The role of paclitaxel in the management of coelomic epithelial carcinoma of the ovary: a review with emphasis on the Gynecologic Oncology Group experience.

Coelomic epithelial carcinoma of the ovary, the most common cause of death from cancer of the female genital tract in the United States, presents most commonly as advanced (stage III or IV) disease. Management consists of aggressive surgical cytoreduction followed by combination chemotherapy, until recently, a platinum compound plus an alkylating agent. The recent identification of the activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) offers the potential to improve further the management of patients with advanced disease. That this agent might enhance current front-line therapy is supported by its unique mechanism of action and by the significant numbers of responses reported in patients clinically resistant to the platinum compounds: more than 20% of these patients responded to paclitaxel as salvage therapy in four different phase II trials. These observations led to a phase I Gynecologic Oncology Group trial that showed that paclitaxel 135 mg/m2 over 24 hours followed by cisplatin 75 mg/m2 could be given every 3 weeks. This group then compared six cycles of the identified regimen with six cycles of standard cisplatin/cyclophosphamide chemotherapy given every 3 weeks in a phase III trial in 388 previously untreated patients with large-volume (residual nodules > 1 cm after surgery) disease. The results show the superiority of the paclitaxel/cisplatin regimen: overall response rate 77% versus 62%, clinical complete response 54% versus 33%, frequency of achieving a grossly disease-free state at second-look laparotomy 40% versus 22%, progression-free survival 18 versus 13 months, and overall survival 38 versus 24 months. Thus, paclitaxel/cisplatin is the new standard of care for patients with advanced ovarian carcinoma. Current phase III studies explore further the role of paclitaxel in front-line therapy: the relative merits of single-agent versus combination chemotherapy, the role of interval surgical cytoreduction combined with paclitaxel/cisplatin, the value of carboplatin-based versus cisplatin-based combinations with paclitaxel, the significance of the paclitaxel infusion length (3 v 24 v 96 hours), and the value of more dose-intense combinations.