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Background: Appropriate adverse event (AE) management and maintenance of therapeutic intensity are necessary to achieve therapeutic benefits of CDK4/6 inhibitors (palbociclib and abemaciclib) in hormone receptor-positive, HER2-negative metastatic/recurrent breast cancer. Objective: This study was aimed at clarifying the effect of AEs associated with palbociclib and abemaciclib on treatment. Methods: A total of 62 and 49 patients were prescribed palbociclib and abemaciclib, respectively, at our hospital from January 1, 2018 to June 30, 2023. The rate and reasons for treatment discontinuation, interruption of administration, and changes in dose and dosing schedule, treatment duration, and relative dose intensity (RDI) were compared between the groups of patients prescribed the 2 treatments. Results: Treatment discontinuation due to AEs occurred more frequently with abemaciclib (12 patients) because of interstitial lung disease and hepatic and renal events than with palbociclib (5 patients; P =.008). Administration was interrupted in 57 (91.9%) and 35 (71.4%) patients treated with palbociclib and abemaciclib, respectively (P =.004). Dose reduction occurred in 37 (67.3%) and 19 (47.5%) patients treated with palbociclib and abemaciclib, respectively (P =.053). The median [range] treatment duration was 301 [21-1643] days for palbociclib and 238 [70-1526] days for abemaciclib (log-rank test, P =.581). The median RDI was 59.7% and 59.6% for palbociclib and abemaciclib, respectively (P =.539). Although the AEs of palbociclib and abemaciclib affected the treatment considerably, the treatment duration and RDI were similar. Conclusion: CDK4/6 inhibitors should be selected based on the tolerability and manageability of each AE. [ABSTRACT FROM AUTHOR]

Introduction: Anaplastic lymphoma kinase (ALK) has been to be involved in the uptake and regulation of dopamine 2 receptor (D2R), a G protein-coupled receptor expressed in various brain regions. Therefore, it is crucial to understand the relationship between ALK inhibitors and seizures is an important issue. This study investigated the relationship between ALK inhibitors and seizures. Methods: This study investigated the relationship between ALK inhibitors and seizures through a disproportionality analysis using the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). The target drugs were the ALK inhibitors crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib. The seizures covered were defined high-level group term (HLGT): "Seizures (incl. subtype)" including high-level term (HLT): "seizures and seizure disorders NEC." This study used the information component (IC), a signal score, as a Bayesian statistical method for disproportionality analysis. The signal detection criteria used in this study were the same as those reported previously: a lower limit of 95% credible interval (CrI) for IC >0. Results: The signal scores of '"seizures and seizure disorders not elsewhere classified (NEC)" "for each ALK inhibitor were crizotinib (IC: −0.00052, 95% CrI: −0.38–0.27), ceritinib (IC: 1.18, 95% CrI: 0.68–1.54), alectinib (IC: 0.68, 95% CrI: 0.19–1.02), brigatinib (IC: 1.04, 95% CrI: 0.32–1.54), and lorlatinib (IC: 0.82, 95% CrI: 0.11–1.32). On the other hand, "generalized tonic-clonic seizures," "partial simple seizures NEC," "absence seizures," and "partial complex seizures" had no or few reported cases, and no signal was detected. Conclusion: To our knowledge, this is the first report to evaluate the relationship between ALK inhibitors and seizures using post-marketing surveillance data. These results suggest that ceritinib, alectinib, brigatinib, and lorlatinib, which are highly brain-migrating drugs, are associated with seizures. [ABSTRACT FROM AUTHOR]

