Risk factors associated with palbociclib-induced neutropenia in patients with metastatic breast cancer.

BACKGROUND: Neutropenia is the most common adverse event with palbociclib, an oral cyclin-dependent kinase 4/6 inhibitor, with grade 3/4 neutropenia occurring in up to 67% of patients in phase III trials evaluating this agent in metastatic breast cancer. This retrospective chart review assessed characteristics of patients on palbociclib to evaluate for risk factors in the development of grade 3/4 neutropenia. PATIENTS AND METHODS: Patients with metastatic breast cancer who received palbociclib were included. Patient demographics collected included age, gender, race, body mass index, breast cancer treatment history, palbociclib starting dose, baseline absolute neutrophil count, baseline platelet count, concomitant hormonal therapy, concomitant use of denosumab, and use of concomitant strong CYP3A4 inhibitors/inducers. Events of interest occurring within 30 days of initiation of palbociclib were also noted including antibiotic and corticosteroid use, mucosal conditions, open wounds, or surgery. The incidence and potential risk factors for grade 3/4 neutropenia in the first 6 months of treatment were analyzed. RESULTS: A total of 257 patients were included in the analysis with 206 patients (80.2%) and 139 patients (54.1%) experiencing all-grade neutropenia and grade 3/4 neutropenia, respectively. Multivariate analysis found baseline myelosuppression and recent antibiotic use to be independent predictors of grade 3/4 neutropenia. Normal weight patients had an increased risk for grade 3/4 neutropenia compared to obese patients by multivariate analysis. CONCLUSION: The results of this study showed baseline myelosuppression and recent antibiotic use within 30 days of palbociclib initiation were predictive of a higher incidence of grade 3/4 neutropenia. Obese patients were less likely to develop grade 3/4 neutropenia compared to normal weight patients.

Impact of time in therapeutic range after left ventricular assist device placement: a comparison between thrombus and thrombus-free periods.

The association between time in therapeutic range (TTR) and clinical outcomes in patients with left ventricular assist devices (LVADs) on chronic warfarin therapy is not well understood. This study assessed TTR using the Rosendaal Method prior to suspected or confirmed pump thrombosis or ischemic stroke. Each patient served as their own control. Characteristics and TTR in 1, 2, and 3 months prior to thrombus (thrombus period) were compared to a thrombus-free period during 6 months to 3 months prior to thrombus (control period). There were 30 thrombus events observed in 25 patients for a rate of 0.06 events per LVAD day. Average TTR (target INR = 2-3) over 3 months for patients combined in both the thrombus and control time period was 53.4%. TTR (target INR = 2-3) was 11.4% lower 1 month prior to thrombus than the comparable month in the control period (p = 0.029). The TTR (target INR = 1.8-2.5) was 11.8% lower in the thrombus time period compared to the control time period 2 months prior to thrombus (p = 0.032). Our study found an increased risk of thrombosis with lower TTR in months leading up to thrombus compared to a thrombus-free period.

Affective and behavioral dysfunction under antiepileptic drugs in epilepsy: Development of a new drug-sensitive screening tool.

OBJECTIVE: Behavioral problems and psychiatric symptoms are common in patients with epilepsy and have a multifactorial origin, including adverse effects of antiepileptic drugs (AEDs). In order to develop a screening tool for behavioral AED effects, the aim of this study was to identify behavioral problems and symptoms particularly sensitive to AED drug load and the presence/absence of AEDs with known negative psychotropic profiles. METHODS: Four hundred ninety-four patients with epilepsy were evaluated who had been assessed with three self-report questionnaires on mood, personality, and behavior (Beck Depression Inventory, BDI; Neurological Disorders Depression Inventory for Epilepsy extended, NDDI-E; and Fragebogen zur Persönlichkeit bei zerebralen Erkrankungen, FPZ). Drug-sensitive items were determined via correlation analyses and entered into an exploratory factor analysis for scale construction. The resulting scales were then analyzed as a function of drug treatment. RESULTS: Analyses revealed 30 items, which could be allocated to six behavioral domains: Emotional Lability, Depression, Aggression/Irritability, Psychosis & Suicidality, Risk- & Sensation-seeking, and Somatization. Subsequent analysis showed significant effects of the number of AEDs on behavior, as in Emotional Lability (F=2.54, p=.029), Aggression/Irritability (F=2.29, p=.046), Psychosis & Suicidality (F=2.98, p=.012), and Somatization (F=2.39, p=.038). Affective and behavioral difficulties were more prominent in those patients taking AEDs with supposedly negative psychotropic profiles. These effects were largely domain-unspecific and primarily manifested in polytherapy. CONCLUSION: Drug-sensitive behavioral domains and items were identified which qualify for a self-report screening tool. The tool indicates impairments with a higher drug load and when administering AEDs with negative psychotropic profiles. The next steps require normalization in healthy subjects and the clinical validation of the newly developed screening tool PsyTrack along with antiepileptic drug treatment.