Mitomycin Dosing for HIPEC
Mitomycin is NOT the guideline-recommended agent for HIPEC in ovarian cancer—cisplatin at 75-100 mg/m² is the standard based on survival benefit data 1. However, mitomycin has established dosing protocols for other peritoneal malignancies when used off-guideline.
Guideline-Recommended Agent (Ovarian Cancer)
- Cisplatin 100 mg/m² is the National Comprehensive Cancer Network-endorsed standard for HIPEC in ovarian cancer, with demonstrated improvements in disease-free survival and overall survival 1.
- The dose range is 75-100 mg/m² based on guideline recommendations 1.
- Duration of perfusion is 90 minutes at 41-43°C for cisplatin protocols 1.
Mitomycin Dosing (When Used Off-Guideline)
If mitomycin is selected for non-ovarian peritoneal malignancies, the established dose is 35 mg/m² based on maximum tolerable dose studies 2.
Dose Determination
- A dose-escalation study established 35 mg/m² as the maximum tolerable dose, with unacceptable toxicity at 40 mg/m² 2.
- Earlier studies used concentration-based dosing of 10 mg/L in 6 liters of perfusate (total dose 60 mg, approximately 30-40 mg/m² for average body surface area) 3, 4, 5.
- Absolute doses of 45-60 mg have been used in colorectal peritoneal carcinomatosis 6.
Technical Parameters for Mitomycin HIPEC
- Perfusion duration: 90-120 minutes 3, 4, 5
- Inflow temperature: 46-49°C to achieve intra-abdominal temperature of 40-42°C 3, 4, 2
- Perfusate volume: 6 liters of peritoneal dialysate 3, 4, 5
- Delivery system: Closed circuit with 3 large-bore intraperitoneal catheters (28 French), two pumps, heat exchanger, and filters 6, 2
Critical Safety Considerations
- Systemic mitomycin toxicity can cause severe cytopenia and respiratory depression—this is a life-threatening complication 6.
- Mortality rates with mitomycin HIPEC range from 0-8%, with morbidity in 3-19% of patients 3, 4, 2, 5.
- General hypothermia to 32°C is used during the procedure to minimize systemic absorption 3, 4.
Disease-Specific Context
Colorectal Peritoneal Carcinomatosis
- Mitomycin 35 mg/m² has shown 2-year survival of 59% when complete cytoreduction is achieved 2.
- Median response duration is approximately 6 months 6.
Gastric Cancer with Peritoneal Carcinomatosis
- For stage 1-2 carcinomatosis (granulations <5 mm), 1-year survival was 80% with mitomycin HIPEC 5.
- For stage 3-4 disease (granulations >5 mm), outcomes are poor with only 10% 1-year survival 5.
Key Pitfalls to Avoid
- Do not use mitomycin doses exceeding 35 mg/m²—toxicity becomes unacceptable 2.
- Complete cytoreduction (residual disease <1 cm, ideally <2.5 mm) is mandatory before HIPEC, as incomplete cytoreduction negates survival benefits 7, 6.
- HIPEC should only be performed at high-volume experienced centers, as complication rates correlate inversely with institutional experience 7, 8.
- Patient selection is critical: Peritoneal Cancer Index <10-20, no extraperitoneal metastases, and good performance status are essential 7.