PMID- 24629273 OWN - NLM STAT- MEDLINE DCOM- 20140529 LR - 20220310 IS - 1532-1967 (Electronic) IS - 0305-7372 (Linking) VI - 40 IP - 5 DP - 2014 Jun TI - Safety and efficacy of addition of VEGFR and EGFR-family oral small-molecule tyrosine kinase inhibitors to cytotoxic chemotherapy in solid cancers: a systematic review and meta-analysis of randomized controlled trials. PG - 636-47 LID - S0305-7372(14)00024-3 [pii] LID - 10.1016/j.ctrv.2014.02.004 [doi] AB - BACKGROUND: The approach of combining cytotoxic chemotherapy with oral small molecule tyrosine kinase inhibitors (TKIs) has been explored in a large number of randomized trials, in a variety of tumor. We performed a systematic review and meta-analysis to evaluate the safety and efficacy of this therapeutic approach. PATIENTS AND METHODS: PubMed and the ASCO databases were searched up to March 2013. We included randomized trials in which the FDA approved vascular endothelial growth factor receptor (VEGFR) or epidermal growth factor receptor-family (EGFR)-targeted TKI in combination with chemotherapy was compared with chemotherapy alone in patients with any type of solid cancer. The endpoints included safety [fatal adverse events (FAEs), treatment discontinuation, any severe (grade 3 or 4) adverse events (AEs), and individual severe AEs] and efficacy [progression-free survival (PFS), and overall survival (OS)]. The pooled relative risk (RR) or hazard ratio (HR) were calculated. RESULTS: A total of 16,011 patients from 43 trials were included. Compared with chemotherapy alone, the addition of a TKI significantly increased the risk of FAEs (RR, 1.63; 95% CI, 1.32-2.01), treatment discontinuation (RR, 1.80; 95% CI, 1.58-2.06), and any severe AE (RR, 1.25; 95% CI, 1.16-1.36). The addition of a TKI was associated with a significant improvement in PFS (HR, 0.82; 95% CI, 0.76-0.89), but not OS (HR, 0.99; 95% CI, 0.95-1.03). CONCLUSIONS: It is important for physicians to weigh the risk of toxicity versus the modest PFS benefit associated with chemotherapy plus TKI in patients with solid cancers. CI - Copyright (c) 2014 Elsevier Ltd. All rights reserved. FAU - Funakoshi, Tomohiro AU - Funakoshi T AD - Department of Medicine, Beth Israel Medical Center, University Hospital and Manhattan Campus for the Albert Einstein College of Medicine, New York, United States. Electronic address: tfunakoshi@chpnet.org. FAU - Latif, Asma AU - Latif A AD - Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, United States. Electronic address: asma.latif@mountsinai.org. FAU - Galsky, Matthew D AU - Galsky MD AD - Division of Hematology/Oncology, Tisch Cancer Institute, Mount Sinai School of Medicine, New York, United States. Electronic address: matthew.galsky@mssm.edu. LA - eng PT - Comparative Study PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20140224 PL - Netherlands TA - Cancer Treat Rev JT - Cancer treatment reviews JID - 7502030 RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.10.1 (Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor) SB - IM MH - Administration, Oral MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use MH - Clinical Trials, Phase II as Topic MH - Clinical Trials, Phase III as Topic MH - Dose-Response Relationship, Drug MH - Drug-Related Side Effects and Adverse Reactions/epidemiology/*etiology MH - ErbB Receptors/*drug effects/metabolism MH - Female MH - Humans MH - Male MH - Maximum Tolerated Dose MH - Neoplasms/*drug therapy/mortality/pathology MH - Patient Safety MH - Protein Kinase Inhibitors/adverse effects/*therapeutic use MH - Protein-Tyrosine Kinases/antagonists & inhibitors/therapeutic use MH - Randomized Controlled Trials as Topic MH - Receptors, Vascular Endothelial Growth Factor/*drug effects/metabolism MH - Risk Assessment MH - Treatment Outcome OTO - NOTNLM OT - Epidermal growth factor receptor OT - Fatal adverse events OT - Overall survival OT - Progression free survival OT - Severe adverse events OT - Small-molecule tyrosine kinase inhibitor OT - Systematic review and meta-analysis OT - Treatment discontinuation OT - Vascular endothelial growth factor receptor EDAT- 2014/03/19 06:00 MHDA- 2014/05/30 06:00 CRDT- 2014/03/18 06:00 PHST- 2014/01/14 00:00 [received] PHST- 2014/02/09 00:00 [revised] PHST- 2014/02/13 00:00 [accepted] PHST- 2014/03/18 06:00 [entrez] PHST- 2014/03/19 06:00 [pubmed] PHST- 2014/05/30 06:00 [medline] AID - S0305-7372(14)00024-3 [pii] AID - 10.1016/j.ctrv.2014.02.004 [doi] PST - ppublish SO - Cancer Treat Rev. 2014 Jun;40(5):636-47. doi: 10.1016/j.ctrv.2014.02.004. Epub 2014 Feb 24.