Docetaxel (Taxotere) was recently approved by
the Food and and Drug Administration (FDA) for the treatment of
locally advanced or metastatic nonsmall-cell lung cancer
(NSCLC) after failure of prior platinum-based chemotherapy.
Taxotere is the first chemotherapeutic agent to be approved by
the FDA for the second-line treatment of advanced nonsmall-cell
lung cancer, said John Leone, senior vice president, US
Commercial Operations, Aventis Pharmaceuticals (the company created
by the recent merger between Hoechst Marion Roussel, Inc., and
Rhone-Poulenc Rorer Pharmaceuticals, Inc.). We hope this new
approval for Taxotere will enable physicians to extend the lives of
nonsmall-cell lung cancer patients who previously had limited
options once their disease had progressed.
The approval of this new indication for docetaxel was based on the
results of two randomized, phase III clinical trials conducted in
patients with advanced NSCLC.
We found that patients treated with Taxotere in the second-line
setting had a significant improvement in their survival, said
Frank V. Fossella, MD, medical director, Thoracic Medical Oncology
Multidisciplinary Care Center at The University of Texas, M. D.
Anderson Cancer Center in Houston, and primary investigator of one of
the trials. Standard treatment regimens for this patient
population have shown no evidence of survival improvement. With the
1-year survival rates seen in both trials, Taxotere should be
considered the standard of care for these patients with advanced
nonsmall-cell lung cancer.
Docetaxel vs Best Supportive Care
In a worldwide, multicenter, phase III trial, 204 patients who had
not responded to previous platinum-based chemotherapy received either
75 or 100 mg/m² of docetaxel every 3 weeks plus best supportive
care or best supportive care alone. Patients treated with docetaxel
had a median survival of 7.5 months vs 4.6 months in patients who
received best supportive care alone. The times to disease progression
were 12.3 and 7 weeks in the docetaxel and best supportive care
groups, respectively. The 1-year survival rate was significantly
higher in group treated with docetaxel than in the group who received
best supportive care alone (37% vs 12%).
A clinical-benefit analysis showed that patients treated with
docetaxel did not experience a deterioration in performance status or
Docetaxel vs Vinorelbine or Ifosfamide
In the other phase III study, 373 patients with advanced NSCLC whose
disease was resistant to platinum-based chemotherapy received
treatment with docetaxel, 75 or 100 mg/m² every 3 weeks,
vinorelbine (Navelbine), 30 mg/m² weekly, or ifosfamide (Ifex),
2 g/m² daily for 3 days every 3 weeks. The study, conducted at
23 cancer centers in the United States, found that patients treated
with 75 mg/m² of docetaxel had a 1-year survival rate of 30%, as
compared with a rate of 20% in patients treated with either
vinorelbine or ifosfamide.
The major side effects of docetaxel in observed in both phase III
trials were myelosuppression, fatigue, nausea, and alopecia.
In patients with normal liver function, side effects of docetaxel
that have been reported include neutropenia, thrombocytopenia,
anemia, fluid retention, hypersensitivity, nausea, and diarrhea. A
premedication regimen with corticosteroids is recommended to prevent
or reduce hypersensitivity and fluid retention. Docetaxel is
generally not appropriate therapy for patients with liver impairment.