Treatment of primary peritoneal mesothelioma by continuous hyperthermic peritoneal perfusion (CHPP)

Background: Primary peritoneal mesothelioma is a locally aggressive disease that is difficult to treat or even palliate. Continuous hyperthermic perit oneal perfusion (CHPP) with cisplatin (CDDP) allows uniform, high regional delivery of chemotherapeutics and hyperthermia to the peritoneal surface fo r the treatment of peritoneal tumors. This article summarizes the results o f 18 patients with peritoneal mesothelioma treated with CHPP. Methods: From June 1993 through April 1998, 18 patients with primary perito neal mesothelioma (13 male, 5 female; median age, 51 years) underwent surgi cal exploration and tumor debulking followed by a 90-minute CHPP with CDDP and hyperthermia as part of three consecutive phase I trials conducted at t he National Cancer Institute. Seventeen of 18 patients had malignant perito neal mesothelioma, 13 with associated ascites. One patient had a symptomati c, multiply recurrent, benign, cystic peritoneal mesothelioma. Three patien ts who had a recurrence after a prolonged progression-free interval (>6 mon ths) after CHPP underwent re-treatment. CHPP parameters included median cis platin dose of 530 mg (range, 187-816), perfusate volume 6.0 liter (range, 4-9), flow 1.5 liter/min (range, 1-2), intraperitoneal temperature 41 degre es C (range, 38.7-43.2), and central temperature 38.6 degrees C (range, 36. 8-39.7). Results: Median follow-up after CHPP is 19 months (range, 2-56) with no ope rative or treatment-related mortality. Overall operative morbidity was 24% and included two patients with superficial wound infection and one patient each with atrial fibrillation, pancreatitis, fascial dehiscence, ileus, lin e sepsis, and clostridium difficile colitis. The major treatment-related to xicity was systemic renal toxicity at doses above what was defined as the m aximum tolerated dose of cisplatin. Nine of 10 patients had resolution of t heir ascites postoperatively. Three patients who developed recurrent ascite s (27, 22, and 10 months after initial treatment) were re-treated and had r esolution of their ascites with ongoing responses at 24, 6, and 4 months af ter the second perfusion. The median progression-free survival was 26 month s, and the overall 2-year survival was 80%. The median overall survival has not been reached. Conclusions: CHPP with cisplatin can be performed safely with no mortality and minimal morbidity. In selected patients, successful palliation in the a bdomen and long-term survival, compared with historical controls, can be ac hieved with aggressive surgical debulking and CHPP. Re-treatment after init ial response can result in a second long-term response.