title: Patient-Level Adverse Event Patterns in a Single-Institution Study of the Multi-Kinase Inhibitor Sorafenib.
abstract: 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.
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
authors.forename: S
authors.initials: S
authors.lastname: Karovic
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Chicago, Chicago, Illinois, USA.
authors.forename: E F
authors.initials: EF
authors.lastname: Shiuan
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.
authors.forename: S Q
authors.initials: SQ
authors.lastname: Zhang
authors.affiliation: Department of Health Studies, University of Chicago, Chicago, Illinois, USA.
authors.forename: H
authors.initials: H
authors.lastname: Cao
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, Illinois, USA.|Committee on Clinical Pharmacology and Pharmacogenomics, University of Chicago, Chicago, Illinois, USA.|Comprehensive Cancer Center, University of Chicago, Chicago, Illinois, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Maitland