LOS ANGELES--The use of cisplatin (Platinol)/paclitaxel (Taxol)
for first-line treatment of advanced ovarian cancer gained additional
support from the final survival analysis of a major international
study presented at an ASCO scientific session.
Gavin C. E. Stuart, MD, of the University of Calgary, reported that
after a median 30 months of follow-up, women treated with
cis-platin/paclitaxel had significantly better overall survival and
progression-free survival than those treated with standard cyclophosphamide/cisplatin.
This survival benefit occurred even though patients whose disease
progressed on the cyclophosphamide/cisplatin arm could cross over to
a taxane-containing regimen. Women randomized to the
cisplatin/paclitaxel treatment arm had a reduction of about 30% in
risk of death (risk ratio adjusted for all prognostic factors, 0.71).
Dr. Stuart reported these results on behalf of the European-Canadian
Intergroup study, conducted by the EORTC, the NOCOVA, the NCI-Canada
Clinical Trials Group, and the Scottish Group.
This updated analysis confirmed preliminary results reported at ASCO
in 1997 and also confirmed results of the Gynecologic Oncology Group
study GOG-111, the first large randomized trial comparing the two combinations.
The European phase III trial included 680 patients with advanced
epithelial ovarian cancer (FIGO stages IIB, IIC, III, and IV). Women
with either suboptimally or optimally debulked ovarian cancer were eligible.
Patients were randomized to cyclophosphamide (750 mg/m²)
followed by cisplatin (75 mg/m²) every 3 weeks, or to paclitaxel
(175 mg/m² as a 3-hour infusion) followed by cisplatin every 3
weeks. Paclitaxel could be escalated to 200 mg/m² in the second
cycle in those patients who did not experience febrile neutropenia.
Patients were assessed after 3 cycles, and those with progressive
disease were removed from the protocol. All other patients were
scheduled to receive between 3 and 6 more cycles of chemotherapy.
Dr. Stuart also pointed out that patients could undergo interval
debulking surgery after completion of the first 3 cycles of treatment
if they were suboptimally debulked at the time of randomization.
"This strategy had previously been demonstrated to be effective
in a published EORTC trial," he said.
Progression-free survival rather than overall survival was the
primary endpoint. "This was done because of the wide
availability of paclitaxel at the time of the conduct of the study
and the anticipated high crossover rate for second-line
treatment," Dr. Stuart said. Of the 330 women randomized to
cyclophosphamide/cisplatin, 253 progressed on treatment, and 134
(52%) of these received a taxane.
Dr. Stuart reported that 668 patients were eligible for analysis at a
median follow-up of 30 months. "Median survival for patients on
the paclitaxel/cisplatin arm is 35 months vs about 25 months for
those on cyclophosphamide/cis-platin," he said. This was highly
significant at P < 0.001.
This survival advantage was apparent for both optimally debulked and
suboptimally debulked disease, he said, although the numbers were too
small to reach significance.
Progression-free survival, as reported last year, was 16 months in
the cisplatin/paclitaxel arm vs 12 months in the control arm, and the
advantage for cisplatin/paclitaxel was also demonstrated for both
optimally and suboptimally debulked disease.
Quality of life data are available for 210 patients. Ultimately, Dr.
Stuart said, there were no significant differences in effects on
global quality of life, cognitive functioning, insomnia, pain,
appetite loss, constipation, or fatigue, although there were
transient differences at various points over the 30-month period.