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

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.

• Authors: Kurt Van der Speeten, O Anthony Stuart, David Chang, Haile Mahteme, Paul H Sugarbaker
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 68 Issue 1 Pg. 147-56 (Jul 2011) ISSN: 1432-0843 [Electronic] Germany
• PMID: 20857115 (Publication Type: Journal Article)

Chemical References

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

Topics

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