PMID- 27443985
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1752-8062 (Electronic)
IS  - 1752-8054 (Print)
IS  - 1752-8054 (Linking)
VI  - 9
IP  - 5
DP  - 2016 Oct
TI  - Patient-Level Adverse Event Patterns in a Single-Institution Study of the 
      Multi-Kinase Inhibitor Sorafenib.
PG  - 260-266
LID - 10.1111/cts.12408 [doi]
AB  - Novel characterization of patterns of adverse events (AEs) of kinase inhibitors 
      (KIs) could reveal new insights on human molecular physiology and methods to 
      improve the therapeutic index of KIs. Incidence and severity of AEs for each of 
      157 patients enrolled in sorafenib clinical trials were determined for three 
      clinically relevant treatment intervals: weeks 0-3, weeks 3-7, and after 7 weeks. 
      The most common within patient co-occurrences were mucositis with dermatologic 
      events: hand-foot syndrome (HFS; odds ratio [OR] = 4.36; p = 0.0017) and rash (OR 
      = 5.32; p < 0.001). Prevalence of severe: alopecia (p = 0.02), diarrhea (p < 
      0.001), and fatigue (p = 0.005) increased over the course of therapy. Incidence 
      of HFS (60%) and diarrhea (25%) increased up to a minimum steady-state 
      concentration (approximately 5 mcg mL(-1) ) and plateaued thereafter. Common AEs 
      of sorafenib occur in distinct temporal and tissue distribution patterns and this 
      analysis identified unrecognized relationships among mechanism-dependent and 
      independent effects of a KI.
CI  - (c) 2016 The Authors. Clinical and Translational Science published by Wiley 
      Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and 
      Therapeutics.
FAU - Karovic, S
AU  - Karovic S
AD  - Section of Hematology/Oncology, Department of Medicine, University of Chicago, 
      Chicago, Illinois, USA.
FAU - Shiuan, E F
AU  - Shiuan EF
AD  - Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, 
      Illinois, USA.
FAU - Zhang, S Q
AU  - Zhang SQ
AD  - Section of Hematology/Oncology, Department of Medicine, University of Chicago, 
      Chicago, Illinois, USA.
FAU - Cao, H
AU  - Cao H
AD  - Department of Health Studies, University of Chicago, Chicago, Illinois, USA.
FAU - Maitland, M L
AU  - Maitland ML
AD  - Section of Hematology/Oncology, Department of Medicine, University of Chicago, 
      Chicago, Illinois, USA.
AD  - Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, 
      Chicago, Illinois, USA.
AD  - Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA.
LA  - eng
PT  - Journal Article
DEP - 20160721
PL  - United States
TA  - Clin Transl Sci
JT  - Clinical and translational science
JID - 101474067
PMC - PMC5350995
EDAT- 2016/07/23 06:00
MHDA- 2016/07/23 06:01
PMCR- 2016/10/01
CRDT- 2016/07/23 06:00
PHST- 2015/10/28 00:00 [received]
PHST- 2016/05/27 00:00 [accepted]
PHST- 2016/07/23 06:00 [pubmed]
PHST- 2016/07/23 06:01 [medline]
PHST- 2016/07/23 06:00 [entrez]
PHST- 2016/10/01 00:00 [pmc-release]
AID - CTS12408 [pii]
AID - 10.1111/cts.12408 [doi]
PST - ppublish
SO  - Clin Transl Sci. 2016 Oct;9(5):260-266. doi: 10.1111/cts.12408. Epub 2016 Jul 21.