PHILADELPHIA – People with the heritable disorder of the
skin called Gorlin syndrome who are genetically predisposed to
develop basal cell carcinoma of the skin may have a new
chemoprevention therapy on the horizon.
According to results of a placebo-controlled, randomized,
double-blind, Phase II study, the use of celecoxib was effective in
inhibiting the development of basal cell carcinomas in a relatively
rare group of patients who are highly susceptible to carcinoma.
These findings are published in the January issue of Cancer
Prevention Research, a journal of the American Association for
Cancer Research.
Celecoxib, sold under the brand name of Celebrex by Pfizer Inc.,
is a non-steroidal anti-inflammatory drug (NSAID). Patients with
Gorlin syndrome typically develop hundreds or even thousands of
basal cell carcinomas in their lifetime.
Ervin H. Epstein Jr., M.D., senior scientist at the Children's
Hospital of Oakland Research Institute, Oakland, Calif., said the
goal of this study was to reduce the number of basal cell
carcinomas in patients with this rare disorder who are most at risk
for this form of cancer.
"The underlying idea is if we can find something in these
high-risk patients that could be translatable to the 'normal'
population, then we could ultimately use that form of
chemoprevention to reduce the numbers of skin cancer in all
people," he said.
Epstein and colleagues randomized 60 patients with basal cell
carcinoma to receive either 200 mg of oral celecoxib two times a
day or placebo. After about two years, patients who received
placebo had a 50 percent increase in basal cell carcinoma per year
compared with a 20 percent increase among those who received
celecoxib.
"We found some beneficial effect of preventing tumors in
patients treated with the NSAID," Epstein said.
Furthermore, there was no difference in the rate or severity of
side effects between patients in either group.
In a separate editorial, also published in the January issue of
Cancer Prevention Research, Charles M. Rudin, M.D., Ph.D., wrote
that "this new study of cyclooxygenase inhibition, together with
recent data on the efficacy of the hedgehog pathway inhibition,
offer new hope for patients at a high risk for basal cell
cancer."
"Basal cell carcinoma is an incredibly common disease, far and
away the most common cancer in people. The potential for a therapy
that would impact the incidence of this would be huge," said Rudin,
associate director for clinical research at the Sidney Kimmel
Comprehensive Cancer Center, Johns Hopkins.
Rudin told the American Association for Cancer Research that
while the clinical results of this study do not have an immediate
impact for patients with basal cell carcinoma, Epstein and
colleagues have set a precedent for future clinical trials.
So how do these findings translate to the clinic?
In another accompanying editorial, also published in the same
issue of Cancer Prevention Research, Jack L. Arbiser, M.D., Ph.D.,
wrote that these results demonstrate a pivotal role in the
pathogenesis of basal cell carcinoma and point towards combination
therapy among those with this form of cancer.
"This has implications for public health," said Arbiser,
professor of dermatology in the Department of Dermatology at Emory
University School of Medicine.
Although the results of this study showed positive results in
reducing cancer, Epstein suggested that concerns remain about the
potential cardiovascular side effects (i.e., stroke or heart
attack) that may be associated with this drug. More studies are
needed to validate the safety and efficacy of the use of celecoxib
in this population.
SOURCE