Purpose: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is now a recognized treatment for peritoneal carcinomatosis (PC). The objective of this phase I study is to determine the maximum tolerated dose of irinotecan (CPT-11) when used with mitomycin C (MMC) for closed abdomen HIPEC.
Methods: Patients with PC fulfilling the inclusion criteria were studied. All underwent cytoreductive surgery and closed abdomen HIPEC with 0.7 mg/kg MMC and an escalating dose of irinotecan. Grade 4 (National Cancer Institute grading system) surgical and hematological complications were used to identify dose-limiting toxicity (DLT).
Results: 12 patients were studied. At the first dose level of irinotecan (100 mg/m(2)), one patient developed a grade 4 hematological toxicity. Three other patients were included at the same level with no toxicity. Three patients were then included at the second dose level (150 mg/m(2) irinotecan), of whom one developed a grade 4 surgical complication. Three further patients were thus included at the second dose level. Of these three, two patients developed DLT [grade 4 neutropenia in one, grade 4 neutropenia and thrombocytopenia with an intra-abdominal lymphatic fistula requiring reoperation (grade 4 surgical complication) in the other]. Dose escalation was stopped at this level. The maximum tolerated dose of irinotecan was determined to be 100 mg/m(2).
Conclusion: Closed HIPEC combining MMC and irinotecan is safe and feasible. For HIPEC, the maximum tolerated dose of irinotecan is 100 mg/m(2) when used with 0.7 mg/kg MMC.