Oncotarget

Clinical Research Papers:

Effects of first- and second-generation tyrosine kinase inhibitor therapy on glucose and lipid metabolism in chronic myeloid leukemia patients: a real clinical problem?

Alessandra Iurlo _, Emanuela Orsi, Daniele Cattaneo, Veronica Resi, Cristina Bucelli, Nicola Orofino, Mariarita Sciumè, Chiara Elena, Valeria Grancini, Dario Consonni, Ester Maria Orlandi and Agostino Cortelezzi

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Oncotarget. 2015; 6:33944-33951. https://doi.org/10.18632/oncotarget.5580

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Abstract

Alessandra Iurlo1,2, Emanuela Orsi3, Daniele Cattaneo1, Veronica Resi3, Cristina Bucelli1, Nicola Orofino1, Mariarita Sciumè1, Chiara Elena4, Valeria Grancini3, Dario Consonni5, Ester Maria Orlandi4 and Agostino Cortelezzi1

1 Oncohematology Division, IRCCS Ca’ Granda – Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy

2 Oncohematology Unit of the Elderly, IRCCS Ca’ Granda – Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy

3 Endocrinology and Diabetes Unit, Department of Medical Sciences, IRCCS Ca’ Granda – Maggiore Policlinico Hospital Foundation, and University of Milan, Milan, Italy

4 Oncology-Hematology Department, Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

5 Epidemiology Unit, Department of Preventive Medicine, IRCCS Ca’ Granda – Maggiore Policlinico Hospital Foundation, Milan, Italy

Correspondence to:

Alessandra Iurlo, email:

Keywords: chronic myeloid leukemia, imatinib, dasatinib, nilotinib, diabetes mellitus, metabolic syndrome

Received: June 18, 2015 Accepted: August 21, 2015 Published: September 10, 2015

Abstract

Background: Tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of patients with chronic myeloid leukemia (CML). They have a distinct toxicity profile that includes glycometabolic alterations: i.e. diabetes mellitus (DM), impaired fasting glucose (IFG), and the metabolic syndrome (MS). The aim of this study was to evaluate the prevalence of these alterations in a cohort of CML-chronic phase patients treated with imatinib, dasatinib or nilotinib.

Methods: The study involved 168 consecutive CML-chronic phase patients with no history of DM/IFG or MS. Anthropometric and metabolic parameters were assessed, and DM/IFG and MS were diagnosed based on the criteria of the American Diabetes Association and the National Cholesterol Education Program-Adult Treatment Panel III, respectively.

Results: The nilotinib group had significantly higher levels of fasting plasma glucose, insulin, C-peptide, insulin resistance, and total and LDL cholesterol than the imatinib and dasatinib groups. DM/IFG were identified in 25% of the imatinib- and dasatinib-treated patients, and 33% of those in the nilotinib cohort (p = 0.39 vs imatinib and p = 0.69 vs dasatinib). A diagnosis of MS was made in 42.4% of the imatinib-treated patients, 37.5% of the dasatinib-treated patients, and 36.1% of the nilotinib-treated patients (p = 0.46 vs imatinib and p = 0.34 vs dasatinib).

Conclusions: Treatment with nilotinib does not seem to induce DM/IFG or the MS to a significantly higher extent than imatinib or dasatinib, though it causes a worse glycometabolic profile. These findings suggest the need for a close monitoring of glucose and lipid metabolism and a multidisciplinary approach in patients treated with nilotinib.


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