ROCKVILLE, Md--In a surprise move, the FDA Oncologic Drugs Advisory Committee failed to recommend approval of Taxotere (docetaxel, Rhône-Poulenc Rorer) for commercial use.
The drug was being considered for approval in patients with locally advanced or metastatic breast carcinoma in whom previous therapy with an anthracycline has failed, and patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) after failure of platinum-based therapy.
The panel characterized docetaxel(Drug information on docetaxel) as very efficacious, but noted the drug's significant toxicity. In addition, the panel felt that it was difficult to judge the net benefit of docetaxel based only on phase II trials and urged the company to begin phase III trials, including randomized trials of untreated lung cancer that would test docetaxel against approved drugs.
Taxotere, which is derived from the needles of yew trees instead of the tree bark, thus forestalling destruction of the trees, has a 40% to 70% response rate in clinical trials of previously untreated metastatic breast cancer patients, the company said in its presentation.
According to Jean-Pierre Bizzari, MD, of Rhône-Poulenc Rorer, of the 912 patients in phase I/II trials, 10% to 15% of untreated breast cancer patients had an unequivocal complete remission (mean duration, 10 months). The optimum dose was 100 mg/m² per treatment cycle.
The major side effect was neutropenia. Other adverse effects included leukopenia; anemia (rare); alopecia, which was almost universal; skin toxicity, which can be successfully controlled with corticosteroids; and fluid retention, which was the principal reason for discontinuation.
The cumulative effects of fluid retention can be managed by corticosteroids and can be prevented to some extent by premedication with dexamethasone(Drug information on dexamethasone), Dr. Bizzari said.