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


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.
Van der Speeten
Kurt
K
Department of Surgical Oncology, Ziekenhuis Oost-Limburg, Genk, Belgium.
Stuart
O Anthony
OA
Chang
David
D
Mahteme
Haile
H
Sugarbaker
Paul H
PH
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D001063:Appendiceal Neoplasms / Q000188:drug therapy / Q000601:surgery; D002277:Carcinoma / Q000188:drug therapy* / Q000601:surgery / Q000628:therapy; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000601:surgery / Q000628:therapy; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D006979:Hyperthermia, Induced; D007274:Injections, Intraperitoneal; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000601:surgery / Q000628:therapy; D012186:Retroperitoneal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D055815:Young Adult
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D016685:Mitomycin; D005472:Fluorouracil