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


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.


CONCLUSIONS
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.
P
P
Francis
E
E
Rowinsky
J
J
Schneider
T
T
Hakes
W
W
Hoskins
M
M
Markman
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017239:Paclitaxel / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010865:Pilot Projects
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel