Safety of high-dose mitomycin C vs oxaliplatin HIPEC for peritoneal metastases

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) improve survival in patients with peritoneal metastases (PM). While mitomycin-C (MMC) and oxaliplatin are the primary HIPEC agents for colorectal and appendiceal PM, previous studies comparing both agents relied on outdated low-dose MMC regimens. This study evaluates the safety of high-dose 35 mg/m² mitomycin C vs 460 mg/m² oxaliplatin.

This retrospective cohort study analyzed all patients with appendiceal and colorectal PM treated at a tertiary-care hospital from 2014 to 2024.

Among 282 patients, 48 (17.0 %) received high-dose MMC and 234 (83.0 %) received oxaliplatin. Patient demographics and oncological characteristics were similar (p > 0.05). High-dose MMC had significantly more toxic events (35.4 % vs 14.1 %, p < 0.001), greater CTCAE median toxicity grade (2 vs 1, p < 0.001), higher hepatic cytolysis (2.1 % vs 0.0 %, p = 0.027), increased neutropenia (27.1 % vs 4.3 %, p < 0.001), more gastric perforations (4.2 % vs 0 %, p = 0.002) as well as one case of HIPEC toxicity-related death due to neutropenic enterocolitis (2.1 % vs 0.0 %, p = 0.380). Oxaliplatin resulted in more hematomas (12.0 % vs 2.1 %, p = 0.040), higher need for parenteral nutrition (94.0 % vs 83.3 %, p = 0.012), and longer duration of nutritional support (12.3d vs 8.6d, p = 0.020). High-dose MMC had higher abdominal sepsis rates (6.3 % vs 1.3 %, p = 0.030). Severe complications, reintervention, ICU transfers, and 90-day mortality were similar (p > 0.05). Length of stay was shorter for high-dose MMC (14.7d vs 17.7d, p = 0.031).

High-dose MMC was associated with increased HIPEC toxicity, primarily neutropenia-related. Clinicians must balance the benefits and drawbacks of high-dose MMC and oxaliplatin to provide an optimal and individualized treatment.