Paclitaxel (Taxol) therapy in ovarian carcinoma

Ovarian carcinoma is the most common cause of death among the gynecologic malignancies. Primary therapy in advanced disease involves debulking surgery followed by platinum-containing chemotherapy. Despite such treatment, most patients die of residual or recurrent disease. Paclitaxel (TAXOL), a new antineoplastic agent, has response rates of 20% to 35% in phase II studies in patients with refractory ovarian cancer. Most women treated in these studies had platinum-resistant disease. Toxicity was primarily hematologic and neurologic. The findings from a large European-Canadian study suggest that hematologic toxicity is schedule dependent whereas neurologic toxicity is dose dependent. Dose escalation of paclitaxel with granulocyte colony-stimulating factor support and combinations of paclitaxel with cisplatin have been tested and shown to be feasible. Intraperitoneal administration of paclitaxel also is possible and advantageous from a pharmacokinetic perspective. In a multi-institutional randomized trial, primary treatment of patients with suboptimal disease with the combination of paclitaxel and cisplatin was compared with cyclophosphamide and cisplatin. Toxicity data from this completed trial show paclitaxel to be safe in this setting. Efficacy awaits maturity of survival data. Future clinical development of paclitaxel will include its use in less bulky disease and further evaluation of its dose escalation in advanced platinum-resistant disease. Paclitaxel currently is considered first-line treatment for platinum-resistant ovarian carcinoma. Further clinical investigation will determine its role in the primary management of ovarian cancer.