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

Autor: Asma Latif, Tomohiro Funakoshi, Matthew D. Galsky
Rok vydání: 2014
Předmět:
Male
Oncology
medicine.medical_specialty
Drug-Related Side Effects and Adverse Reactions
Maximum Tolerated Dose
medicine.medical_treatment
Administration
Oral
Pharmacology
Risk Assessment
law.invention
Clinical Trials
Phase II as Topic
Randomized controlled trial
law
Neoplasms
Internal medicine
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Radiology
Nuclear Medicine and imaging
Progression-free survival
Adverse effect
Protein Kinase Inhibitors
Randomized Controlled Trials as Topic
Chemotherapy
Dose-Response Relationship
Drug
business.industry
Hazard ratio
General Medicine
Protein-Tyrosine Kinases
Discontinuation
ErbB Receptors
Receptors
Vascular Endothelial Growth Factor
Treatment Outcome
Clinical Trials
Phase III as Topic
Meta-analysis
Relative risk
Female
Patient Safety
business
Zdroj: Cancer Treatment Reviews. 40:636-647
ISSN: 0305-7372
DOI: 10.1016/j.ctrv.2014.02.004
Popis: 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.
Databáze: OpenAIRE
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