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World J Obstet Gynecol. Nov 10, 2013; 2(4): 143-152
Published online Nov 10, 2013. doi: 10.5317/wjog.v2.i4.143
Pharmacology of cancer chemotherapy drugs for hyperthermic intraperitoneal peroperative chemotherapy in epithelial ovarian cancer
Kurt Van der Speeten, Anthony O Stuart, Paul H Sugarbaker
Kurt Van der Speeten, Department of Surgical Oncology, Ziekenhuis Oost-Limburg, 3600 Genk, Belgium
Kurt Van der Speeten, University Hasselt, Life Sciences Faculty, Oncology Research Cluster, 3000 Hasselt, Belgium
Anthony O Stuart, Paul H Sugarbaker, Washington Cancer Institute, Washington Hospital Center, Washington, DC 20010, United States
Author contributions: All authors contributed the data analysis and discussion of this review.
Correspondence to: Kurt Van der Speeten, MD, PhD, Department of Surgical Oncology, Ziekenhuis Oost-Limburg, Schiepse Bos 6, 3600 Genk, Belgium. kurt.vanderspeeten@zol.be
Telephone: +32-89-326524 Fax: +32-89-326524
Received: December 13, 2012
Revised: June 16, 2013
Accepted: June 23, 2013
Published online: November 10, 2013
Abstract

The peritoneal parietal and visceral surfaces of the abdomen and pelvis are an important anatomic site for the dissemination of epithelial ovarian cancer (EOC). The transcoelomic spread of cancer cells gives rise to peritoneal carcinomatosis (PC) which, without special treatments, is a fatal manifestation of EOC. In order to control PC cytoreductive surgery to remove macroscopic disease is combined with perioperative intraperitoneal (IP) and perioperative intravenous chemotherapy to eradicate microscopic residual disease. Chemotherapy agents are selected to be administered by the IP 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 IP chemotherapy solution. 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, Epithelial ovarian cancer, Ifosfamide, Cisplatin, Carboplatin, Taxanes, Pharmacokinetics, Pharmacodynamics

Core tip: Intraperitoneal (IP) chemotherapy is an important adjuvant treatment strategy in patients with advanced epithelial ovarian cancer. Although the clinical benefits have been demonstrated both in phase II and III trials, the pharmacologic rationale for this treatment strategy needs to be clarified. This manuscript reviews the pharmacokinetic and pharmacodynamic rationale of IP chemotherapy and analyzes the available data.