PMID- 30323618
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220321
IS  - 1178-6930 (Print)
IS  - 1178-6930 (Electronic)
IS  - 1178-6930 (Linking)
VI  - 11
DP  - 2018
TI  - Adverse events risk associated with regorafenib in the treatment of advanced 
      solid tumors: meta-analysis of randomized controlled trials.
PG  - 6405-6414
LID - 10.2147/OTT.S156760 [doi]
AB  - BACKGROUND: Regorafenib is a novel multikinase inhibitor (MKI) approved for use 
      in the treatment of metastatic colorectal cancer (CRC), treatment-refractory 
      gastrointestinal stromal tumors, and other solid tumor malignancies. However, the 
      adverse events (AEs) associated with regorafenib have not been systematically 
      investigated. Hence, we performed a meta-analysis to identify AEs associated with 
      regorafenib in patients with advanced solid tumors. METHODS: The databases of 
      PubMed, MEDLINE, and Embase and abstracts presented in American Society of 
      Clinical Oncology annual meetings were searched for relevant publications from 
      January 2004 to September 2017. Eligible studies were limited to prospective 
      randomized controlled trials (RCTs) that evaluate the use of regorafenib in 
      patients with advanced solid tumors. Incidence, relative risk (RR), and 95% CIs 
      were calculated using a random or fixed effects model on the basis of the 
      heterogeneity of the included studies. RESULTS: A total of 2,065 patients from 
      six RCTs were included, and 1,340 of them received regorafenib and 725 received a 
      placebo. Sixteen all-grade AEs and 15 high-grade AEs were investigated for their 
      association with regorafenib. Results showed that hand-foot skin reaction (HFSR; 
      54%), diarrhea (33%), fatigue (32%), hypertension (31%), oral mucositis (28%), 
      and anorexia (23%) were the most frequent clinical AEs. The most common 
      high-grade (grade, >/=3) AEs were HFSR (16%), hypertension (13%), fatigue (6%), 
      increased aspartate aminotransferase (AST; 6%), and hypophosphatemia (6%). Pooled 
      RR showed that the use of regorafenib was associated with an increased risk of 
      developing AEs. Subgroup analysis based on the prior MKI treatment showed that 
      prior MKI treatment was associated with an increased incidence of all-grade 
      anorexia (P=0.03) and a reduced incidence of high-grade increased AST (P=0.04). 
      However, subgroup analysis based on the tumor type showed that no significant 
      differences were found when comparing the RR of all-grade and high-grade AEs in 
      patients with CRC or non-CRC. CONCLUSION: The meta-analysis systematically 
      investigated regorafenib-associated AEs. Knowledge of these AEs is essential for 
      minimizing treatment-related toxicities and improving clinical outcomes.
FAU - Yin, Xiaonan
AU  - Yin X
AD  - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 
      Chengdu 610041, Sichuan, China, hxwcwk@126.com.
FAU - Yin, Yuan
AU  - Yin Y
AD  - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 
      Chengdu 610041, Sichuan, China, hxwcwk@126.com.
FAU - Shen, Chaoyong
AU  - Shen C
AD  - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 
      Chengdu 610041, Sichuan, China, hxwcwk@126.com.
FAU - Chen, Huijiao
AU  - Chen H
AD  - Department of Pathology, West China Hospital, Sichuan University, Chengdu 610041, 
      Sichuan, China.
FAU - Wang, Jiang
AU  - Wang J
AD  - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 
      Chengdu 610041, Sichuan, China, hxwcwk@126.com.
FAU - Cai, Zhaolun
AU  - Cai Z
AD  - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 
      Chengdu 610041, Sichuan, China, hxwcwk@126.com.
FAU - Chen, Zhixin
AU  - Chen Z
AD  - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 
      Chengdu 610041, Sichuan, China, hxwcwk@126.com.
FAU - Zhang, Bo
AU  - Zhang B
AD  - Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, 
      Chengdu 610041, Sichuan, China, hxwcwk@126.com.
LA  - eng
PT  - Journal Article
DEP - 20181002
PL  - New Zealand
TA  - Onco Targets Ther
JT  - OncoTargets and therapy
JID - 101514322
PMC - PMC6174311
OTO - NOTNLM
OT  - AE
OT  - adverse event
OT  - meta-analysis
OT  - multikinase inhibitor
OT  - regorafenib
OT  - safety
COIS- Disclosure The authors report no conflicts of interest in this work.
EDAT- 2018/10/17 06:00
MHDA- 2018/10/17 06:01
PMCR- 2018/10/02
CRDT- 2018/10/17 06:00
PHST- 2018/10/17 06:00 [entrez]
PHST- 2018/10/17 06:00 [pubmed]
PHST- 2018/10/17 06:01 [medline]
PHST- 2018/10/02 00:00 [pmc-release]
AID - ott-11-6405 [pii]
AID - 10.2147/OTT.S156760 [doi]
PST - epublish
SO  - Onco Targets Ther. 2018 Oct 2;11:6405-6414. doi: 10.2147/OTT.S156760. eCollection 
      2018.