The role of hyperthermic intraperitoneal intraoperative chemotherapy in ovarian cancer

Epithelial ovarian cancer (EOC) is the fourth most common gynecologic cancer in Europe and is the leading cause of death among women with gynecologic malignancies. This is due to the fact that the majority of the patients are diagnosed with advanced stage disease. In these stages, extensive intraperitoneal metastases are often present, making therapy more difficult. The current standard treatment involves primary or interval cytoreductive surgery and chemotherapy. However, many patients develop intraperitoneal (IP) recurrences despite complete surgery and chemotherapy. Therefore, alternative ways to deliver chemotherapy have been examined. Administration of the chemotherapy directly into the peritoneal cavity allows high doses of the cytotoxic agent at the site of the cancer, while minimizing the occurrence of systemic side effects. Theoretically, IP administration is most beneficial when only microscopic disease is present since penetration of the drug is limited to a few millimeters. IP chemotherapy can be administered during surgery under hyperthermic conditions (HIPEC) or during regular chemotherapy courses through a catheter placed into the abdominal cavity. IP administration results in an improved survival, although catheter-related morbidity is reported. Hyperthermia potentiates the cytotoxic effect of chemotherapy and may therefore have an additional positive effect on prognosis. Although recent observational studies show encouraging results with respect to effect on survival and rate of complications, it remains a challenge to identify those patients who would benefit most from adding HIPEC to the standard treatment. In this respect, age and timing of HIPEC during treatment might be important factors, although no convincing evidence is available yet. Currently, a total of 18 clinical trials are open and to answer the above-mentioned questions, it is adamant to complete these trials, especially the randomized phase III trials. Accrual is hampered by the fact that HIPEC is currently offered as standard treatment in some centers even though convincing evidence is not yet available. If these phase III trials show positive results in favor of HIPEC, subsequent trials comparing surgery and postoperative IP chemotherapy with surgery and HIPEC seem a logical next step.