Updated International Trial Supports Cisplatin/Paclitaxel as Front-Line Treatment of Advanced Ovarian Cancer

 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.

Median Survival

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.