipients, mean age 57 years, with recurrent NMSCs who were placed on low-dose capecitabine for the off-label purpose of preventing further NMSCs. The regimen was 1 g/[m.sup.2] daily on days 1-14 of a 21-day cycle.

Comparing cumulative incidence rates for NMSC during the first year on capecitabine to those the year before, the investigators found the mean number of SCCs per month declined by 0.33, the mean number of actinic keratoses fell by 2.45 per month, and the mean number of basal cell carcinomas dropped by 0.04 per month. All these reductions were statistically significant.

Toxicities were deemed manageable. Grade 3/4 toxicities consisted of fatigue in 40% of patients, hand-foot syndrome in 20%, and diarrhea in 20%. One-third of subjects discontinued capecitabine by 1 year (Clin. Transplant. 2010 Nov. 2 [doi: 10.111l/j.l399-0012.2010.01348.x]).

There are no definitive data yet, but Dr. Nghiem predicted there will not be a major rebound in NMSCs upon discontinuation of capecitabine, as occurs when systemic retinoids given for the treatment of multiple NMSCs are stopped. That's because capecitabine is actually killing cancer cells. 'After all, we don't see a rebound after we treat SCCs with topical 5-FU. I would suspect there is going to be a longer-lasting benefit than with retinoids, and that capecitabine really might be a boon to these folks," he said.

While studies of capecitabine for the secondary prevention of NMSCs continue, physicians can use several other means to protect transplant and other immunosuppressed patients. Dermatologic exams at intervals of every 3 months or less are important to detect these cutaneous tumors before they metastasize. And regular use of a broad-spectrum sunscreen has been shown to prevent the development of actinic keratoses and invasive SCCs in a randomized trial of 120 immunocompromised organ transplant recipients (Br. J. Dermatol. 2009;161:78-84).

Also, Dr. Nghiem said that calcineurin inhibitors prescribed to improve graft survival have an unwelcome effect: "They act directly on keratinocytes as a second-level fertilizer to make squamous cell carcinomas grow." Unlike calcineurin inhibitors, sirolimus does not have a direct carcinogenic effect on keratinocytes.

Dr. Nghiem said he had no relevant financial disclosures. SDEF and this news organization are owned by Elsevier.


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Title Annotation:DERMATOLOGY
Author:Jancin, Bruce
Publication:Internal Medicine News
Date:Apr 1, 2011
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