Phase I trial of intraperitoneal taxol: A gynecoloic oncology group study

Purpose: To evaluate the safety and pharmacology of the intraperifoneal (IP) administration of the antineoplastic agent taxol. Patients and Methods: Twenty-five pretreated patients who were entered onto a phase I clinical trial; 24 had advanced ovarian cancer. Patients were treated with taxol administered IP in 2 L of normal saline every 3 to 4 weeks. The starting dose was 25 mg/m². There were no intrapatient dose escalations. Results: The dose-limiting toxicity was the development of severe abdominal pain at taxol doses more than 175 mg/m². Moderate leukopenia (WBC count < 2,0007 mm³) was observed at IP doses of ≥ 175 mg/m². The exposure of the peritoneal cavity (peak levels and area under the time-versus-concentration curve [AUC]) to taxol after IP delivery exceeded that of the plasma by approximately 1,000-fold. However, concentrations of the agent previously shown to produce cytotoxicity in experimental systems were demonstrated in the systemic compartment after regional delivery, which was considered important. Significant concentrations of taxol persisted within the peritoneal cavity for more than 24 to 48 hours after a single IP installation. Several antitumor responses, which included control of platinum-refractory ascites, were documented. Conclusion: Taxol can be delivered by the IP route with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure.