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. 2025 Oct 21;51(12):110534.
doi: 10.1016/j.ejso.2025.110534. Online ahead of print.

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

Giancarlo Sticca  1 , Mikael Soucisse  2 , Maria Abou-Khalil  3 , Mai-Kim Gervais  4 , Jean-François Tremblay  5 , Pierre Dubé  6 , Lucas Sideris  7
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Free article

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

Giancarlo Sticca et al. Eur J Surg Oncol. .
Free article

Abstract

Goals: 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are the primary HIPEC agents for colorectal and appendiceal PM, previous studies comparing both agents relied on outdated low-dose MMC regimens.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.

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

Results: 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).

Conclusion: 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.

Keywords: HIPEC; High dose mitomycin C; Oxaliplatin; Peritoneal metastases; Postoperative complications; Toxicity.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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