Journal article
Pharmacokinetic Analysis of Irinotecan Plus Bevacizumab in Patients with Advanced Solid Tumors
Cancer chemotherapy and pharmacology, Vol.65(1), pp.97-105
12/2009
DOI: 10.1007/s00280-009-1008-7
PMCID: PMC2746259
PMID: 19415281
Abstract
Purpose
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.
Methods
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.
Results
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.
Conclusion
Bevacizumab does not affect irinotecan PK when administered concurrently. A variety of pharmacogenetic relationships may influence the pharmacokinetics of irinotecan and its toxicity.
Details
- Title: Subtitle
- Pharmacokinetic Analysis of Irinotecan Plus Bevacizumab in Patients with Advanced Solid Tumors
- Creators
- Crystal S Denlinger - Fox Chase Cancer Center, Philadelphia, PennsylvaniaRebecca Blanchard - Fox Chase Cancer Center, Philadelphia, PennsylvaniaLu Xu - Genentech, Inc., South San Francisco, CaliforniaCoen Bernaards - Genentech, Inc., South San Francisco, CaliforniaSamuel Litwin - Fox Chase Cancer Center, Philadelphia, PennsylvaniaCynthia Spittle - Fox Chase Cancer Center, Philadelphia, PennsylvaniaDaniel J Berg - University of Iowa, Iowa City, IowaSusan McLaughlin - Fox Chase Cancer Center, Philadelphia, PennsylvaniaMaryann Redlinger - University of Pennsylvania, Philadelphia, PennsylvaniaAndrew Dorr - Genentech, Inc., South San Francisco, CaliforniaJulie Hambleton - Genentech, Inc., South San Francisco, CaliforniaScott Holden - Genentech, Inc., South San Francisco, CaliforniaAnne Kearns - Genentech, Inc., South San Francisco, CaliforniaSara Kenkare-Mitra - Genentech, Inc., South San Francisco, CaliforniaBert Lum - Genentech, Inc., South San Francisco, CaliforniaNeal J Meropol - Fox Chase Cancer Center, Philadelphia, PennsylvaniaPeter J O'Dwyer - University of Pennsylvania, Philadelphia, Pennsylvania
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.65(1), pp.97-105
- DOI
- 10.1007/s00280-009-1008-7
- PMID
- 19415281
- PMCID
- PMC2746259
- NLM abbreviation
- Cancer Chemother Pharmacol
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Language
- English
- Date published
- 12/2009
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094389702771
Metrics
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