Effect of gastrointestinal resection on sunitinib exposure in patients with GIST

GIST patients often undergo GI-surgery. Previous studies have shown that imatinib and nilotinib exposures were decreased in GIST patients with prior major gastrectomy. We investigated whether major gastrectomy influences the exposure to sunitinib and its active metabolite SU12662. Pharmacokinetic da...

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Bibliographic Details
Published in:BMC cancer 2014-08, Vol.14 (1), p.575-575, Article 575
Main Authors: de Wit, Djoeke, van Erp, Nielka P, Khosravan, Reza, Wiltshire, Robin, Allred, Randy, Demetri, George D, Guchelaar, Henk-Jan, Gelderblom, Hans
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - pharmacokinetics
Clinical Trials as Topic
Female
Gastrectomy - adverse effects
Gastrointestinal Neoplasms - drug therapy
Gastrointestinal Neoplasms - surgery
Gastrointestinal Stromal Tumors - drug therapy
Gastrointestinal Stromal Tumors - surgery
Humans
Indoles - administration & dosage
Indoles - pharmacokinetics
Male
Middle Aged
Pyrroles - administration & dosage
Pyrroles - pharmacokinetics
Young Adult
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Summary:GIST patients often undergo GI-surgery. Previous studies have shown that imatinib and nilotinib exposures were decreased in GIST patients with prior major gastrectomy. We investigated whether major gastrectomy influences the exposure to sunitinib and its active metabolite SU12662. Pharmacokinetic data from 305 GIST patients included in 4 phase I-III trials were analyzed. Patients were subdivided into 6 groups according to their prior GI-surgery. Apparent clearance (CL/F) and dose-corrected steady-state plasma exposures (AUC24,ss) of sunitinib and SU12662 were estimated using a population PK approach. ANCOVA was performed to test for differences in AUC24,ss and CL/F between each surgery subgroup and controls. Major gastrectomy did not influence sunitinib or SU12662 exposure. The geometric mean of sunitinib and SU12662 AUC24,ss was decreased by 21% and 28% in patients with both gastrectomy and small bowel resection (n = 8) compared to controls (n = 63) for sunitinib (931 ng hr/mL (95%-CI; 676-1283) versus 1177 ng hr/mL (95%-CI; 1097-1263); p
ISSN:1471-2407
1471-2407
DOI:10.1186/1471-2407-14-575