Common Adverse Reactions Research Articles

Oral Mucositis in Adult Cancer Patients Undergoing Chemotherapy: Six-Month On-Treatment Follow-Up.

Objectives. Oral mucositis (OM) is a common adverse reaction associated with chemotherapy. We conducted a six-month longitudinal study to estimate the cumulative incidence of OM during the first six months of chemotherapy in adult patients with cancer other than head and neck cancer. Secondary objectives were as follows: (a) to scrutinize the oral health status of these patients and its evolution during chemotherapy, as assessed by oral health indices; (b) to estimate adherence to prescribed oral hygiene protocol during chemotherapy; and (c) to analyze ulceration-free survival in these patients. Methods. Sixty-four patients participated. Dental health and oral hygiene were assessed at baseline and at the end. Every month, blood tests were performed and oral lesions were recorded. This study was observational, with the only intervention being instruction in the hygiene protocol. The cumulative incidence of OM was estimated with the patient as the unit of analysis. A repeated measures ANOVA was applied to analyze the monthly blood test results. Ulceration-free survival analysis was conducted with adherence to the oral hygiene protocol as a grouping factor, followed by Cox proportional-hazards regression. Results. The six-month cumulative incidence rate was 43.75%, 95%CI (31.58-56.67%) for OM grade 2 or higher. The hazard ratio of ulceration associated with adherence to the hygiene protocol was 0.154, 95%CI (0.049-0.483), adjusted for age, sex, baseline hygiene index, and class of treatment. Conclusions. Compliance with hygiene recommendations would decrease the OM risk by more than six times, compared to non-compliance.

Platelet-Rich Plasma Injection Combined With Q-Switched Ruby Laser in the Treatment of Periorbital Hyperpigmentation.

Periorbital hyperpigmentation is a prevalent skin condition that represents a large quantity of cases seen in cosmetic dermatology. Patients tend to be left with pigmentation after Q-switched ruby laser treatment, especially the perioribital area. The study is conducted to compare the effect of PRP injection combined with laser therapy versus laser alone for periorbital hyperpigmentation treatment. In this single-center, case-control study, 30 patients with periorbital hyperpigmentation were allocated to receive PRP injection injection after Q-switched ruby laser or Q-switched ruby laser only, followed by a 12-week and 24-week follow-up visit. Visual analogue scale, Sadick tear trough rating scale, and patients' self-evaluation were used to evaluate the therapeutic effect. The combined group achieved a better improvement in long-term effect and had effect on facial rejuvenation. Patient satisfaction was higher in the combined group. Erythema and mild pain were the most common adverse reactions of both groups. Combining with PRP injection can improve the therapeutic effect of Q-switched ruby laser in treating periorbital hyperpigmentation and lessen the risk of post-inflammatory hyperpigmentation, indicating a new option for POH treatment.

The effect of gene polymorphism on ticagrelor metabolism: an in vitro study of 22 CYP3A4 variants in Chinese Han population.

Ticagrelor is a novel oral antiplatelet agent which can selectively inhibit P2Y12 receptor. Bleeding and dyspnea are common adverse reactions of ticagrelor in clinic. The side effects of ticagrelor are correlated with the plasma concentration of ticagrelor. This study aimed to evaluate the catalytic characteristics of 22 CYP3A4 alleles identified in the Chinese Han population on the metabolism of ticagrelor in vitro, focusing on the effect of CYP3A4 polymorphism on ticagrelor metabolism. In this study, insect cells were used to express 22 CYP3A4 variants, which were then incubated with 1-50 µM ticagrelor at 37 °C for 30 minutes to obtain the metabolite (AR-C124910XX). AR-C124910XX was detected by UHPLC-MS/MS to calculate the kinetic parameters, including Km, Vmax and CLint. Compared to the wild-type, most CYP3A4 alleles exhibited significant differences in intrinsic clearance. The intrinsic clearance of CYP3A4*11, *18 and *33 was much higher than that of wild-type; four variants exhibited similar intrinsic clearance values as the wild-type enzyme; The remaining 14 variants showed significantly reduced intrinsic clearance values, ranging from 1.48% to 75.11% of the wild-type; CYP3A4*30 displayed weak or no activity. This study conducted a comprehensive assessment of the effect of CYP3A4 variants on ticagrelor's metabolism. The results suggested that there is allele-specific activity towards ticagrelor in vitro. These findings can provide some insights and predictions for treatment strategies and risk assessments associated with ticagrelor in clinical practice.

Rethinking about Metformin: Promising Potentials.

Metformin is widely used drugs in the treatment of type 2 diabetes mellitus. However, the mechanisms of action are complex and are still not fully understood yet. Metformin has a dose-dependent blood sugar-lowering effect. The most common adverse reactions of metformin are gastrointestinal symptoms, and women tend to be more experienced than men. A positive correlation between the administration of duration and the daily dose of metformin and the risk of vitamin B12 deficiency is confirmed. Novel glucose-lowering mechanism through the activation of AMP-activated protein kinase and alteration of gut microbiota composition is identified. In addition, metformin has immunomodulatory properties in various mechanisms, including anti-inflammatory actions, and so forth. Metformin improves insulin sensitivity, which may reduce the risk of tumor growth in certain cancers. The antiviral effects of metformin may occur through several mechanisms, including blocking angiotensin converting enzyme 2 receptor, and so forth. These potential mechanisms of metformin are promising in various clinical settings, such as inflammatory diseases, autoimmune diseases, cancer, and coronavirus disease 2019.

