Two Decades of Progress in the Management of a Rare Disease—Peritoneal Mesothelioma

Abstract

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare but aggressive disease with a poor sustained response to systemic chemotherapy. Historically, the median survival has been less than 1 year. The disease rarely disseminates outside of the peritoneal space suggesting that local-regional treatment options may be effective in the long-term control of this malignancy. Establishment of a referral center to concentrate experience with the management of this disease has contributed greatly to progress in its management.Materials and methods:Through a series of Institutional Review Board-approved protocols, a long-standing morbidity/mortality assessment, numerous manuscripts published in the peer-reviewed literature, and participation in numerous national and international workshops, a new standard of care with expectations of long-term survival in a majority of patients has evolved.Results:The surgery for this disease has evolved through a sequence of peritonectomy procedures and visceral resections whose goal is to remove all visible evidence of disease. The first step in successful treatment is a complete cytoreduction. After the cancer resection in the operating room, hyperthermic perioperative chemotherapy (HIPEC) is used. A three-drug protocol combines heat-augmented chemotherapy within the peritoneal space and systemic chemotherapy that is heat-augmented as a continuous infusion intravenously. Catheters are placed for early postoperative intraperitoneal chemotherapy using paclitaxel for 5 days. Also placed at the time of the cytoreductive surgery is an intraperitoneal port for long-term combined intraperitoneal and systemic chemotherapy using cisplatin and pemetrexed for 6 months. Patients having the long-term bidirectional chemotherapy have shown statistically significant improved survival compared with those patients who had surgery alone plus the perioperative chemotherapy. There have been no mortality and the grade 4 adverse events have been prospectively accumulated as 12 %.Conclusions:With continued effort, the surgery and long-term regional chemotherapy for DMPM has continued to improve over 20 years. Currently, a management plan that involves cytoreductive surgery, perioperative chemotherapy, and long-term bidirectional chemotherapy has changed the natural history of this disease. A global registry has been initiated to confirm the benefits of these extended treatments.