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Thyroid dysfunction caused by second-generation tyrosine kinase inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia

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Item Type:Article
Title:Thyroid dysfunction caused by second-generation tyrosine kinase inhibitors in Philadelphia chromosome-positive chronic myeloid leukemia
Creators Name:Kim, T.D. and Schwarz, M. and Nogai, H. and Grille, P. and Westermann, J. and Ploeckinger, U. and Braun, D. and Schweizer, U. and Arnold, R. and Doerken, B. and le Coutre, P.
Abstract:BACKGROUND: Thyroid dysfunction is a well-known adverse effect of first-generation tyrosine kinase inhibitors (TKIs), like sunitinib. The aim of this study was to investigate the effect of second-generation TKIs on thyroid function. METHODS: We retrospectively assessed the effect of the first-generation TKI imatinib and the second-generation TKI nilotinib and dasatinib on thyroid function tests in 73 Philadelphia chromosome-positive (Ph-positive) chronic myeloid leukemia patients. RESULTS: Overall, 33 of 73 (45%) had one or more thyroid function test abnormalities during follow-up. Hypothyroidism or hyperthyroidism were found in 18 of 73 (25%) and 21 of 73 (29%) cases after a median of 6 and 22 weeks, respectively. In most patients (29 of 39, 74%) thyroid dysfunction was transient without clinical symptoms. Therapy of hypo-/hyperthyroidism was required in three patients. Thyroid dysfunction never resulted in the discontinuation of TKI therapy. Under treatment with imatinib, nilotinib, and dasatinib, thyroid abnormalities were detected in 25%, 55%, and 70%, respectively. Four of 55 patients (7%) treated with nilotinib had evidence for an autoimmune thyroiditis (antibody positive in 3 of 4 patients) with an episode of hyperthyroidism preceding hypothyroidism. CONCLUSIONS: Thyroid dysfunction is a common adverse event with second-generation TKI therapy in patients with Ph-positive chronic myeloid leukemia. Although the mechanism is still unclear, the high frequency of thyroid abnormalities, including autoimmune thyroiditis, warrants regular and long-term monitoring of thyroid function in these patients.
Keywords:Antineoplastic Agents, BCR-ABL Positive Chronic Myelogenous Leukemia, Philadelphia Chromosome, Piperazines, Protein Kinase Inhibitors, Pyrimidines, Retrospective Studies, Thiazoles, Thyroid Diseases, Thyroid Function Tests, Thyroid Gland
Publisher:Mary Ann Liebert
Page Range:1209-1214
Date:9 November 2010
Official Publication:https://doi.org/10.1089/thy.2010.0251
PubMed:View item in PubMed

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