Publication:
Pioglitazone together with imatinib in chronic myeloid leukemia: A proof of concept study

Issued Date

2017-05-15

Resource Type

Article

ISSN

10970142
0008543X

DOI

10.1002/cncr.30490

Other identifier(s)

2-s2.0-85007507195

Rights

Mahidol University

Rights Holder(s)

SCOPUS

Bibliographic Citation

Cancer. Vol.123, No.10 (2017), 1791-1799

Suggested Citation

Philippe Rousselot, Stéphane Prost, Joelle Guilhot, Lydia Roy, Gabriel Etienne, Laurence Legros, Aude Charbonnier, Valérie Coiteux, Pascale Cony-Makhoul, Francoise Huguet, Emilie Cayssials, Jean Michel Cayuela, Francis Relouzat, Marc Delord, Heriberto Bruzzoni-Giovanelli, Laure Morisset, François Xavier Mahon, François Guilhot, Philippe Leboulch Pioglitazone together with imatinib in chronic myeloid leukemia: A proof of concept study. Cancer. Vol.123, No.10 (2017), 1791-1799. doi:10.1002/cncr.30490 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/41879

Research Projects

Organizational Units

Authors

Journal Issue

Thesis

Title

Pioglitazone together with imatinib in chronic myeloid leukemia: A proof of concept study

Author(s)

Philippe Rousselot
 Stéphane Prost
 Joelle Guilhot
 Lydia Roy
 Gabriel Etienne
 Laurence Legros
 Aude Charbonnier
 Valérie Coiteux
 Pascale Cony-Makhoul
 Francoise Huguet
 Emilie Cayssials
 Jean Michel Cayuela
 Francis Relouzat
 Marc Delord
 Heriberto Bruzzoni-Giovanelli
 Laure Morisset
 François Xavier Mahon
 François Guilhot
 Philippe Leboulch

Other Contributor(s)

Universite de Versailles Saint-Quentin-en-Yvelines
 CEA Fontenay aux Roses
 Centre Hospitalier Universitaire de Poitiers
 Hôpital Henri Mondor
 Institut Bergonie
 Centre Hospitalier Universitaire de Nice
 Institut Paoli-Calmettes
 Centre Hospitalier Regional Universitaire de Lille
 Centre Hospitalier Annecy Genevois
 Institut Universitaire du Cancer
 Hôpital Saint-Louis
 Universite Paris 7- Denis Diderot
 CHV Centre Hospitalier de Versailles
 Hopital Haut-Lévêque C.H.U de Bordeaux
 Brigham and Women's Hospital and Harvard Medical School
 Mahidol University

Abstract

© 2016 Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. BACKGROUND: We recently reported that peroxisome proliferator-activated receptor γ agonists target chronic myeloid leukemia (CML) quiescent stem cells in vitro by decreasing transcription of STAT5. Here in the ACTIM phase 2 clinical trial, we asked whether pioglitazone add-on therapy to imatinib would impact CML residual disease, as assessed by BCR-ABL1 transcript quantification. METHODS: CML patients were eligible if treated with imatinib for at least 2 years at a stable daily dose, having yielded major molecular response (MMR) but not having achieved molecular response 4.5 (MR4.5) defined by BCR-ABL1/ABL1IS RNA levels ≤ 0.0032%. After inclusion, patients started pioglitazone at a dosage of 30 to 45 mg/day in addition to imatinib. The primary objective was to evaluate the cumulative incidence of patients having progressed from MMR to MR4.5 over 12 months. RESULTS: Twenty-four patients were included (age range, 24-79 years). No pharmacological interaction was observed between the drugs. The main adverse events were weight gain in 12 patients and a mean decrease of 0.4 g/dL in hemoglobin concentration. The cumulative incidence of MR4.5 was 56% (95% confidence interval, 37%-76%) by 12 months, despite a wide range of therapy duration (1.9-15.5 months), and 88% of 17 evaluable patients who were still on imatinib reached MR4.5 by 48 months. The cumulative incidence of MMR to MR4.5 spontaneous conversions over 12 months was estimated to be 23% with imatinib alone in a parallel cohort of patients. CONCLUSION: Pioglitazone in combination with imatinib was well tolerated and yielded a favorable 56% rate. These results provide a proof of concept needing confirmation within a randomized clinical trial (EudraCT 2009-011675-79). Cancer 2017;123:1791–1799. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Keyword(s)

Biochemistry, Genetics and Molecular Biology

Availability

URI

https://repository.li.mahidol.ac.th/handle/20.500.14594/41879

Collections

Scopus 2016-2017