PMID- 31169681
OWN - NLM
STAT- MEDLINE
DCOM- 20190613
LR  - 20210110
IS  - 1536-5964 (Electronic)
IS  - 0025-7974 (Print)
IS  - 0025-7974 (Linking)
VI  - 98
IP  - 23
DP  - 2019 Jun
TI  - Safety of combining vascular endothelial growth factor receptor tyrosine-kinase 
      inhibitors with chemotherapy in patients with advanced non-small-cell lung 
      cancer: A PRISMA-compliant meta-analysis.
PG  - e15806
LID - 10.1097/MD.0000000000015806 [doi]
LID - e15806
AB  - BACKGROUND: Vascular endothelial growth factor receptor-tyrosine kinase 
      inhibitors (VEGFR-TKIs) have been developed for targeted therapies in 
      non-small-cell lung cancer (NSCLC); moreover, some drug-related toxic reactions 
      among cancer patients have been reported. A meta-analysis of randomized 
      controlled trials (RCTs) to definite the incidence and the risk of grade >/=3 
      adverse events (AEs), serious and fatal AEs (SAEs and FAEs), with VEGFR-TKIs in 
      advanced/metastatic NSCLC patients was performed. METHODS: A comprehensive 
      literature search was conducted for the clinical trials published up to December 
      2017. Qualified studies allotted patients with advanced/metastatic NSCLC to 
      receive either chemotherapy alone or in combination with VEGFR-TKIs. Data were 
      extracted by 2 authors. RESULTS: Eighteen RCTs of VEGFR-TKIs plus chemotherapy, 
      involving 8461 advanced NSCLC patients were included. The proportion of patients 
      with grade >/=3 AEs was increased with the addition of VEGFR-TKIs (relative risk, 
      1.35; 95% confidence interval [CI] 1.19-1.52; incidence, 68.1% vs 50.1%; 
      P < .001). The most common grade >/=3 AEs was neutropenia (24.9% vs 15.4%, 
      P < .001). Addition of VEGFR-TKIs was also related to the increased risk of SAEs 
      (relative risk, 1.34; 95% CI 1.14-1.56; incidence, 37.8% vs 27.9%; P < .001) and 
      FAEs (relative risk, 2.16, 95% CI 1.47-3.19; incidence, 3.4% vs 1.8%). Subgroup 
      analysis suggested there was no difference in the rates of SAEs and FAEs in the 
      second-line settings. No evidence of bias was found between the literatures. The 
      study was registered with PROSPERO (CRD42018099654). CONCLUSIONS: In comparison 
      with chemotherapy alone, the addition of VEGFR-TKIs in advanced NSCLC patients 
      was related to the increased risk of grades >/=3 AEs, SAEs, and FAEs, especially in 
      the first-line settings. Physicians should be aware of some specific grade >/=3 
      adverse effect, especially haematologic adverse events, and it is also necessary 
      to monitor cancer patients receiving VEGFR-TKIs.
FAU - Lv, Wen-Wen
AU  - Lv WW
AD  - Department of pharmacy, Binzhou Medical University Hospital, Binzhou, People's 
      Republic of China.
FAU - Zhang, Jin-Jie
AU  - Zhang JJ
FAU - Zhou, Xiao-Long
AU  - Zhou XL
FAU - Song, Zheng
AU  - Song Z
FAU - Wei, Chuan-Mei
AU  - Wei CM
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
PL  - United States
TA  - Medicine (Baltimore)
JT  - Medicine
JID - 2985248R
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptors, Vascular Endothelial Growth Factor)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy
MH  - Female
MH  - Humans
MH  - Lung Neoplasms/*drug therapy
MH  - Male
MH  - Middle Aged
MH  - Protein Kinase Inhibitors/*therapeutic use
MH  - Protein-Tyrosine Kinases/*antagonists & inhibitors
MH  - Receptors, Vascular Endothelial Growth Factor/*antagonists & inhibitors
MH  - Treatment Outcome
PMC - PMC6571213
COIS- The authors report no conflicts of interest.
EDAT- 2019/06/07 06:00
MHDA- 2019/06/14 06:00
PMCR- 2019/06/07
CRDT- 2019/06/07 06:00
PHST- 2019/06/07 06:00 [entrez]
PHST- 2019/06/07 06:00 [pubmed]
PHST- 2019/06/14 06:00 [medline]
PHST- 2019/06/07 00:00 [pmc-release]
AID - 00005792-201906070-00015 [pii]
AID - MD-D-19-00654 [pii]
AID - 10.1097/MD.0000000000015806 [doi]
PST - ppublish
SO  - Medicine (Baltimore). 2019 Jun;98(23):e15806. doi: 10.1097/MD.0000000000015806.