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World J Gastrointest Oncol. Jan 15, 2010; 2(1): 19-30
Published online Jan 15, 2010. doi: 10.4251/wjgo.v2.i1.19
Pharmacologic rationale for treatments of peritoneal surface malignancy from colorectal cancer
Paul H Sugarbaker, Kurt Van der Speeten, O Anthony Stuart
Paul H Sugarbaker, O Anthony Stuart, Washington Cancer Institute, Washington Hospital Center, Washington, DC 20010, United States
Kurt Van der Speeten, Department of Surgical Oncology, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600 Genk, Belgium
Author contributions: Sugarbaker PH, Stuart OA and Van der Speeten K performed the research; Sugarbaker PH, Stuart OA and Van der Speeten K analyzed the data; Sugarbaker PH, Stuart OA and Van der Speeten K wrote the paper.
Correspondence to: Paul H Sugarbaker, MD, FACS, FRCS, Washington Cancer Institute, Washington Hospital Center, 106 Irving St., NW, Suite 3900, Washington, DC 20010, United States. paul.sugarbaker@medstar.net
Telephone: +1-202-8773908 Fax: +1-202-8778602
Received: July 2, 2009
Revised: August 28, 2009
Accepted: September 5, 2009
Published online: January 15, 2010
Abstract

The peritoneal surfaces of the abdomen and pelvis are important sites for the dissemination of gastrointestinal and gynecologic malignancy. Transcoelomic dissemination of cancer cells gives rise to carcinomatosis, which, without special treatment, is a fatal manifestation of these diseases. To treat peritoneal carcinomatosis, cytoreductive surgery removes gross disease plus perioperative intraperitoneal and perioperative intravenous chemotherapy eradicates microscopic residual disease and chemical compatibilities. Chemotherapy agents are administered either 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 of the intraperitoneal chemotherapy is facilitated by moderate hyperthermia (41-42°C). Targeting of intravenous chemotherapy to the peritoneal surface is facilitated by the intraperitoneal heat. 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 hyperthermic chemotherapy as a scheduled part of the surgical procedure to uniformly expose 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