PMID- 26371140
OWN - NLM
STAT- MEDLINE
DCOM- 20160404
LR  - 20220114
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Print)
IS  - 0732-183X (Linking)
VI  - 33
IP  - 35
DP  - 2015 Dec 10
TI  - Tyrosine Kinase Inhibitor-Associated Cardiovascular Toxicity in Chronic Myeloid 
      Leukemia.
PG  - 4210-8
LID - 10.1200/JCO.2015.62.4718 [doi]
AB  - For most patients with chronic myeloid leukemia, tyrosine kinase inhibitors 
      (TKIs) have turned a fatal disease into a manageable chronic condition. Imatinib, 
      the first BCR-ABL1 TKI granted regulatory approval, has been surpassed in terms 
      of molecular responses by the second-generation TKIs nilotinib, dasatinib, and 
      bosutinib. Recently, ponatinib was approved as the only TKI with activity against 
      the T315I mutation. Although all TKIs are associated with nonhematologic adverse 
      events (AEs), experience with imatinib suggested that toxicities are typically 
      manageable and apparent early during drug development. Recent reports of 
      cardiovascular AEs with nilotinib and particularly ponatinib and of pulmonary 
      arterial hypertension with dasatinib have raised concerns about long-term 
      sequelae of drugs that may be administered for decades. Here, we review what is 
      currently known about the cardiovascular toxicities of BCR-ABL1 TKIs, discuss 
      potential mechanisms underlying cardiovascular AEs, and elucidate discrepancies 
      between the reporting of such AEs between oncology and cardiovascular trials. 
      Whenever possible, we provide practical recommendations, but we concede that 
      cause-directed interventions will require better mechanistic understanding. We 
      suggest that chronic myeloid leukemia heralds a fundamental shift in oncology 
      toward effective but mostly noncurative long-term therapies. Realizing the full 
      potential of these treatments will require a proactive rational approach to 
      minimize long-term cardiovascular and cardiometabolic toxicities.
CI  - (c) 2015 by American Society of Clinical Oncology.
FAU - Moslehi, Javid J
AU  - Moslehi JJ
AD  - Javid J. Moslehi, Vanderbilt-Ingram Cancer Center and Vanderbilt University 
      School of Medicine, Nashville, TN; and Michael Deininger, University of Utah 
      Huntsman Cancer Institute, Salt Lake City, UT.
FAU - Deininger, Michael
AU  - Deininger M
AD  - Javid J. Moslehi, Vanderbilt-Ingram Cancer Center and Vanderbilt University 
      School of Medicine, Nashville, TN; and Michael Deininger, University of Utah 
      Huntsman Cancer Institute, Salt Lake City, UT. michael.deininger@hci.utah.edu.
LA  - eng
GR  - R01CA178397-01A1/CA/NCI NIH HHS/United States
GR  - P01CA049639/CA/NCI NIH HHS/United States
GR  - P30CA042014/CA/NCI NIH HHS/United States
GR  - R01 CA178397/CA/NCI NIH HHS/United States
GR  - K08HL09703/HL/NHLBI NIH HHS/United States
GR  - P01 CA049639/CA/NCI NIH HHS/United States
GR  - P30 CA042014/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20150914
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Aniline Compounds)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Imidazoles)
RN  - 0 (Nitriles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyridazines)
RN  - 0 (Pyrimidines)
RN  - 0 (Quinolines)
RN  - 4340891KFS (ponatinib)
RN  - 5018V4AEZ0 (bosutinib)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - F41401512X (nilotinib)
RN  - RBZ1571X5H (Dasatinib)
SB  - IM
MH  - Aniline Compounds/adverse effects
MH  - Antineoplastic Agents/administration & dosage/*adverse effects
MH  - Cardiovascular System/*drug effects
MH  - Clinical Trials as Topic
MH  - Dasatinib/adverse effects
MH  - Fusion Proteins, bcr-abl/*antagonists & inhibitors
MH  - Humans
MH  - Hypertension/chemically induced
MH  - Imatinib Mesylate/adverse effects
MH  - Imidazoles/adverse effects
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy
MH  - Molecular Targeted Therapy
MH  - Nitriles/adverse effects
MH  - Protein Kinase Inhibitors/administration & dosage/*adverse effects
MH  - Pyridazines/adverse effects
MH  - Pyrimidines/adverse effects
MH  - Quinolines/adverse effects
PMC - PMC4658454
COIS- Authors' disclosures of potential conflicts of interest are found in the article 
      online at www.jco.org. Author contributions are found at the end of this article.
EDAT- 2015/09/16 06:00
MHDA- 2016/04/05 06:00
PMCR- 2016/12/10
CRDT- 2015/09/16 06:00
PHST- 2015/09/16 06:00 [entrez]
PHST- 2015/09/16 06:00 [pubmed]
PHST- 2016/04/05 06:00 [medline]
PHST- 2016/12/10 00:00 [pmc-release]
AID - JCO.2015.62.4718 [pii]
AID - R4718 [pii]
AID - 10.1200/JCO.2015.62.4718 [doi]
PST - ppublish
SO  - J Clin Oncol. 2015 Dec 10;33(35):4210-8. doi: 10.1200/JCO.2015.62.4718. Epub 2015 
      Sep 14.