Approach promising for melanoma Posted Tuesday, April 16, 2002 by ctustis
Genetic technique may work for other
cancers as well By Ed Susman SPECIAL TO MSNBC

SAN FRANCISCO, April 4 — For years scientists have been trying to use a
biotechnological approach known as “antisense” to treat human cancers.
Now researchers here at a meeting of the American Association for Cancer
Research say they have been able to produce a complete response — total
disappearance of the tumor — in advanced melanoma, a difficult to treat,
fatal disease.
THE SYNTHETIC “antisense” molecule incorporates itself into a gene
responsible for key functions of the cancer cell, essentially disabling
it and preventing it from operating properly. “To our knowledge, this is
the first demonstration of clinical response using an antisense-based
therapy for solid tumors,” said Dr. Burkhard Jansen, an associate
professor of clinical pharmacology at the University of Vienna. Although
the first tests of the therapy were designed simply to establish the best
dose and establish safety, Jansen said one 90-year-old woman who was
given the antisense compound — dubbed G3139 — has been free of disease
for more than two months. In two other patients, tumors shrunk by more
than half, and in another three, tumors visibly decreased.

The average survival for the 14 patients in the study — all of whom had
exhausted standard chemotherapy efforts to control the disease — is nine
months, said Jansen. Typically, the advanced patients would be expected
to die in less than six months, he said. “This is a very exciting
development,” said Dr. Peter Jones, director of the University of
Southern California Norris Comprehensive Cancer Center in Los Angeles.
“We have all been waiting for this type of use of antisense. The study is
very encouraging.”

In the experimental therapy, researchers targeted the bcl-2 gene. In
patients with certain cancers, including melanoma, the gene produces a
chemical shield that protects tumors from chemotherapy. By not allowing
the gene to function properly, anticancer drugs were able to attack the
tumor. At a news briefing, Jansen explained that in the treatment
regimen, patients are given G3139 intravenously for five days, after
which they are administered dacarbazine (DTIC), a standard chemotherapy
agent. In advanced melanoma, DTIC is usually no longer effective against
the disease. The procedure is repeated each time DTIC is given, with some
patients receiving 10 cycles of the drug, he said. Jansen said G3139 was
well-tolerated, even by the 90-year-old. And researchers still have not
reached a maximum dose at which toxicity is great enough to halt
treatment.

Melanoma is a deadly form of skin cancer that strikes 25,800 people in
the United States a year; it is responsible for 24,000 deaths a year. The
manufacturer of G3139, Genta Inc., of Lexington, Mass., is planning to
begin a larger study of the drug with about 270 patients to be recruited
in the United States, Canada and Europe. “What is exciting about this
concept is that bcl-2 is overexpressed in a number of cancers,” Jansen
said. “Lymphoma, colon cancer, lung cancer and breast cancer could be
potential targets for this strategy.”

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