Simultaneous Confidence Intervals for Signal Detection and Ascertaining Precision of Adverse Event Rates in Clinical Trials

The marketing authorization of a medicinal product is contingent upon demonstration of safety and efficacy in support of the product’s labeled conditions of use. To demonstrate safety, one group of adverse events that requires detailed consideration is common adverse reactions (ARs). ARs and their frequency are reported in prescription drug labeling in the US and EU. The determination of these adverse reactions generally takes a simple approach—usually, inclusion is through the frequency of reporting and whether the adverse event (AE) rate for the drug exceeds the placebo rate. This standard method does not account for confounders or multiplicity. To overcome these limitations, we propose a Monte Carlo approach to detect drug safety signals in clinical trials. We fit regression models incorporating covariates to assess the drug effect on the rate of AEs. Adjustment for multiplicity is carried out through the construction of simultaneous confidence intervals accounting for arbitrary correlations. A computationally efficient multiplier bootstrap approach using the Rademacher sequences is developed to generate random samples from the joint distribution of the estimators for all the AE rates. Compared to Bonferroni-based methods, the proposed method leads to narrower simultaneous confidence intervals and is more powerful in detecting potential safety signals.

A Preliminary Study to Evaluate the Immune Response to a Booster Dose of the Adult Tetanus-Diphtheria Vaccine (Td) Available in Iran

Background: Despite the availability of tetanus-diphtheria (TD) vaccines in Iran, the seroconversion rate of these products as a booster dose is unknown. Objectives: This study evaluates the seroconversion rate of the Iranian Td vaccine in adults who have not been vaccinated in the past decade. Methods: In this study, 20 adult volunteers aged 18 to 60 who had not received the Td vaccine in the past decade received a booster dose of the Iranian Td vaccine. Twenty-eight days after vaccination, the seroconversion rate was evaluated using the ELISA method. Vaccine adverse events were monitored at three time points after vaccination. Results: Seroconversion rates with the Iranian Td vaccine boosters were 75% and 90%, respectively, based on a 4-fold increase in anti-tetanus toxoid antibody titers and a 2- and 4-fold combination. Significant associations were found between the demographic data, specifically female gender and age 43 years and older, with seroconversion rates. Injection-site pain was the most common adverse reaction, with a frequency of 35%. No adverse events were reported between one week and one month after vaccination. Conclusions: Results showed that a booster dose of the Iranian Td vaccine produced a protective titer (> 0.1 IU/mL) and a long-term protective titer (> 1.0 IU/mL) in 100% of participants. The seroconversion rate of the Iranian Td vaccine was comparable to other common tetanus vaccines, including Tenivac®, Adacel®, Infanrix®, Tetavax®, and Vacteta®. The proportion of suitable candidates for plasma donation, based on minimum (2 IU/mL) and maximum (10 IU/mL) anti-tetanus toxoid antibody titers, was 100% and 45%, respectively.

Clinical guidance for cannabidiol-associated hepatotoxicity: A narrative review.

There is increasing evidence that cannabidiol (CBD) use is associated with clinically significant liver enzyme (LE) elevations and drug-induced liver injury (DILI). The proportion of LE elevations and DILI events reported in the literature meet the Council for International Organizations of Medical Sciences' (CIOMS) classification of a common adverse drug reaction. However, these potential adverse events are unknown to many clinicians and may be overlooked. The increasing use of CBD for both medical and non-medical use necessitates clear direction in the diagnosis and management of CBD-associated hepatotoxicity. To our knowledge, no such clinical guidance currently exists. For people presenting with elevated LEs, CBD use should be screened for and be considered in the differential diagnosis. This narrative review will provide clinicians with guidance in the prevention, detection, and management of CBD-related hepatotoxicity.

Mechanisms Underlying the Protective Effects of Obeticholic Acid-Activated FXR in Valproic Acid-Induced Hepatotoxicity via Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations.

Valproic acid (VPA)-induced hepatotoxicity is among the most common and severe adverse drug reactions, limiting its clinical application. Recent studies have suggested that activating the farnesoid X receptor (FXR) could be a promising therapeutic approach to alleviate VPA-induced hepatotoxicity; however, related research remains limited. This study aims to comprehensively investigate the mechanisms underlying FXR activation by obeticholic acid (OCA) for the treatment of VPA-induced hepatotoxicity. Network pharmacology was performed to identify potential targets and pathways underlying the amelioration of VPA-induced hepatotoxicity by OCA. The identified pathways were validated through GEO data analysis, and the affinities between OCA and potential key targets were predicted using molecular docking as well as molecular dynamics simulations. A total of 462 targets associated with VPA-induced hepatotoxicity and 288 targets of OCA were identified, with 81 shared targets. KEGG pathway and GO enrichment analysis indicated that the effect of OCA on VPA-induced hepatotoxicity primarily involved lipid metabolism, as well as oxidative stress and inflammation. The results from GEO data analysis, molecular docking, and molecular dynamics simulations revealed a close association between bile secretion, the PPAR signaling pathway, and the treatment of VPA-induced hepatotoxicity by OCA. Our findings suggest that OCA exhibits potential therapeutic efficacy against VPAinduced hepatotoxicity through multiple targets and pathways, thereby highlighting the therapeutic potential of FXR as a target for treating VPA-induced hepatotoxicity.

