Hyperthermic intraperitoneal chemotherapy ( HIPEC ) in optimally cytoreduced peritoneal carcinomatosis of gynecology origin : Does it provide survival advantage ?

Among the gynecological malignancies, ovarian cancer is most frequently associated with diffuse peritoneal carcinomatosis. Rarely, peritoneal carcinomatosis is caused by other gynecological malignancies, including endometrial, fallopian tube and primary peritoneal cancer as well as malignant mixed mesodermal tumors. Despite progress in cytoreductive surgery and systemic chemotherapy and consequently significant improvement of survival in advanced ovarian cancer, still the majority of patients will ultimately die from this disease. Hence, besides development of novel more effective drugs, alternative routes of administration have been studied. Intraperitoneal chemotherapy is associated with a major pharmacokinetic advantage, with high locoregional drug concentrations and low systemic toxicity. Optimal cytoreductive surgery is a prerequisite because of its limited penetration depth. The addition of postoperative intraperitoneal instillation chemotherapy to the management of primary advanced ovarian Correspondence/Reprint request: Dr. Eelco de Bree, Department of Surgical Oncology, University Hospital, P.O. Box 1352, 71110 Herakleion, Greece. E-mail: [email protected] Eelco de Bree et al. 74 cancer has been demonstrated to be beneficial in randomized trials and meta-analysis. Intraoperative application of intraperitoneal chemotherapy has the advantage of improved distribution of the drug solution through the peritoneal cavity and exposure of the entire seroperitoneal surface to the agent. Moreover, intraoperatively it can be combined with hyperthermia by heating the drug solution. Intraperitoneal instillation of certain drugs and hyperthermia are both better tolerated when the patient is under general anesthesia. Hyperthermia is cytotoxic itself and enhances the efficacy of many chemotherapeutic drugs. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been demonstrated to be feasible and associated with acceptable morbidity. Unfortunately, there are no data from randomized trials available to asses its role in the management of gynecological malignancies with peritoneal dissemination. Cautious extrapolation of data from simple intraperitoneal instillation chemotherapy and data from phase II and non-randomized comparative studies suggest that HIPEC delivered at the time of surgery for ovarian cancer has definite potential. Further investigation is necessary and only a randomized trial design will adequately answer the question whether the addition of HIPEC actually prolongs survival in selected patients with peritoneal dissemination of ovarian and other gynecological cancer, conditions where outcome remains so poor with conventional therapy.