SILVER SPRING, Md-The FDA's Oncologic Drugs Advisory Committee (ODAC) has voted 6 to 0 with one abstention to recommend that Rhône-Poulenc Rorer's Taxotere (docetaxel) be approved for the treatment of patients with anthracycline-resistant locally advanced or metastatic breast carcinoma.
The panel also recommended that, due to increased toxicity, the agent should not be used in patients who have poor liver function.
Problems of fluid retention with Taxotere in earlier studies, a principal stumbling block to approval, were reduced in current studies to an acceptable level by premedication with corticosteroids, the panel found.
Taxotere, which has already been approved for use in Australia, Canada, South Africa, Mexico, Uruguay, and Brazil, is a semisynthetic taxoid that promotes tubulin assembly in microtubules and blocks the disassembly of microtubules, thereby preventing cancer cells from dividing and leading to cancer cell death. Hepatic clearance is the main route of elimination.
At the ODAC meeting, Dr. Lewis Sheiner, of the University of California, San Francisco, said that an important problem to deal with when prescribing Taxotere is altered pharmacokinetics. He warned that it is crucial to identify patients who are potentially at risk of overdose due to slow drug elimination.
Of 15 factors tracked for their impact on Taxo-tere's pharmaco-kinetics, only three were found to be important, Dr. Sheiner said. Those were body size, protein binding, and, most important, hepatic function.
Daniel D. Von Hoff, MD, of the Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, said that of 1,070 patients who received Taxotere at 100 mg/m2 once every 3 weeks, the 42 with reduced drug clearance had more drug-induced toxicity, with 5 toxic deaths.