Combination of pioglitazone with tyrosine kinase inhibitor - CML - Chronic myeloid leukemia
Important notice: You must inform your CML doctor or a qualified doctor before using this drug. The material presented here is for information purposes only; it is not a substitute for your physician’s guidance and care. The side-effects of pioglitazone would also to be taken into account if this treatment were to be offered in routine care.
" Philippe Leboulch, M.D., a professor of medicine and cell biology at the University of Paris, and colleagues temporarily administered pioglitazone in addition to imatinib to three patients with chronic myeloid leukemia.
Here we show that the residual CML LSC pool can be gradually purged by the glitazones, antidiabetic drugs that are agonists of peroxisome proliferator-activated receptor-γ (PPARγ). We found that activation of PPARγ by the glitazones decreases expression of STAT5 and its downstream targets HIF2α5 and CITED26, which are key guardians of the quiescence and stemness of CML LSCs.
When pioglitazone was given temporarily to three CML patients in chronic residual disease in spite of continuous treatment with imatinib, all of them achieved sustained CMR, up to 4.7 years after withdrawal of pioglitazone. This suggests that clinically relevant cancer eradication may become a generally attainable goal by combination therapy that erodes the cancer stem cell pool."
Extract of Prost S, Relouzat F, Spentchian M, et al. Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists. Nature. 2015. doi:10.1038/nature15248
" Philippe Leboulch, M.D., a professor of medicine and cell biology at the University of Paris, and colleagues temporarily administered pioglitazone in addition to imatinib to three patients with chronic myeloid leukemia.
Here we show that the residual CML LSC pool can be gradually purged by the glitazones, antidiabetic drugs that are agonists of peroxisome proliferator-activated receptor-γ (PPARγ). We found that activation of PPARγ by the glitazones decreases expression of STAT5 and its downstream targets HIF2α5 and CITED26, which are key guardians of the quiescence and stemness of CML LSCs.
When pioglitazone was given temporarily to three CML patients in chronic residual disease in spite of continuous treatment with imatinib, all of them achieved sustained CMR, up to 4.7 years after withdrawal of pioglitazone. This suggests that clinically relevant cancer eradication may become a generally attainable goal by combination therapy that erodes the cancer stem cell pool."
Extract of Prost S, Relouzat F, Spentchian M, et al. Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists. Nature. 2015. doi:10.1038/nature15248
VIDEOS
What Are the Side Effects of Actos (Pioglitazone)?
Pioglitazone
Pioglitazone to Prevent Vascular Events - IRIS Study Reviewed
May 12, 2016, iForumRx
What Are the Side Effects of Actos (Pioglitazone)?
Pioglitazone
Pioglitazone to Prevent Vascular Events - IRIS Study Reviewed
May 12, 2016, iForumRx
CLINICAL TRIALS
Therapies in Combination or Sequentially With Tyrosine Kinase Inhibitors (TKIs) in Chronic Phase Chronic Myelogenous Leukemia Patients in CCR (ACTIW) (ACTIW)
CML ACTIM (European Leukemia Trial Registry)
Safety and Efficiency Study of Pioglitazone in Combination With Imatinib Mesylate to Treat Chronic Myelogenous Leukemia (SESPI)
Pioglitazone and Tyrosine Kinase Inhibitor in Treating Patients With Relapsed Chronic Myeloid Leukemia
Second STOP After Pioglitazone Priming in CML Patients (PIO2STOP)
The prospective pioglitazone clinical trial in macrovascular events (PROactive): can pioglitazone reduce cardiovascular events in diabetes? Study design and baseline characteristics of 5238 patients.
Cohort Study of Pioglitazone and Bladder Cancer in Patients With Type II Diabètes
Efficacy of Pioglitazone and Insulin in Treating Subjects With Type 2 Diabetes Mellitus and Renal Failure
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ARTICLES
Pilot Study of Imatinib Discontinuation in Patients with Chronic Myeloid Leukemia with Deep Molecular Response (EDI-PIO) – Evaluation of Pioglitazone in Treatment-Free Remission
December 2017, ASH2017
Pioglitazone Prevents Stroke in Patients with a Recent TIA or Ischemic Stroke: A Planned Secondary Analysis of the IRIS Trial
October 30, 2017, Circulation
Pioglitazone And Metformin (Precautions) WARNING
March 1, 2017, Mayo Clinic
Pioglitazone Plus Imatinib Leads to Molecular Response in Patients With Chronic-Phase Chronic Myeloid Leukemia
January 25, 2017, ASH clinicals news
Adding Pioglitazone Could Improve Molecular Response in CML Patients
Janvier 6, 2017, Cancer Network
Adding Pioglitazone to Imatinib May Improve Response Rate in CML
January 4, 2017, Cancer Therapy Advisor
Pioglitazone together with imatinib in chronic myeloid leukemia: A proof of concept study *********
December 27, 2016, Cancer
PPAR GAMMA Agonist in combination with BCR/ABL TKI in patients of CML-CP with suboptimal molecular response
December 20, 2016, Annals of Oncology
Pioglitazone, Other TZDs May Add Benefit to TKI Therapy in CML
January 11, 2016, Cancer Network
PPARγ ligands increase antileukemic activity of second- and third-generation tyrosine kinase inhibitors in chronic myeloid leukemia cells
January 8, 2016, Blood Cancer journal
Teaching an Old Dog New Tricks: Eradication of Leukemia Stem Cells
December 2015, The hematologist
PPARγ: Welcoming the New Kid on the CML Stem Cell Block.
October 12, 2015, PublMed
Pioglitazone purges quiescent CML stem cells
September 17, 2015, Nature
Adding pioglitazone to imatinib may improve treatment of chronic myeloid leukemia
September 9, 2015, Oncology Nurse Advisor
Adding Glitazone to Chemotherapy May Help Treat Chronic Myeloid Leukemia
September 3, 2015, Cancer Therapy Advisor
Diabetes drug may help in leukaemia
September 3, 2015, BBC News
Erosion of the chronic myeloid leukaemia stem cell pool by PPARγ agonists
September 2, 2015, Journal Nature
Could Common Diabetes Drugs Help Fight Leukemia?
September 2, 2015, HealthDay
Could Common Diabetes Drugs Help Fight Leukemia?
September 2, 2015, WebMD
Co-operating STAT5 and AKT signaling pathways in chronic myeloid leukemia and mastocytosis: possible new targets of therapy
March 2014, Heamatologica
Targeting STAT5 Expression Resulted in Molecular Response Improvement in Patients with Chronic Phase CML Treated with Imatinib
2012, Journal Blood
The use of pioglitazone and the risk of bladder cancer in people with type 2 diabetes: nested case-control study
April 18, 2012, thebmj
Pioglitazone inhibits the growth of human leukemia cell lines and primary leukemia cells while sparing normal hematopoietic stem cells
August 29, 2006, PubMed
Treating type 2 diabetes in renal insufficiency: the role of pioglitazone
October 2003, PubMed
See also Dr. Philippe Rousselot
