PMID- 24930624
OWN - NLM
STAT- MEDLINE
DCOM- 20140826
LR  - 20220309
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 50
IP  - 12
DP  - 2014 Aug
TI  - Cardiovascular events among 1090 cancer patients treated with sunitinib, 
      interferon, or placebo: a comprehensive adjudicated database analysis 
      demonstrating clinically meaningful reversibility of cardiac events.
PG  - 2162-70
LID - S0959-8049(14)00681-9 [pii]
LID - 10.1016/j.ejca.2014.05.013 [doi]
AB  - PURPOSE: To define cardiovascular (CV) risk and reversibility of cardiac events 
      in patients who received sunitinib versus comparator treatment (interferon-alfa 
      or placebo). PATIENTS AND METHODS: We performed a retrospective adjudication of 
      comprehensive CV adverse events (AEs) from two phase 3 trials. Components of the 
      comprehensive CV AE end-point comprised hypertension, symptomatic and 
      asymptomatic left ventricular ejection fraction decreases (SD-LVEF; AD-LVEF) and 
      extent of reversibility, heart-failure symptoms, thromboembolic events, 
      dysrhythmia and CV death. Three cardiologists and one oncologist, blinded to 
      treatment allocation, adjudicated suspected CV AEs in the pooled trial database 
      (N=1090). RESULTS: Incidence rates (IR) for sunitinib versus Interferon-alfa 
      (IFN-alpha)/placebo were hypertension: 6.9 versus 2.6 (hazard ratio (HR), 3.1; 95% 
      confidence interval (CI), 2.4-4.0); SD-LVEF: 0.4 versus 0.2 (HR, 2.5; 95% CI, 
      1.0-6.2); AD-LVEF: 1.1 versus 0.8 (HR, 2.1; 95% CI, 1.3-3.4); and composite CV AE 
      end-point: 10.1 versus 4.8 (HR, 2.5; 95% CI, 2.0-3.1), however reversibility, not 
      previously quantified, was found to be clinically meaningful. CONCLUSIONS: 
      Hypertension and SD-LVEF/AD-LVEF were significantly higher with sunitinib versus 
      IFN-alpha/placebo. Among patients who experienced a cardiac event, symptomatic and 
      asymptomatic instances of decreased cardiac dysfunction were adjudicated as 
      reversible in 47 of 83 (56%) and 17 of 30 (57%), respectively. Among 
      sunitinib-treated patients, many were able to resume sunitinib dosing following 
      resolution of events, a finding that is important for clinical care. In 
      comparator groups, symptomatic and asymptomatic instances were adjudicated as 
      reversible in 4 of 6 (66.7%) and 11 of 21 (52%), respectively. Thromboembolic, 
      dysrhythmic and/or CV deaths were not significantly higher in sunitinib-treated 
      patients.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Ewer, Michael S
AU  - Ewer MS
AD  - The University of Texas MD Anderson Cancer Center, Houston, TX, United States. 
      Electronic address: mewer@mdanderson.org.
FAU - Suter, Thomas M
AU  - Suter TM
AD  - Bern University Hospital, Bern, Switzerland.
FAU - Lenihan, Daniel J
AU  - Lenihan DJ
AD  - Vanderbilt Heart and Vascular Institute, Nashville, TN, United States.
FAU - Niculescu, Liviu
AU  - Niculescu L
AD  - Pfizer Oncology, New York, NY, United States.
FAU - Breazna, Aurora
AU  - Breazna A
AD  - Pfizer Oncology, New York, NY, United States.
FAU - Demetri, George D
AU  - Demetri GD
AD  - Ludwig Center at Harvard, Dana-Farber Cancer Institute Sarcoma Center, and 
      Harvard Medical School, Boston, MA, United States.
FAU - Motzer, Robert J
AU  - Motzer RJ
AD  - Memorial Sloan-Kettering Cancer Center, New York, NY, United States.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140612
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Indoles)
RN  - 0 (Interferon-alpha)
RN  - 0 (Pyrroles)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Angiogenesis Inhibitors/*adverse effects
MH  - Antineoplastic Agents/*adverse effects
MH  - Cardiovascular Diseases/*chemically induced/epidemiology
MH  - Clinical Trials, Phase III as Topic
MH  - Humans
MH  - Hypertension/chemically induced/epidemiology
MH  - Incidence
MH  - Indoles/*adverse effects
MH  - Interferon-alpha/*adverse effects
MH  - Kaplan-Meier Estimate
MH  - Middle Aged
MH  - Neoplasms/complications/*drug therapy
MH  - Pyrroles/*adverse effects
MH  - Randomized Controlled Trials as Topic
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Sunitinib
OTO - NOTNLM
OT  - Cancer treatment-related hypertension
OT  - Cardiotoxicity
OT  - Reversibility of cardiotoxic events
OT  - Sunitinib
EDAT- 2014/06/17 06:00
MHDA- 2014/08/27 06:00
CRDT- 2014/06/17 06:00
PHST- 2014/03/06 00:00 [received]
PHST- 2014/04/30 00:00 [revised]
PHST- 2014/05/05 00:00 [accepted]
PHST- 2014/06/17 06:00 [entrez]
PHST- 2014/06/17 06:00 [pubmed]
PHST- 2014/08/27 06:00 [medline]
AID - S0959-8049(14)00681-9 [pii]
AID - 10.1016/j.ejca.2014.05.013 [doi]
PST - ppublish
SO  - Eur J Cancer. 2014 Aug;50(12):2162-70. doi: 10.1016/j.ejca.2014.05.013. Epub 2014 
      Jun 12.