Portal de Periódicos da CAPES

Pharmacokinetic analysis of irinotecan plus bevacizumab in patients with advanced solid tumors

2009; Springer Science+Business Media; Volume: 65; Issue: 1 Linguagem: Inglês

10.1007/s00280-009-1008-7

1432-0843

Crystal S. Denlinger, Rebecca Blanchard, Lu Xu, Coen Bernaards, Samuel Litwin, Cynthia Spittle, Daniel Berg, Susan McLaughlin, Maryann Redlinger, Andrew Dorr, Julie Hambleton, Scott N. Holden, A. Kearns, Sara Kenkare-Mitra, Bert L. Lum, Neal J. Meropol, Peter J. O’Dwyer,

Lung Cancer Research Studies

The purpose of this study was to evaluate the effect of bevacizumab on the pharmacokinetics (PK) of irinotecan and its active metabolite. Exploratory analyses of the impact of variability in uridine diphosphate glucuronosyltransferase 1A (UGT1A) genes on irinotecan metabolism and toxicity were conducted. This was an open-labeled, fixed-sequence study of bevacizumab with FOLFIRI (irinotecan, leucovorin, and infusional 5-fluorouracil). Pharmacokinetic assessments were conducted in cycles 1 and 3. Forty-five subjects were enrolled. No difference in dose-normalized AUC0–last for irinotecan and SN-38 between irinotecan administered alone or in combination with bevacizumab was identified. Leukopenia was associated with higher exposure to both irinotecan and SN-38. UGT1A1 polymorphisms were associated with variability in irinotecan PK. Gastrointestinal toxicity was associated with UGT1A6 genotype. No other associations between UGT1A genotypes and toxicity were detected. Bevacizumab does not affect irinotecan PK when administered concurrently. A variety of pharmacogenetic relationships may influence the pharmacokinetics of irinotecan and its toxicity.