COPENHAGEN, DenmarkIn the first head-to-head comparison of the two taxanes, docetaxel(Drug information on docetaxel) (Taxotere) produced significantly longer survival in patients with metastatic breast cancer, compared with paclitaxel(Drug information on paclitaxel) (Taxol), but at the cost of increased toxicity. Peter Ravdin, MD, PhD, clinical professor of medicine, The University of Texas Health Science Center, San Antonio, and principal investigator of the study, presented the phase III findings at ECCO 12, the European Cancer Conference (abstract 670). The study was sponsored by Aventis, manufacturer of Taxotere.
Between 1994 and 2001 at various centers across the United
States, Dr. Ravdin and his colleagues enrolled 449 pre- and postmenopausal
women with advanced, metastatic breast cancer who had failed treatment with
anthracycline-based chemotherapy. Half of the women were treated with
paclitaxel 175 mg/m2 in a 3-hour infusion every 3 weeks, the other
half with docetaxel 100 mg/m2 in a
1-hour infusion every 3 weeks. The treatment was continued until progression of disease, unmanageable toxicity, or intercurrent illness occurred, or until the patient decided to terminate treatment for any other reason.
The primary endpoint of the study was overall response rate. The secondary endpoints included time to disease progression and overall survival.
With docetaxel, median survival was 15.4 months, compared with 12.7 months for women receiving paclitaxel (P = .03), Dr. Ravdin reported. Median time to progression also significantly favored the docetaxel group: 5.7 months vs 3.6 months for paclitaxel (P < .0001).
The overall response rate in the intent-to-treat analysis was 32% for docetaxel vs 25% for paclitaxel (P = .10), which "approached statistical significance," Dr. Ravdin said. In the analysis of 388 eligible and evaluable patients, the overall response rate was significant in favor of the docetaxel group: 37.5% vs 26.4% (P = .02), and in this analysis, docetaxel maintained its statistical superiority in time to progression and overall survival.
Treatment with docetaxel was associated with an increased incidence of grade 3-4 toxicities, Dr. Ravdin said. Women receiving docetaxel experienced a higher incidence of grade 3-4 neutropenia (93.3% for women receiving docetaxel vs 54.5% for women receiving paclitaxel); asthenia (23.9% vs 6.8%); infections (14% vs 5%); edema (11.3% vs 4.5%); and stomatitis (10.4% vs 0.5%).
Neuromotor and neurosensory toxicities were roughly twice as high in the group receiving docetaxel, compared with the women receiving paclitaxel.
Dr. Ravdin believes that this trial has been an important study with very useful results. "Oncologists have been waiting for the outcome," he said. "It is the first time that these two drugs have been tested directly against each other. Physicians and their patients now have more definitive information about the relative effectiveness and safety of these two every-3-week chemotherapy treatments," he said.
Although all the endpoints are important, Dr. Ravdin said that overall survival is, in many ways, the most important. "In some ways, overall survival is a summation of objective response, duration of response, and tolerability," he said.
Dr. Ravdin was especially excited about the possible implications of the improvement in survival for the use of docetaxel as adjuvant therapy for breast cancer. "Usually, when a treatment shows superior survival in patients with metastatic disease, this treatment also improves survival in adjuvant therapy of early breast cancer," he said. He added that the results of recently closed and ongoing trials of docetaxel as adjuvant therapy for breast cancer are eagerly awaited.