A Phase III Randomized Study Comparing Paclitaxel and Cisplatin versus Cyclophosphamide and Cisplatin in Patients with Advanced Ovarian Cancer

Aim: To assess progression-free survival (PFS) and overall survival (OS) in patients with advanced epithelial ovarian cancer receiving the combination of cisplatin (75 mg/m 2 i.v.) and cyclophosphamide (700 mg/m 2 i.v.) (CP), or the combination of paclitaxel (175 mg/m 2 ) followed by cisplatin (75 mg/m 2 ) (TP). Patients and Methods: One hundred and twenty patients were randomized to receive six cycles of one of the treatments every 3 weeks. If measurable, complete response (CR) or partial response (PR) was determined. Results: There was a significant difference (p<0.05) in the frequency of response (CR+PR) rates between treatment groups, in favor of paclitaxel containing regimen. The median PFS was 9 months for patients in the CP group and 12 months for patients in the TP group (log-rank p=0.215). The median OS were 24 months and 20 months in TP and CP arms, respectively (log-rank p=0.350). Neutropenia and alopecia were more severe with paclitaxel-containing regimen. Conclusion: Although OS and PFS were similar in two arms, TP regimen yielded superior response rates relative to CP, with an acceptable toxicity profile. Therefore, the TP regimen remains the preferred initial treatment option. Surgery plays a crucial role in all phases of the management of ovarian cancer, however, is not curative due to dissemination of tumor cells throughout the abdominal cavity. Therefore, successful management generally requires additional treatment (1). The use of postoperative chemotherapy is standard for all patients with advanced- stage disease and for many patients with early-stage disease (2, 3). Cisplatin or cisplatin-based regimens have been the standard of care in women diagnosed with advanced epithelial ovarian cancer (4). Despite the established benefits of platinum-containing regimens, the prognosis for long term survival of women who are suboptimally debulked remains unsatisfactory. With paclitaxel's activity established as a salvage treatment in phase II trials of patients with ovarian cancer (5), two consecutive randomized phase III trials were carried out assessing the potential value of paclitaxel in the first-line treatment of these patients (6). The results of these trials support a survival advantage for patients treated with combinations of i.v. platinum and paclitaxel, as compared with those given a platinum plus cyclophosphamide. As reported by McGuire et al., the incorporation of paclitaxel into first-line therapy improves the duration of progression- free survival and of overall survival in women with incompletely resected stage III and stage IV ovarian cancer (7). Similarly, an analysis of the intergroup trial showed an improvement in median survival from 25 to 35 months in favor of the paclitaxel arm (8). The aim of this study was to compare the activity, in terms of progression-free and overall survival, of the combination of paclitaxel and cisplatin versus cyclophosphamide and cisplatin in patients with advanced ovarian cancer.