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 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
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,
Dr. Bizzari said.