A feasibility, pharmacokinetic and frequency-escalation trial of intraperitoneal chemotherapy in high risk gastrointestinal tract cancer.
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.
Seymour
M T
MT
Cancer Research UK Centre, University of Leeds, Cookridge Hospital, Leeds, LS16 6QB, UK. matt.seymour@leedsth.nhs.uk
Trigonis
I
I
Finan
P J
PJ
Halstead
F
F
Dunham
R
R
Wilson
G
G
Farrugia
D
D
Chester
J D
JD
King
J
J
Brown
C B
CB
Slevin
M L
ML
Joel
S P
SP
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
D000970:Antineoplastic Agents; D002955:Leucovorin; D005472:Fluorouracil