title: A feasibility, pharmacokinetic and frequency-escalation trial of intraperitoneal chemotherapy in high risk gastrointestinal tract cancer.
abstract: OBJECTIVE
  To assess the feasibility, pharmacokinetics and maximum tolerable frequency (MTF) of intraperitoneal (IP) 5-fluorouracil and leucovorin (FU/LV) added, as a regional boost, to intravenous chemotherapy after resection of gastrointestinal cancer.
  
  
  METHODS
  Fifty-three patients were recruited following gastrointestinal cancer resection (43 colon; 10 stomach/small bowel) with serosal involvement. Peritoneal ports were implanted and IP fluid distribution evaluated ultrasonically. Twelve patients were studied for pharmacokinetics; 44 (41 evaluable) for MTF. Treatment was weekly intravenous bolus FU/LV for 6 months; to this was added IP FU/LV (400/20 mg/m(2) in 1500 ml 4% icodextrin) with increasing frequency from 4 weekly to 1 weekly in four successive cohorts.
  
  
  RESULTS
  Peritoneal fluid distribution was excellent. Intraperitoneal FU exposure (AUC) after IP treatment was >1000-fold plasma AUC after IP treatment (regional pharmacokinetic advantage), and >100-fold plasma AUC after intravenous treatment (regional therapeutic advantage). IP therapy was well tolerated if given every 4, 3 or 2 weeks, but not weekly: 11/13, 7/8, 10/13 and 0/7 patients respectively completed treatment without IP modification in these cohorts. Problems with peritoneal access occurred in 20% of patients.
  
  
  CONCLUSIONS
  Adding fortnightly IP FU/LV to a standard intravenous regimen is safe, tolerable and provides high peritoneal FU exposure. More reliable peritoneal access is needed to improve the feasibility of this otherwise promising therapeutic approach.
authors.affiliation: Cancer Research UK Centre, University of Leeds, Cookridge Hospital, Leeds, LS16 6QB, UK. matt.seymour@leedsth.nhs.uk
authors.forename: M T
authors.initials: MT
authors.lastname: Seymour
authors.forename: I
authors.initials: I
authors.lastname: Trigonis
authors.forename: P J
authors.initials: PJ
authors.lastname: Finan
authors.forename: F
authors.initials: F
authors.lastname: Halstead
authors.forename: R
authors.initials: R
authors.lastname: Dunham
authors.forename: G
authors.initials: G
authors.lastname: Wilson
authors.forename: D
authors.initials: D
authors.lastname: Farrugia
authors.forename: J D
authors.initials: JD
authors.lastname: Chester
authors.forename: J
authors.initials: J
authors.lastname: King
authors.forename: C B
authors.initials: CB
authors.lastname: Brown
authors.forename: M L
authors.initials: ML
authors.lastname: Slevin
authors.forename: S P
authors.initials: SP
authors.lastname: Joel
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002955:Leucovorin; D005472:Fluorouracil