Hyperthermic intraperitoneal chemotherapy with cisplatin and mitomycin C for colorectal cancer peritoneal metastases: A systematic review of the literature

BACKGROUND: The randomized trial PRODIGE 7 failed to show the benefit of oxaliplatin hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal peritoneal metastasis treatment (CR PM). This systematic review focuses on the association of cisplatin (CDDP) with mitomycin C (MMC) in HIPEC in CR PM. CONTENT: Experimental studies demonstrated that hyperthermia, in addition to CDDP ± MMC treatment, gradually improved the cytotoxic effect by increasing early apoptosis, eATP interaction, intracellular CDDP concentration (by 20%) and p73 expression. Recent studies with highly selected patients reported unusual prolonged survival with a median overall survival (OS) of approximately 60 months, with a HIPEC combination of CDDP (25 mg/m(2)/L) plus MMC (3.3 mg/m(2)/L) at a temperature of 41.5–42.5 °C for 60–90 min. Major complications occurred in less than 30% of patients with limited hematological toxicity (less than 15%). In addition, in a phase 2 trial, an adjuvant HIPEC benefit was demonstrated in colorectal cancer patients with high risk for peritoneal failure (5-year OS: 81.3% vs. 70% for the HIPEC group vs. the control group, respectively, p=0.047). After a recurrence, an iterative procedure permitted similar recurrence-free disease (13 vs. 13.7 months) with an acceptable morbidity (18.7% of severe complications). SUMMARY AND OUTLOOK: The combination of CDDP and MMC seems to be an interesting protocol as an alternative to high-dose and short-term oxaliplatin.