Changes induced by surgical and clinical factors in the pharmacology of intraperitoneal mitomycin C in 145 patients with peritoneal carcinomatosis

Cancer Chemother Pharmacol. 2011 Jul;68(1):147-56. doi: 10.1007/s00280-010-1460-4. Epub 2010 Sep 21.

Abstract

Background: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are a combined treatment modality considered for selected patients with peritoneal carcinomatosis from colorectal and appendiceal cancer. Mitomycin C is a drug often used in this clinical setting. The surgical and clinical factors that may influence the pharmacokinetics of hyperthermic intraperitoneal chemotherapy should be further elucidated.

Materials and methods: The patients included were 145 who had colorectal or appendiceal carcinomatosis resected using cytoreductive surgery prior to treatment with hyperthermic intraperitoneal chemotherapy with mitomycin C as part of a multidrug regimen. The effect of clinical and surgical factors on drug distribution after single intraperitoneal bolus administration with mitomycin C was determined.

Results: The pharmacokinetics of 145 patients treated with intraperitoneal mitomycin C showed a 27 times greater exposure to peritoneal surfaces when compared to plasma. At 90 min, 29% of the drug remained in the chemotherapy solution, 62% was retained in the body, and 9% was excreted in the urine. The extent of peritonectomy increased the clearance of mitomycin C from the peritoneal space (p = 0.051). A major resection of visceral peritoneal surface and a contracted peritoneal space reduced drug clearance. A contracted peritoneal space significantly reduced (p = 0.0001) drug concentrations in the plasma.

Conclusions: Surgical and clinical factors may require modifications of drug dose or timing of chemotherapy administration. A large visceral resection and a contracted peritoneal space caused a reduced mitomycin C clearance. Total diffusion surface is an important determinant of mitomycin C pharmacokinetics.

MeSH terms

  • Adult
  • Aged
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / blood
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / pharmacology*
  • Antimetabolites, Antineoplastic / administration & dosage
  • Antimetabolites, Antineoplastic / metabolism
  • Antimetabolites, Antineoplastic / pharmacology
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacology
  • Appendiceal Neoplasms / drug therapy
  • Appendiceal Neoplasms / surgery
  • Carcinoma / drug therapy*
  • Carcinoma / surgery
  • Carcinoma / therapy
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / surgery
  • Colorectal Neoplasms / therapy
  • Combined Modality Therapy
  • Female
  • Fluorouracil / administration & dosage
  • Fluorouracil / metabolism
  • Fluorouracil / pharmacology
  • Humans
  • Hyperthermia, Induced
  • Injections, Intraperitoneal
  • Male
  • Middle Aged
  • Mitomycin / administration & dosage*
  • Mitomycin / blood
  • Mitomycin / pharmacokinetics
  • Mitomycin / pharmacology
  • Peritoneal Neoplasms / drug therapy*
  • Peritoneal Neoplasms / surgery
  • Peritoneal Neoplasms / therapy
  • Retroperitoneal Neoplasms / drug therapy*
  • Retroperitoneal Neoplasms / surgery
  • Young Adult

Substances

  • Antibiotics, Antineoplastic
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Mitomycin
  • Fluorouracil