PMID- 32684988
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220415
IS  - 1758-8340 (Print)
IS  - 1758-8359 (Electronic)
IS  - 1758-8340 (Linking)
VI  - 12
DP  - 2020
TI  - Dose reduction and discontinuation of standard-dose regorafenib associated with 
      adverse drug events in cancer patients: a systematic review and meta-analysis.
PG  - 1758835920936932
LID - 10.1177/1758835920936932 [doi]
LID - 1758835920936932
AB  - BACKGROUND: Regorafenib (REG) is an oral multikinase inhibitor used in colorectal 
      cancer, gastrointestinal stromal tumour and hepatocellular carcinoma. Several 
      adverse events (AEs) are commonly reported during REG administration, and 
      strategies for managing AEs in everyday clinical practice include supportive 
      care, dose modifications and, when necessary, treatment withdrawal. We performed 
      a systematic review and meta-analysis to assess the schedule treatment 
      modifications of REG associated with AEs across randomized controlled clinical 
      trials (RCTs). METHODS: Eligible studies included RCTs assessing standard dose 
      REG versus placebo. Outcomes of interest included: AE-related permanent 
      discontinuation, dose interruptions and dose reductions. RESULTS: We retrieved 
      all the relevant RCTs through PubMed/Med, Cochrane library and EMBASE: 7 eligible 
      studies involving a total of 2099 patients (Regorafenib: 1362; placebo: 737) were 
      included in our analysis. The use of REG was associated with higher incidence and 
      risk of all outcomes of interest when compared with placebo. The incidences of 
      permanent discontinuation, dose interruptions and dose reductions in patients 
      receiving REG were 9.7%, 57.2% and 47%, respectively, versus 3.3%, 16.7% and 7.7% 
      of placebo group; compared with placebo, the summary relative risks (RRs) of 
      permanent discontinuation, dose interruptions and dose reductions in REG arm were 
      2.80 (95% CI 1.85-4.22), 3.21 (95% CI 2.59-3.99) and 6.02 (95% CI 3.28-11.03), 
      respectively. CONCLUSIONS: Treatment with REG at the standard dose of 160 mg is 
      associated with a significant increase in AE-related permanent discontinuation, 
      dose interruptions and dose reductions. Prompt identification and management of 
      AEs seem mandatory to obtain maximal benefit from REG treatment. In the current 
      landscape, dose personalization of REG may have the potential to improve quality 
      of life, minimize treatment discontinuation and maximize patient outcomes.
CI  - (c) The Author(s), 2020.
FAU - Rizzo, Alessandro
AU  - Rizzo A
AUID- ORCID: 0000-0002-5257-8678
AD  - Department of Specialized, Experimental and Diagnostic Medicine, 
      Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
FAU - Nannini, Margherita
AU  - Nannini M
AD  - Medical Oncology Unit, Sant'Orsola-Malpighi University Hospital, via Massarenti 
      9, Bologna, 40138, Italy.
FAU - Novelli, Marco
AU  - Novelli M
AD  - Department of Statistical Sciences, University of Bologna, Bologna, Italy.
FAU - Dalia Ricci, Angela
AU  - Dalia Ricci A
AD  - Department of Specialized, Experimental and Diagnostic Medicine, 
      Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
FAU - Scioscio, Valerio Di
AU  - Scioscio VD
AD  - Department of Statistical Sciences, University of Bologna, Bologna, Italy.
FAU - Pantaleo, Maria Abbondanza
AU  - Pantaleo MA
AD  - Department of Specialized, Experimental and Diagnostic Medicine, 
      Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
LA  - eng
PT  - Journal Article
DEP - 20200707
PL  - England
TA  - Ther Adv Med Oncol
JT  - Therapeutic advances in medical oncology
JID - 101510808
PMC - PMC7343359
OTO - NOTNLM
OT  - GIST
OT  - colorectal cancer
OT  - gastrointestinal stromal tumours
OT  - meta-analysis
OT  - regorafenib
COIS- Conflict of interest statement: The authors declare that there is no conflict of 
      interest.
EDAT- 2020/07/21 06:00
MHDA- 2020/07/21 06:01
PMCR- 2020/07/07
CRDT- 2020/07/21 06:00
PHST- 2020/02/01 00:00 [received]
PHST- 2020/05/22 00:00 [accepted]
PHST- 2020/07/21 06:00 [entrez]
PHST- 2020/07/21 06:00 [pubmed]
PHST- 2020/07/21 06:01 [medline]
PHST- 2020/07/07 00:00 [pmc-release]
AID - 10.1177_1758835920936932 [pii]
AID - 10.1177/1758835920936932 [doi]
PST - epublish
SO  - Ther Adv Med Oncol. 2020 Jul 7;12:1758835920936932. doi: 
      10.1177/1758835920936932. eCollection 2020.