Bailey, Dennis B.;
Rassnick, Kenneth M.;
Dykes, Nathan L.;
Pendyala, Lakshmi
Phase I evaluation of carboplatin by use of a dosing strategy based on a targeted area under the platinum concentration-versus-time curve and individual glomerular filtration rate in cats with tumors
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Media type:
E-Article
Title:
Phase I evaluation of carboplatin by use of a dosing strategy based on a targeted area under the platinum concentration-versus-time curve and individual glomerular filtration rate in cats with tumors
Contributor:
Bailey, Dennis B.;
Rassnick, Kenneth M.;
Dykes, Nathan L.;
Pendyala, Lakshmi
Published:
American Veterinary Medical Association (AVMA), 2009
Published in:
American Journal of Veterinary Research, 70 (2009) 6, Seite 770-776
Language:
Not determined
DOI:
10.2460/ajvr.70.6.770
ISSN:
0002-9645
Origination:
Footnote:
Description:
AbstractObjective—To determine whether a carboplatin dose calculation that is based on a targeted area under the concentration-versus-time curve (AUCTarget) and individual glomerular filtration rate (GFR) accurately predicts carboplatin-associated myelotoxicoses in tumor-bearing cats, and to determine the maximum tolerated AUCTarget.Animals—32 cats with tumors.Procedures—In each cat, plasma clearance of technetium Tc 99m-labeled diethylenetriaminepentaacetic acid was measured to assess GFR. Carboplatin was administered IV. The dose was calculated by use of an equation as follows: Dose = AUCTarget × 2.6 × GFR × body weight. Initial AUCTarget was 2.0 min·mg·mL−1 and was increased in increments of 0.50 min·mg·mL−1 in cohorts of 3 cats. To assess myelotoxic effects, CBCs were performed weekly for ≥ 4 weeks. Following identification of the maximum tolerated AUCTarget, additional cats were treated at that AUCTarget and plasma platinum concentrations were measured in 6 cats.Results—The AUCTarget values ranged from 2.0 to 3.0 min·mg·mL−1. Neutropenia was the dose-limiting toxicosis, and the maximum tolerated AUCTarget was 2.75 min·mg·mL−1. Nineteen cats received this dose of carboplatin; 13 became neutropenic, but only 1 developed severe neutropenia (< 500 neutrophils/μL), and none had neutropenia-associated clinical signs. In the cats that had plasma platinum concentration determined, the difference between AUCTarget and the measured value ranged from −0.23 to 0.31 min·mg·mL−1 (median, 0.20 min·mg·mL−1).Conclusions and Clinical Relevance—In cats, carboplatin-associated myelotoxicoses were accurately and uniformly predicted by use of the proposed dosing strategy. The maximum tolerated AUCTarget for a single dose of carboplatin was 2.75 min·mg·mL−1.