No satisfactory treatment exists for disseminated intraperitoneal malignancies. This manifestation of advanced cancer has a poor survival and a dismal quality of life. Recent in vitro data has suggested that heat, in combination with various chemotherapeutic agents, including mitomycin C (MMC), has synergistic cytotoxicity against a variety of human cancer cell lines. Our preliminary clinical research has demonstrated that cytoreductive surgery, followed by intraperitoneal hyperthermic chemotherapy (IPHC) with MMC, is well-tolerated and perhaps effective (prolonged survival, eradication of ascites) in the treatment of peritoneal carcinomatosis. Our proposed Phase I-Il clinical studies will evaluate the safety, efficacy, and impact on quality of life of this novel treatment: cytoreductive surgery followed by IPHC with MMC. During the Phase l study, patients with histologically-proven malignancies of gastrointestinal or ovarian origin confined to the peritoneal cavity are eligible. Only patients with peritoneal carcinomatosis of gastrointestinal origin are eligible for the Phase Il study. During the Phase I-Il studies, patients will undergo cytoreductive surgery followed by a two-hour, heated peritoneal perfusion of MMC. The maximally tolerated perfusion inflow temperature (MMC dose is fixed at 40 mg) identified during the Phase l study will be used in ali Phase Il Study patients. During both study phases the peritoneal, plasma, and urinary pharmacokinetics of MMC will be determined. Outcome measures to be compared with pre-operative baseline studies include the presence of cytology positive cells in peritoneal washings, concentrations of serum tumor markers, presence of ascites, quality of life, and survival. Our proposed studies will assist in the development of a novel therapy which may have a positive impact on the long-term survival and quality of life in patients with peritoneal carcinomatosis of gastrointestinal origin.
