New Drug Effective for Rare Genetic Skin Cancer: Studies

WEDNESDAY, June 6 (HealthDay News) — When a clinical trial is
stopped abruptly just eight months after its start, it’s either very good
or very bad news.

In the case of a study on a skin cancer drug, the results were so
impressive that the trial’s independent data and safety monitoring board
decided to offer the drug immediately to the study participants who were
taking placebos.

The drug, vismodegib (Erivedge), was approved in January by the U.S.
Food and Drug Administration for people with aggressive, large basal cell
carcinoma that had spread to the lymph nodes or other body systems. The
researchers wanted to test the oral medication against a disfiguring form
of skin cancer called basal cell nevus syndrome, a rare genetic
condition.

Researchers followed 41 patients with basal cell nevus syndrome and
found that those taking vismodegib got an average of slightly more than
two new cancers, while those not taking the drug developed 29.

The study was reported in the June 7 New England Journal of
Medicine
.

“This is one of the first clinical trials that show the drug can be
used in prevention,” said Dr. Jean Tang, a co-author of the study and
assistant professor in the department of dermatology at Stanford
University School of Medicine.

Tang said the positive effects of the drug are visible within a month
after starting to take it. “This is a life-changing drug for these
patients,” she said.

Basal cell nevus syndrome typically starts at puberty. The condition
can involve hundreds of basal cell lesions, often requiring many surgical
and nonsurgical procedures to treat.

Basal cell carcinoma of the skin is the most common cancer worldwide,
and its prevalence is increasing. There are about 2.1 million new cases of
non-melanoma skin cancer treated in the United States every year,
according to journal background information. Some 750,000 of these are
cases of basal cell carcinoma. Basal cell nevus syndrome — also known as
Gorlin syndrome– occurs in fewer than 1 percent of them.

The study tracked more than 2,000 existing basal cell skin cancers and
documented 694 new lesions in the study group.

The research also provides new evidence about a key genetic pathway in
the development of basal cell and other cancers. Vismodegib targets what
is called the “hedgehog-signaling pathway.” (It was named after mutant
mouse embryos in early studies that looked like hedgehogs.)

The pathway directs cell growth in embryos and also regulates adult
stem cells involved in maintaining and regenerating tissue. If the pathway
malfunctions, it can result in basal cell carcinoma and other cancers.

“The research trial demonstrates proof of the impact of the
hedgehog-signaling pathway in basal cell cancers,” Tang said. The findings
may have broader relevance to treating other types of basal cell skin
cancer, she said.

The drug’s side effects, including muscle cramps, changes in taste
perception, weight loss, hair loss and fatigue, can be debilitating. In
order to reduce their impact, the researchers are testing whether dosing
the drug intermittently — two months on, two months off — will reduce
the symptoms while still being at least 90 percent effective. They’re also
testing reduced dosages to better understand how to strike the right
balance, Tang said.

At this point, vismodegib costs $250 a day, Tang said. The drug’s
maker, Genentech, contributed nearly $1 million to support the research,
including the costs of patient travel, office visits and biopsies, she
said.

A second, related study in the same journal issue found that some
patients responded to vismodegib for locally advanced and metastatic basal
cell carcinomas. This study also received funding from Genentech.

Dr. John Lear, a consultant dermatologist at the Manchester Royal
Infirmary in England, wrote an editorial on the studies. “It is a
landmark day for patients with basal cell carcinoma,” he said in an
interview. “The next step is to develop topical applications and
injections that could minimize side effects while effectively preventing
and treating lesions.”

More information

To learn more about basal cell nevus syndrome, visit the U.S. National
Library of Medicine.

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