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A pharmacokinetic model and the clinical pharmacology of cis-platinum, 5-fluorouracil and mitomycin-C in isolated pelvic perfusion.

Abstract：

PURPOSE:An isolated pelvic perfusion technique using multiple agents was used both in patients with unresectable recurrent pelvic neoplasms and as a preoperative therapy for advanced pelvic malignancy. METHODS:The technique consisted of vascular occlusion via transfemoral balloon catheters, circulation and drug infusion using standard hemodialysis technology, and a 45-min isolation period. Blood and urine samples were analyzed for the levels of cis-platinum (17 patients, 21 courses of therapy, 50-100 mg/m2, infusion 0-10 min), 5-fluorouracil (12 patients, 14 courses, 1500 mg/m2, infusion 1/3 dose 0-1 min, 2/3 dose 1-20 min) and mitomycin-C (11 patients, 14 courses, 10-20 mg/m2, infusion 10-20 min). An empirical, four-compartment pharmacokinetic model was developed to establish drug distribution curves for the pelvic and systemic circulations and to yield valid estimates of the pharmacokinetic parameters. RESULTS:Pelvic isolation of drug was demonstrated by the pelvic-systemic drug exposure ratios of 6.0:1 for cis-platinum, 8.4:1 for 5-fluorouracil and 9.0:1 for mitomycin-C. Isolation at the L3-4 interspace resulted in minor urine drug elimination during isolation (cis-platinum 7.2% of drug, 5-fluorouracil 2.4% and mitomycin-C 2.5%). Because drug infusion was limited to the first 20 min of isolation, drug levels at the end of the isolation period were reduced to the extent that no extracorporeal drug removal mechanism was needed. CONCLUSION:These pharmacokinetic results indicate that this isolation technique has the potential to provide increased therapeutic indices and is a suitable system for evaluating fast-acting highly toxic experimental drugs to human pelvic cancers which are poorly responsive to conventional clinical protocols.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Wanebo HJ,Belliveau JF

doi

10.1007/s002800050918

keywords:

subject

Has Abstract

pub_date

1999-01-01 00:00:00

pages

427-34

issue

eissn

0344-5704

issn

1432-0843

journal_volume

pub_type

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A pharmacokinetic model and the clinical pharmacology of cis-platinum, 5-fluorouracil and mitomycin-C in isolated pelvic perfusion.