| Risk of bleeding with vascular endothelial growth factor receptor tyrosine-kinase inhibitors sunitinib and sorafenib: a systematic review and meta-analysis of clinical trials. | |
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MedLine Citation:
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PMID: 19767240 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Youjin Je; Fabio A B Schutz; Toni K Choueiri |
Publication Detail:
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Type: Journal Article; Meta-Analysis; Review Date: 2009-09-18 |
Journal Detail:
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Title: The lancet oncology Volume: 10 ISSN: 1474-5488 ISO Abbreviation: Lancet Oncol. Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-02 Completed Date: 2009-10-22 Revised Date: 2010-02-25 |
Medline Journal Info:
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Nlm Unique ID: 100957246 Medline TA: Lancet Oncol Country: England |
Other Details:
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Languages: eng Pagination: 967-74 Citation Subset: IM |
Affiliation:
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Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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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:
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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:
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Lancet Oncol. 2010 Feb;11(2):112-3; author reply 113
[PMID:
20152763
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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