title: Prolonged intraperitoneal infusion of 5-fluorouracil using a novel carrier solution.
abstract: A novel peritoneal carrier solution, Icodextrin 20 (7.5%), has allowed exploration of prolonged, intraperitoneal (i.p.) infusion of the cytotoxic drug 5-fluorouracil (5-FU). A phase I and pharmacokinetic study was performed to determine the toxicities and maximum tolerated dose of prolonged and continuous intraperitoneal 5-FU in patients with peritoneal carcinomatosis. Seventeen patients were entered into this study. Each patient had a Tenckhoff catheter placed into the peritoneal cavity under general anaesthetic. After initial flushing and gradual increase in exchange volumes with Icodextrin 20, 5-FU was administered daily from Monday to Friday, 50% as a bolus in the exchange bag and 50% in an elastomeric infusor device delivering continuous 5-FU to the peritoneal cavity at 2 ml h-1. Treatment was continued for 12 weeks or until intolerable toxicity developed. Abdominal pain and infective peritonitis proved to be the main dose-limiting toxicities. Initial problems with infective peritonitis were overcome by redesign of the delivery system, and it proved possible to deliver 300 mg m-2 5-FU daily (5 days per week) for 12 weeks. Pharmacokinetic studies showed i.p. steady-state 5-FU concentrations (mean 47 500 ng ml-1) that were > 1000-fold higher than systemic venous levels (mean 30 ng ml-1).
authors.affiliation: CRC Institute for Cancer Studies, University of Birmingham, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Kerr
authors.forename: A M
authors.initials: AM
authors.lastname: Young
authors.forename: J P
authors.initials: JP
authors.lastname: Neoptolemos
authors.forename: M
authors.initials: M
authors.lastname: Sherman
authors.forename: P
authors.initials: P
authors.lastname: Van-Geene
authors.forename: A
authors.initials: A
authors.lastname: Stanley
authors.forename: D
authors.initials: D
authors.lastname: Ferry
authors.forename: J W
authors.initials: JW
authors.lastname: Dobbie
authors.forename: B
authors.initials: B
authors.lastname: Vincke
authors.forename: J
authors.initials: J
authors.lastname: Gilbert
authors.forename: D
authors.initials: D
authors.lastname: el Eini
authors.forename: N
authors.initials: N
authors.lastname: Dombros
authors.forename: G
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000295:instrumentation*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005500:Follow-Up Studies; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis / Q000379:methods; D010534:Peritoneal Neoplasms / Q000188:drug therapy*
chemical_list: D000964:Antimetabolites, Antineoplastic; D004337:Drug Carriers; D005472:Fluorouracil