Using Pharmacologic Data to Plan Clinical Treatments for Patients with Peritoneal Surface Malignancy

Kurt   Van der   Speeten; Oswald   Anthony   Stuart; Paul   H.   Sugarbaker

Abstract

The surfaces of the abdomen and pelvis are an important anatomic site for the dissemination of gastrointestinal and gynecologic malignancy. This transcoelomic spread of cancer cells gives rise to peritoneal carcinomatosis which, without special treatments, is a fatal manifestation of these diseases. In order to control peritoneal carcinomatosis cytoreductive surgery to remove gross disease is combined with perioperative intraperitoneal and perioperative intravenous chemotherapy to eradicate microscopic residual disease. Chemotherapy agents are selected to be administered by the intraperitoneal or intravenous route based on their pharmacologic properties. A peritoneal- plasma barrier which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration is facilitated by moderate hyperthermia (41-42°C) of the intraperitoneal chemotherapy solution. A constant dose of chemotherapy agent and volume of carrier solution based on body surface area allows prediction of systemic drug exposure and systemic toxicity. Timing of the chemotherapy as a planned part of the surgical procedure to maximize exposure of all peritoneal surfaces is crucial to success.

Keywords: Intraperitoneal chemotherapy, 5-fluorouracil, doxorubicin, mitomycin C, peritoneal-plasma barrier, appendiceal cancer, colorectal cancer, peritoneal mesothelioma, ovarian cancer