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Oncology NEWS International. Vol. 4 No. 7
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ODAC Recommends Accelerated FDA Approval of Ethyol for Cytoprotection

July 1, 1995

ROCKVILLE, Md--The Food and Drug Administration's Oncologic Drugs Advisory Committee (ODAC) has voted unanimously to recommend accelerated approval of Ethyol (amifostine injection) as a cytoprotective agent against cumulative renal toxicities associated with cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar) and cisplatin(Drug information on cisplatin) (Pla-tinol) in patients with advanced solid tumors of non-germ-cell origin.

Accelerated approval, as opposed to unconditional approval, means that a new drug may be marketed, but FDA will require additional studies to determine if the observed effect will lead to clinically meaningful benefits. If such studies are inconclusive, or if the company, in this case, U.S. Bioscience, does not perform them, FDA reserves the right to withdraw the accelerated approval.

Efficacy and Safety

In a randomized, double-blind study, women with ovarian cancer were divided into two arms: one group received cis-platin and cyclophosphamide alone and the other group received the two chemotherapeutic agents with Ethyol. The objective was to determine whether amifostine(Drug information on amifostine) reduced cumulative renal toxicity associated with cisplatin, as measured by creatinine clearance levels.

The toxic effects of cisplatin therapy (neurotoxicity, ototoxicity, myelosuppression, and neutropenia, as well as nephrotoxicity) can be permanent and severe. Patients may be left with significant reduction in renal function, which can preclude their ability to receive further cisplatin therapy, thus shortening their lives.

Moreover, renal failure, myelosuppression, and neutropenia can negatively affect the action of other chemotherapeutic agents such as carboplatin(Drug information on carboplatin) (Paraplatin), methotrexate(Drug information on methotrexate), and bleomycin(Drug information on bleomycin).

According to U.S. Bioscience, Ethyol, when given with cisplatin, reduced nephrotoxicity, ototoxicity, and peripheral neuropathy. In addition, possible confounding factors, such as preexisting diabetes, preexisting hypertension, and the existence of other tumors, had no significant negative effect on the efficacy of amifostine.

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