PMID- 25580915
OWN - NLM
STAT- MEDLINE
DCOM- 20150601
LR  - 20220114
IS  - 1096-8652 (Electronic)
IS  - 0361-8609 (Linking)
VI  - 90
IP  - 4
DP  - 2015 Apr
TI  - Cardiovascular and pulmonary adverse events in patients treated with BCR-ABL 
      inhibitors: Data from the FDA Adverse Event Reporting System.
PG  - E66-72
LID - 10.1002/ajh.23938 [doi]
AB  - Rare but serious cardiovascular and pulmonary adverse events (AEs) have been 
      reported in patients with chronic myeloid leukemia treated with BCR-ABL 
      inhibitors. Clinical trial data may not reflect the full AE profile of BCR-ABL 
      inhibitors because of stringent study entry criteria, relatively small sample 
      size, and limited duration of follow-up. To determine the utility of the FDA AE 
      Reporting System (FAERS) surveillance database for identifying AEs possibly 
      associated with the BCR-ABL inhibitors imatinib, dasatinib, and nilotinib in the 
      postmarketing patient population, we conducted Multi-Item Gamma Poisson Shrinker 
      disproportionality analyses of FAERS reports on AEs in relevant system organ 
      classes. Signals consistent with the known safety profiles of these agents as 
      well as signals for less well-described AEs were detected. Bone marrow necrosis, 
      conjunctival hemorrhage, and peritoneal fluid retention events were uniquely 
      associated with imatinib. AEs that most commonly reached the threshold for 
      dasatinib consisted of terms relating to hemorrhage and fluid retention, 
      including pleural effusion and pericardial effusion. Most terms that reached the 
      threshold solely with nilotinib were related to peripheral and cardiac vascular 
      events. Although this type of analysis cannot determine AE incidence or establish 
      causality, these findings elucidate the AEs reported in patients treated with 
      BCR-ABL inhibitors across multiple clinical trials and in the community setting 
      for all approved and nonapproved indications, suggesting drug-AE associations 
      warrant further investigation. These findings emphasize the need to consider 
      patient comorbidities when selecting amongst BCR-ABL inhibitors.
CI  - (c) 2015 Wiley Periodicals, Inc.
FAU - Cortes, Jorge
AU  - Cortes J
AD  - Department of Leukemia, Division of Cancer Medicine, University of Texas MD 
      Anderson Cancer Center, Houston, Texas.
FAU - Mauro, Michael
AU  - Mauro M
FAU - Steegmann, Juan Luis
AU  - Steegmann JL
FAU - Saglio, Giuseppe
AU  - Saglio G
FAU - Malhotra, Rachpal
AU  - Malhotra R
FAU - Ukropec, Jon A
AU  - Ukropec JA
FAU - Wallis, Nicola T
AU  - Wallis NT
LA  - eng
GR  - P01 CA049639/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150130
PL  - United States
TA  - Am J Hematol
JT  - American journal of hematology
JID - 7610369
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Pyrimidines)
RN  - 0 (Thiazoles)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.2 (Fusion Proteins, bcr-abl)
RN  - F41401512X (nilotinib)
RN  - RBZ1571X5H (Dasatinib)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Adverse Drug Reaction Reporting Systems
MH  - Aged
MH  - Antineoplastic Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Benzamides/administration & dosage/adverse effects/therapeutic use
MH  - Cardiovascular Diseases/*chemically induced/epidemiology
MH  - Dasatinib
MH  - Databases, Factual
MH  - Fusion Proteins, bcr-abl/*antagonists & inhibitors
MH  - Humans
MH  - Imatinib Mesylate
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*drug therapy/metabolism
MH  - Logistic Models
MH  - Lung Diseases/*chemically induced/epidemiology
MH  - Middle Aged
MH  - Piperazines/administration & dosage/adverse effects/therapeutic use
MH  - Product Surveillance, Postmarketing
MH  - Pyrimidines/administration & dosage/adverse effects/therapeutic use
MH  - Thiazoles/administration & dosage/adverse effects/therapeutic use
MH  - United States
MH  - United States Food and Drug Administration
MH  - Young Adult
EDAT- 2015/01/13 06:00
MHDA- 2015/06/02 06:00
CRDT- 2015/01/13 06:00
PHST- 2014/12/19 00:00 [received]
PHST- 2014/12/29 00:00 [revised]
PHST- 2015/01/03 00:00 [accepted]
PHST- 2015/01/13 06:00 [entrez]
PHST- 2015/01/13 06:00 [pubmed]
PHST- 2015/06/02 06:00 [medline]
AID - 10.1002/ajh.23938 [doi]
PST - ppublish
SO  - Am J Hematol. 2015 Apr;90(4):E66-72. doi: 10.1002/ajh.23938. Epub 2015 Jan 30.