Intraperitoneal paclitaxel: pharmacology, clinical results and future prospects.

Abstract

Paclitaxel administered into the peritoneal cavity is a chemotherapy agent that shows unusually prolonged retention within the peritoneal space. Using this pharmacokinetic fact as a starting point, the use of this drug to benefit patients with peritoneal metastases was investigated. The pharmacokinetics and drug characteristics of paclitaxel were identified from the oncologic literature. The experience to date with ovarian cancer, malignant peritoneal mesothelioma, gastric cancer and pancreas cancer was explored. Paclitaxel given by repeated instillation through an intraperitoneal port has demonstrable responses in ovarian cancer, peritoneal mesothelioma, gastric cancer and pancreas cancer when peritoneal metastases are present. Its role for prevention of peritoneal metastases in patients at high risk seems less well established. Randomized controlled studies have been positive in ovarian cancer but not in other diseases with peritoneal dissemination. A randomized controlled study in gastric cancer with peritoneal metastases produced suggestive but not conclusive results. Conversion surgery after repeated treatments with intraperitoneal paclitaxel has been reported with gastric cancer and pancreas cancer with peritoneal metastases. The pharmacology of intraperitoneal paclitaxel strongly suggest that intraperitoneal administration should be of benefit to prevent or treat peritoneal metastases. Protocols that the oncologist can follow to realize these potential benefits are not as yet available.