COPENHAGEN, DenmarkIn the first head-to-head comparison
of the two taxanes, docetaxel (Taxotere) produced significantly longer survival
in patients with metastatic breast cancer, compared with 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
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%
Neuromotor and neurosensory toxicities were roughly twice as
high in the group receiving docetaxel, compared with the women receiving
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.