Surgically directed chemotherapy: heated intraperitoneal lavage with mitomycin C

Area of Science:

• Oncology
• Surgical Oncology
• Pharmacology

Background:

• Advanced gastrointestinal cancers often present with peritoneal carcinomatosis.
• Cytoreductive surgery is a key component in managing these advanced stages.
• Novel drug delivery methods are needed to improve treatment efficacy and reduce systemic toxicity.

Purpose of the Study:

• To evaluate the pharmacokinetics of mitomycin C (MMC) administered via hyperthermic intraperitoneal lavage.
• To assess the toxicities and adverse reactions associated with this treatment modality.
• To determine the feasibility of this approach in patients with advanced gastrointestinal malignancies.

Main Methods:

• A hyperthermic (42°C) intraperitoneal lavage with mitomycin C (30 mg/3 L) was performed for 2 hours post-cytoreductive surgery.
• Pharmacokinetic data were collected from 10 patients, and adverse reactions were recorded in 20 patients.
• Abdominal massage was used to ensure adequate drug distribution throughout the peritoneal cavity.

Main Results:

• Approximately 70% (21 mg) of the administered mitomycin C was absorbed from the perfusate.
• Median peak blood levels of MMC reached 0.25 µg/ml, observed at 45-60 minutes.
• Morbidity was low, primarily consisting of surgical complications and mild to moderate myelosuppression.

Conclusions:

• Hyperthermic intraperitoneal mitomycin C lavage demonstrates favorable pharmacokinetics and an acceptable toxicity profile.
• This method of drug delivery warrants further investigation in phase II clinical trials for advanced gastrointestinal cancers.
• The combination of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy offers a potential therapeutic advancement.