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

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      Publication Details (including relevant citation   information):

      Volume 43,   Number 5, 427-434, DOI: 10.1007/s002800050918


      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.

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