ROCKVILLE, Md--The FDA's Oncologic Drugs Advisory Committee has
declined to recommend Ethyol (amifostine injection, U.S. Bioscience,
Inc.) for approval at this time. The drug is being considered
as a cytoprotective agent against both the acute and cumulative
hematologic and renal toxicities associated with alkylating agents
such as cyclophosphamide (Cytoxan, Neo-sar) and platinum agents
such as cisplatin (Platinol) in patients with ovarian cancer.
Although there was general agreement among the committee members
that amifostine does indeed have a biologic effect, they found
that the data submitted did not make clear whether that effect
is sufficient for approval.
Robert L. Capizzi, MD, U.S. Bioscience executive president, said
that the company has since had a constructive meeting with the
FDA, resulting in an FDA proposal that the company submit an amendment
to its NDA for Ethyol based on analyses of the existing clinical
data. The company intends to submit this amendment and anticipates
returning to the committee by mid-year 1995.
He added that the recent recommendation for approval of the drug
in Europe and the anticipated commercial sale in the United Kingdom
should provide opportunities to demonstrate Ethyol's clinical
benefit for cancer patients.
A U.S. Bioscience representative said that the treatment for ovarian
cancer patients has improved somewhat over the past several years
but at a great cost in toxicity.
In its presentation of Ethyol trials in patients with advanced
ovarian cancer and melanoma being treated with alkylating and
platinum agents, the company claimed that pretreatment with Ethyol
led to a significant decrease in hematologic, renal, neurologic,
and otologic drug toxicity, without reducing the antitumor effects
U.S. Bioscience representatives also said that use of Ethyol decreased
the incidence of infections associated with neutropenic fevers,
resulting in fewer days of hospitalization and fewer days on antibiotics
in the ovarian cancer trials.