Dataset Information

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.

SUBMITTER: Karovic S

PROVIDER: S-EPMC5350995 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Patient-Level Adverse Event Patterns in a Single-Institution Study of the Multi-Kinase Inhibitor Sorafenib.

Karovic S S Shiuan E F EF Zhang S Q SQ Cao H H Maitland M L ML

Clinical and translational science 20160721 5

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 syndrom ...[more]

PMID: 27443985

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Project description:BackgroundOver the last decade attention has grown to give patients and next of kin (P/N) more substantial roles in adverse event investigations. Adverse event investigations occur after adverse events that resulted in death or severe injury. Few studies have focused on patient perspectives on their involvement in such investigations. The present study sets out to investigate how P/N and patient representatives (client councils and the Patient Federation Netherlands) view the involvement of P/N in adverse event investigations, particularly whether and why they want to involved, and how they want to shape their involvement.MethodsThe study features qualitative data on three levels: interviews with P/N (personal), focus groups with representatives of client councils (institutional), and an interview with the Patient Federation Netherlands (national). Researchers used inductive, thematic analysis and validated the results through data source triangulation.ResultsThe initiative taken by the hospitals in this study provided P/N with the space to feel heard and a position as legitimate stakeholder. P/N appreciated the opportunity to choose whether and how they wanted to be involved in the investigation as stakeholders. P/N emphasized the need for hospitals to learn from the investigations, but for them the investigation was also part of a more encompassing relationship. P/N's views showed the inextricable link between the first conversation with the health care professional and the investigation, and the ongoing care after the investigation was finalized. Hence, an adverse event investigation is part of a broader experience when understood from a patient perspective.ConclusionsAn adverse event investigation should be considered as part of an existing relationship between P/N and hospital that starts before the investigation and continues during follow up care. It is crucial for hospitals to take the initiative in the investigation and in the involvement of P/N. P/N motivations for involvement can be understood as driven by agency or communion. Agentic motivations include being an active participant by choice, while communion motivations include the need to be heard.

Project description:Background and Objective Immune checkpoint inhibitor (ICI)-associated myocarditis is a fatal immune-related adverse events (irAEs), which is prone to affecting multiple organ systems. Multi-organ irAEs have not been fully studied in ICI-associated myocarditis. Therefore, we aimed to explore the impact of multi-organ irAEs on ICI myocarditis in terms of clinical features, treatment, and prognosis. Methods This was a retrospective study. The clinical data of ICI myocarditis patients were collected from 6 hospitals in China. The risk factors and characteristics of pure myocarditis and multi-organ irAEs were analyzed. The overall survival (OS) after myocarditis was analyzed and univariate and multivariate regression analysis were performed. Results A total of 46 patients were analyzed in this study. Multi-organ irAEs were common (30/46, 65.2%) and prone to severe heart failure. The severe myocarditis was observed in 32 patients (69.6%). When myocarditis occurred, neutrophil to lymphocyte ratio, C-reactive protein, lactate dehydrogenase, interleukin (IL)-6, IL-10, creatine kinase, MB isoenzyme of creatine kinase, and brain natriuretic peptide increased from baseline, but absolute lymphocyte count decreased. Thymoma (B2/B3) was a risk factor for multi-organ irAEs. Heart failure and myocarditis were more severe in patients with multi-organ irAEs and require early corticosteroid therapy (<24 hours). Univariate analysis showed that age ≥ 60 years, myocarditis (grade 3-4), heart failure (grade 3-4), multi-organ irAEs, and severe myocarditis were associated with OS after myocarditis. After adjusting for other factors, heart failure (grade 3-4) was an independent risk factor for immune-related myocarditis (HR: 6.655, 95% CI: 1.539-28.770, p=0.011). Conclusion Patients with ICI-associated myocarditis had multi-organ irAEs with a high incidence of severe myocarditis, mortality, and poor prognosis. Thymoma was prone to those patients with multiple organs involvement. Patients could benefit from early corticosteroid intervention. Heart failure (grade 3-4) was an independent risk factor for OS after myocarditis.

Dataset Information

Patient-Level Adverse Event Patterns in a Single-Institution Study of the Multi-Kinase Inhibitor Sorafenib.

Publications

Patient-Level Adverse Event Patterns in a Single-Institution Study of the Multi-Kinase Inhibitor Sorafenib.

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