Document Detail


Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials.
MedLine Citation:
PMID:  19767240     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Sunitinib and sorafenib are oral vascular endothelial growth factor receptor (VEGFR) tyrosine-kinase inhibitors used in various cancers. Bleeding has been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to calculate the incidence and relative risk associated with use of sunitinib and sorafenib. METHODS: We searched PubMed (from January, 1966, to April, 2009) and meeting proceedings of the American Society of Clinical Oncology and the European Society of Medical Oncology (2004-09) for relevant clinical trials. Eligible studies included phase 2 and 3 trials and expanded-access programmes. Statistical analyses were done to calculate summary incidences, relative risks, and 95% CI, using random-effects or fixed-effects models based on the heterogeneity of included studies. FINDINGS: 23 trials were selected for the meta-analysis, yielding a total of 6779 patients. The incidence of bleeding events (all grades) was 16.7% (95% CI 12.7-21.5), and that of high-grade events was 2.4% (1.6-3.9). The relative risk of all-grade bleeding events associated with sunitinib and sorafenib (for randomised controlled trials only) was 2.0 (1.14-3.49; p=0.015). Our analysis was also stratified by underlying malignant disease (renal-cell carcinoma vs non-renal-cell carcinoma) and agent used, but no differences were recorded. INTERPRETATION: Treatment with the VEGFR tyrosine-kinase inhibitors sunitinib and sorafenib is associated with a significant increase in risk of bleeding. FUNDING: None.
Authors:
Youjin Je; Fabio A B Schutz; Toni K Choueiri
Publication Detail:
Type:  Journal Article; Meta-Analysis; Review     Date:  2009-09-18
Journal Detail:
Title:  The lancet oncology     Volume:  10     ISSN:  1474-5488     ISO Abbreviation:  Lancet Oncol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-02     Completed Date:  2009-10-22     Revised Date:  2010-02-25    
Medline Journal Info:
Nlm Unique ID:  100957246     Medline TA:  Lancet Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  967-74     Citation Subset:  IM    
Affiliation:
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / adverse effects*
Benzenesulfonates / adverse effects*
Clinical Trials as Topic
Hemorrhage / chemically induced*,  epidemiology*
Humans
Incidence
Indoles / adverse effects*
Pyridines / adverse effects*
Pyrroles / adverse effects*
Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors*
Risk Assessment
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Benzenesulfonates; 0/Indoles; 0/Pyridines; 0/Pyrroles; 0/sorafenib; 0/sunitinib; EC 2.7.10.1/Receptors, Vascular Endothelial Growth Factor
Comments/Corrections
Comment In:
Lancet Oncol. 2010 Feb;11(2):112-3; author reply 113   [PMID:  20152763 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Extended lymphadenectomy versus conventional surgery for rectal cancer: a meta-analysis.
Next Document:  The role of Doppler and placental screening.