| May 31, 2003
Early Study Results Promising: Oral
Medication Active Against Skin Cancer
Abramson Cancer Center Research Presented at ASCO:
IL) - Researchers from the Abramson Cancer Center of
the University of Pennsylvania today presented early
study results showing that a new kind of drug, a Raf
kinase inhibitor, is well tolerated and may prove effective
in treating patients with metastatic melanoma, the most
severe form of skin cancer. Standard chemotherapy has
limited effectiveness against metastatic melanoma (i.e.
The findings were released by co-Principal
Investigators Keith Flaherty, MD, and Peter O'Dwyer,
MD, at the 39th Annual Meeting of the American Society
for Clinical Oncology, taking place in Chicago, May
31 to June 3. Early results from a Phase I clinical
study show that the Raf kinase inhibitor produced promising
anti-cancer activity in patients with metastatic (or
widespread) melanoma: Seven out of ten patients tested
showed benefit that lasted up to ten months. The investigational
drug, named BAY43-9006, is a pill therapy under development
by Bayer and Onyx Pharmaceuticals.
"It is promising to see patients do so
well, this early in the research," said Flaherty, Instructor
of Medicine at the Abramson Cancer Center of the University
of Pennsylvania. "Melanoma is a disease that does not
frequently respond to current therapies."
Raf kinase inhibitors are small molecules
that prevent or interrupt the action of Raf kinase,
a key enzyme in the chain reaction of the body's chemistry
that triggers cell growth. Abnormal activation of this
pathway is a common thread in the development of most
cancers, including two-thirds of melanomas. By blocking
the action of Raf kinase, scientists hope they can reverse
the progression of these tumors.
Twenty patients were enrolled in the first
part of the Phase I study, which began in April 2002.
The Phase I trial was funded through a research grant
from Bayer Pharmaceuticals.
The primary goal of the Phase I trial
is to determine a safe dosage of the Raf kinase inhibitor
for use in future studies. Patients were given the Raf
kinase inhibitor, twice daily - in varying doses of
either 100 mg, 200 mg, or 400 mg - for a period of three
weeks, in combination with two standard cancer therapies,
carboplatin and paclitaxel.
The safety profile of the combination
therapy was determined as favorable, with minimal and
reversible side effects, such as rash and diarrhea.
"With this study, we have confirmed that
the Raf kinase inhibitor can be used safely in conjunction
with other standard cancer therapies," said O'Dwyer,
Director of the Developmental Therapeutics Program and
Professor of Medicine at the Abramson Cancer Center
of the University of Pennsylvania. "Associated laboratory
studies show that the Raf kinase inhibitor, at these
doses, blocks the target pathway. Our next step is to
continue to investigate this further in order to develop
effective therapies for this life-threatening disease."
For 2003, the American Cancer Society
estimates that over 54,000 Americans (2,700 Pennsylvanians)
will be diagnosed with melanoma and 7,600 will die from
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Editor's Note: Neither Drs.Flaherty
or O'Dwyer have any financial interest in Bayer or Onyx