Bases pharmacologiques de la chimiothérapie intrapéritonéale

Abstract

Intraperitoneal chemotherapy is a very attractive therapeutic alternative in the treatment of advanced ovarian carcinoma, due to its intraperitoneal spreading. Pharmacokinetic rational was described 30 years ago: a drug administered within the peritoneal cavity diffuse through the peritoneum towards the plasmatic compartment, depending on both its molecular weight and its lipid solubility. A slow output of the drug from the peritoneal cavity and a high plasma clearance are associated with a great pharmacokinetic advantage, illustrated by the area under the concentration time curve ratio. Then it is possible to increase the amount of drug directly delivered at the tumor site, while controlling the systemic toxicity. The agent administered in a large fluid volume come into direct contact with the tumor nodules, into which it penetrates from the free surface while it also reaches them by blood flow. The peripheral penetration being however limited to the first cellular layers, this way of delivery is interesting only for small residual disease. The most active drugs in the treatment of ovarian cancer, paclitaxel and platinum agents, are particularly convenient for this way of administration. The most optimal administration modality still remains to be defined and the development of the targeted therapies still opens new perspectives.