Phase I feasibility and pharmacologic study of weekly intraperitoneal paclitaxel: a Gynecologic Oncology Group pilot Study.

PURPOSE: This study was designed to define the maximum-tolerated dose (MTD) and pharmacology of paclitaxel administered by the intraperitoneal (IP) route on a weekly schedule. PATIENTS AND METHODS: Thirty-three patients with residual ovarian cancer following standard chemotherapy were entered onto this phase I trial. Patients were treated weekly with IP paclitaxel administered in 2 L of normal saline following premedication. Patients with nonassessable disease received 16 weekly courses. The initial dose level was 20 mg/m2/wk. There was no intrapatient dose escalation.
RESULTS: Multiple grade 2 toxicities were observed at the 75-mg/m2/wk dose level. These toxicities included abdominal pain, nausea, vomiting, leukopenia, and fatigue. One episode of grade 4 vomiting thought to be secondary to a transient partial small-bowel obstruction occurred at this dose level. At dose levels > or = 60 to 65 mg/m2, pharmacology studies documented the persistence of significant IP paclitaxel levels 1 week after drug administration, suggesting very slow peritoneal clearance and continuous exposure of the peritoneal cavity to active concentrations of paclitaxel. Low plasma paclitaxel concentrations were detected in the majority of patients treated at dose levels > or = 55 mg/m2.
CONCLUSION: Paclitaxel can be delivered by the IP route on a weekly schedule with both an acceptable toxicity profile and a major pharmacokinetic advantage for cavity exposure. The recommended dose and schedule for phase II study of IP paclitaxel is 60 to 65 mg/m2 weekly.