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Type: Journal article
Title: Clinical strategies to achieve an early and successful response to tyrosine kinase inhibitor therapy
Author: Hughes, T.
Hochhaus, A.
Citation: Seminars in Hematology, 2009; 46(2):S11-S15
Publisher: W B Saunders Co
Issue Date: 2009
ISSN: 0037-1963
Statement of
Timothy Hughes and Andreas Hochhaus
Abstract: Imatinib is the standard of care for previously untreated chronic myeloid leukemia (CML), with high response rates that lead to improved event-free and overall survival compared with interferon alfa. Imatinib dose is one important factor affecting response, and early clinical studies showed promising molecular response rates with high-dose therapy. Large, randomized trials are now ongoing to test this potential benefit and establish whether a starting dose of 800 mg/d improves long-term clinical outcomes compared with the current standard dose of 400 mg/d. Low plasma imatinib levels are associated with a decreased chance of response. The importance of imatinib dosing and plasma levels is likely due to their impact on intracellular concentrations of the drug. Cellular influx of imatinib is mediated by the OCT-1 protein, and patients with low OCT-1 activity may benefit from dose-intensive therapy. For nonresponding or slowly responding patients, dose escalation to 600 to 800 mg/d may lead to durable responses in patients with primary or secondary resistance. Regular monitoring of response is crucial to maximize therapeutic success, and improved understanding of the factors affecting response will guide future clinical strategies.
Keywords: Humans; Benzamides; Piperazines; Pyrimidines; Antineoplastic Agents; Protein Kinase Inhibitors; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Octamer Transcription Factor-1; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Imatinib Mesylate
Rights: Copyright © 2009 Elsevier Inc. All rights reserved.
RMID: 0020090633
DOI: 10.1053/j.seminhematol.2009.01.008
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Appears in Collections:Medicine publications

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