Parkinson's disease affects millions of people worldwide, and without significant progress in disease prevention and treatment, its incidence and prevalence could increase by more than 30% by 2030. Researchers have focused on targeting sleep and the circadian system as a novel treatment strategy for Parkinson's disease. This study investigated the association between melatonin receptor agonists and Parkinson's disease, using the Food and Drug Administration (FDA) Adverse Events Reporting System (FAERS). The target drugs were melatonin receptor agonists including ramelteon, tasimelteon, and agomelatine. Parkinson's disease cases were defined according to the Medical Dictionary for Regulatory Activities (MedDRA) 25.0; Standardized MedDRA Query (SMQ) using both the "narrow" and "broad" preferred terms (PTs) associated with Parkinson's disease. The association between melatonin receptor agonists (ramelteon, tasimelteon, and agomelatine) and Parkinson's disease was evaluated by the reporting odds ratio. Upon analyzing the data from all patients registered in the FAERS, ramelteon (ROR: 0.66, 95% confidence interval [95% CI]: 0.51–0.84) and tasimelteon (ROR: 0.49, 95% CI: 0.38–0.62) showed negative correlations with Parkinson's disease. Conversely, only agomelatine was positively correlated with Parkinson's disease (ROR: 2.63, 95% CI: 2.04–3.40). These results suggest that among the melatonin receptor agonists, ramelteon and tasimelteon are negatively correlated with Parkinson's disease. In contrast, agomelatine was shown to be positively correlated with Parkinson's disease. These results should be used in research to develop drugs for the treatment of Parkinson's disease, fully considering the limitations of the spontaneous reporting system. [ABSTRACT FROM AUTHOR]

This article explores the connection between the duration of action of benzodiazepine hypnotic drugs and blepharospasm, a type of eye muscle spasm. The study analyzed reports from the FDA Adverse Events Reporting System and found that benzodiazepine drugs had a higher number of reports and signal scores for blepharospasm compared to other hypnotic drugs. The study suggests that ultrashort-acting and short-acting benzodiazepines may be associated with drug-induced blepharospasms. It also notes that the incidence of blepharospasm was higher in females. However, the study acknowledges that the data used is based on spontaneous reports and further research is needed for stronger evidence. [Extracted from the article]

Introduction: We aimed to compare the safety of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma (HCC) in patients with Child-Pugh A (CP-A) and Child-Pugh B (CP-B) and to determine the adverse events (AEs) that cause dose reduction/interruption of treatment in patients with CP-B. Methods: Sixty-six patients with lenvatinib as a first-line treatment for HCC at Ogaki Municipal Hospital (Ogaki, Japan) between April 2018 and January 2022 were retrospectively evaluated. We analyzed the treatment duration, AEs, and reasons for dose reduction/interruption associated with lenvatinib treatment in patients with CP-A and CP-B HCC. Results: The CP-B group had significantly more cases of grade ≥ 2 fatigue and anorexia than the CP-A group (p = 0.045 and p = 0.042, respectively). Regarding AEs that caused dose reduction/interruption of treatment, the CP-A group had significantly more cases of proteinuria than the CP-B group (p = 0.015), whereas the CP-B group had significantly more cases of hand-foot syndrome (HFS) than the CP-A group (p = 0.013). Conclusion: Patients with CP-B have greater difficulty than patients with CP-A in continuing treatment with repeated dose reductions/interruption of treatment due to intolerable grade ≥ 2 AEs (fatigue and anorexia). HFS is more likely to cause dose reduction/interruption of treatment in CP-B than in CP-A unresectable HCC. [ABSTRACT FROM AUTHOR]

The letter to the editor discusses a study on drugs associated with epidermal necrolysis in children. The authors of the letter point out some issues with the statistical analysis used in the study and suggest alternative methods for detecting signals specific to the pediatric population. They recommend using relative reported odds ratio (ROR) and information component delta (ICΔ) to reduce false positive signals. The authors conclude by stating that using these alternative methods would lead to a better hypothesis that more readers would accept. [Extracted from the article]

Chemotherapy has helped prolong survival in patients with malignant lymphoma, enhancing their quality of life (QOL). Despite the eventual decline in the QOL of patients, the impact of initial chemotherapy remains poorly understood. A prospective patient-reported QOL survey among patients with malignant lymphoma receiving initial chemotherapy was conducted, targeting those treated at Gifu Municipal Hospital (Gifu, Japan) between January 2021 and December 2022. Surveys were conducted pre- and post-chemotherapy based on the EuroQol 5 dimensions. Drug costs were calculated using official prices and analyzed from the cost payer's perspective via cost-utility analysis. Among the 60 patients included in the present study, 28 had diffuse large B-cell lymphoma. Cyclophosphamide, doxorubicin, vincristine, prednisolone ± rituximab therapy was the most common treatment (38 patients) and demonstrated superior cost-effectiveness due to its lowest cost and change in utility value. Initial chemotherapy for patients with malignant lymphoma generally improved the QOL. Clinical trial registration: UMIN000042868 (registered on December 28, 2020). [ABSTRACT FROM AUTHOR]