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

Abstract

PURPOSEThis 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 METHODSThirty-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.RESULTSMultiple 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 administratio...