A feasibility, pharmacokinetic and frequency-escalation trial of intraperitoneal chemotherapy in high risk gastrointestinal tract cancer

Seymour, M. T., Trigonis, I., Finan, P. J., Halstead, F., Dunham, R., Wilson, G., Farrugia, D., Chester, John D. ORCID: https://orcid.org/0000-0002-7830-3840, King, J., Brown, C. B., Slevin, M. L. and Joel, S. P. 2008. A feasibility, pharmacokinetic and frequency-escalation trial of intraperitoneal chemotherapy in high risk gastrointestinal tract cancer. European Journal of Surgical Oncology (EJSO) 34 (4) , pp. 403-409. 10.1016/j.ejso.2007.05.007

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Abstract

Aims 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/m2 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. Conclusion 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	Colonic neoplasms; Stomach neoplasms; Fluorouracil; Leucovorin; Intraperitoneal drug therapy
Publisher:	Elsevier
ISSN:	0748-7983
Last Modified:	19 Oct 2022 08:43
URI:	https://orca.cardiff.ac.uk/id/eprint/18831

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