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QS24. Results of a Phase II Randomized Comparison of Flat vs Weight based Mitomycin C Intraperitoneal Chemotherapy for Patients Undergoing Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy

Thursday, March 5, 2026
3:41 PM - 3:45 PM MST
Location: Upper GI/HPB/Colorectal HUB Zone
Introduction: Cytoreductive surgery (CRS) ± heated intraperitoneal chemotherapy (HIPEC) has demonstrated increased survival in patients with peritoneal carcinomatosis (PC) from advanced gastrointestinal (GI) malignancies. Mitomycin C (MMC) is historically the most common drug utilized worldwide with highly variable dosing and is associated with neutropenia and increased morbidity. Two dominant dosing strategies: flat dose (FD) and weight-based (WB) have never been compared, and lack of consensus in dosing prevents standardization of HIPEC technique.   


Methods: A single institution investigator-initiated phase II trial compared FD and WB MMC in patients undergoing CRS+HIPEC for advanced GI cancer. Eligible patients were randomized to MMC FD 40 mg vs WB 12.5 mg/m2 utilizing 1:1 allocation. Plasma (PLA) and peritoneal (PER) fluid samples were collected (at 0, 15, 30, 60, 90 min) in addition to PLA postoperatively (2, 4, 12 hr) for pharmacokinetic (PK) analysis including Cmax (ng/mL) and area under the curve (AUC) (hr*ng/mL).  Clinicopathologic data and rate of neutropenia (treatment) between the two arms were compared. Recurrence data was evaluated for all patients with ≥ 1 year follow-up, excluding those with LAMN and completeness of cytoreduction (CC) score = 2.   


Results: Of patients enrolled, 60 patients have undergone CRS and HIPEC and PK data has been analyzed for 54 of these, including 24 who received FD and 30 who received WB. MMC exposure was significantly higher in both PLA and PER for FD vs WB. Mean PLA Cmax was 675.2 (FD) vs 442.6 (WB), p = 0.0039. Mean PER Cmax was 13663 (FD) vs 9436 (WB), p = 0.023 (Figure 1A-B). Mean PLA AUC was 1385 hr*ng/mL (FD) vs 878.8 hr*ng/mL (WB), p = 0.0023. Mean PER AUC was 13044 hr*ng/mL (FD) vs 8464 hr*ng/mL for WB, p < 0.0001 (Figure 1C-D). No correlation existed between PER and PLA Cmax. The 2-week WBC nadir was higher in the FD arm; 4.78*103/µL (FD) vs 5.51*103/µL (WB), p = 0.09. Neutropenia treatment was required for a significantly greater proportion of patients in the FD arm; 17.8% (FD) vs 0% (WB), p = 0.006. There was no difference in 1-year disease free survival or overall survival between arms.  


Conclusions: The significantly higher MMC exposure in the FD group is associated with higher rates of neutropenia and no known survival benefit. Future directions include the creation of a population PK model from these analyses. 

Learning Objectives:

  • Discuss dosing strategies for heated intraperitoneal chemotherapy to treat peritoneal metastases from advanced GI malignancies.
  • Weigh the risks and benefits of using flat vs. weight based dosing for mitomycin C in heated intraperitoneal chemotherapy.