Stratified analysis of risk factors affecting vasovagal reactions in first-time whole blood donors: A regional multi-center donor hemovigilance data study

Background and objectivesVasovagal reactions (VVR) are the most common adverse reactions in blood donation. This study aimed to provide and analyze the data of the regional hemovigilance system in Chongqing, China from 2020 to 2022, report the prevalence and explore the risk factors of VVR. Materials and methodsR software (version 4.2.3) was used for all statistical analyses. Frequency and composition rates were used to describe the data of total donation, as well as data on the different types of ADR. The Chi-square test was used to analyze risk factors for VVR and inter-group comparisons of VVR stratified by gender (female/male), age (18–22; 23–29; 30–39; 40–49; 50–60) and season(Spring (Mar.-May.); Summer (Jun.-Aug.); Autumn (sep.-Nov.); Winter (Dec.-Feb.)). ResultsThe reported incidence rate of VVR was 8.69‰ during whole blood donations and 1.02‰ during platelet-apheresis donations.The stratified analysis revealed that female donors aged 18–22 years old and 30–39 years old were reported to have lower VVR rates than male donors, oppositely, higher in females in 50–60 years old. Statistically significant differences in the incidence rate of VVR were observed between winter and summer, and between winter and spring in 18–49 years old. No seasonal variation was found in 50–60 years old. ConclusionsThe reported incidence rate of VVR related to blood donation was very low and varied from those calculated by other haemovigilance systems. The higher prevalence of VVR in young, first-time donors, college students, donating in mobile vehicles, males and in spring. Among first-time donors, the prevalence of VVR was higher in males than in females; and stratified analysis revealed there were seasonal variation and gender differences within a same age group.

Feasibility and Safety of PD-1 Blockades Among Elderly Patients with Metastatic Esophageal Squamous Cell Carcinoma: A Real-World Study.

This study aimed to identify the effectiveness and safety of PD-1 blockades among elderly patients with metastatic esophageal squamous cell carcinoma (ESCC) clinically. A total of 78 elderly patients with previously treated metastatic ESCC aged ≥65 years who received PD-1 blockades monotherapy were included retrospectively. Demographic characteristics, therapeutic effectiveness and adverse reactions of the elderly patients who underwent PD-1 blockade therapy were recorded. Regular follow-up was conducted for all patients. The analysis aimed to identify potential risk factors for OS by examining the correlation between prognosis and subgroups based on baseline characteristics. The median age of the 78 elderly patients was 73 years, ranging from 65 to 87 years. Among the 78 patients, 18 cases showed partial response, 26 cases had stable disease, 29 cases experienced progressive disease and 5 cases were not assessable for response, yielding an ORR of 23.1%, a DCR of 56.4%. The prognostic outcomes indicated that among the 78 patients with metastatic ESCC who received PD-1 blockades, the median PFS was 3.1 months [95% confidence interval (CI): 1.64-4.56], and the median OS was 10.9 months (95% CI: 6.02-15.78), 24-month OS rate was 22.7% (95% CI: 12.8-34.2%). In terms of the safety profile, among the 78 patients with metastatic ESCC during PD-1 blockades single-agent treatment, a total of 61 patients (78.2%) experienced any grade adverse reactions and the incidence of grade ≥3 adverse reactions were 20.5%. Briefly, the common adverse reactions manifested as fatigue (32.1%), gastrointestinal reaction (24.4%), diarrhea (19.2%), anemia (17.9%) and rash (16.7%). Overall tolerability of PD-1 blockade monotherapy in elderly patients with metastatic ESCC was acceptable and manageable. PD-1 blockades single agent demonstrated encouraging effectiveness and acceptable safety profile for elderly patients with previously treated metastatic ESCC in clinical practice. Prospective study should be performed to elucidate the conclusion in this study subsequently.

Current status of rabies vaccination in humans in Cao Bang province, Vietnam during 2018 – 2022

A cross - sectional study conducted in Cao Bang Province during 2018 to 2022, aimed to describe the status of rabies vaccination during that period. Cao Bang was recorded 11179 case exposure to rabies. The results showed that a total of 22,080 rabies vaccinations were administered, with 53.8% of the recipients being men and 46.2% being women. The most common age group taken post-exposure prophylaxis against rabies was 25 - 49 years old, accounted for 34.6% of the vaccinations. Dogs were the primary source of rabies transmission to humans. Of the animal involved, 72.0% of it remained in normal health condition. Leg bites were the most common occurrence, made up 58.1% and grade II wounds comprised 60.5% of the cases. Interestingly, 94.4% of patients sought early preventive treatment within 10 days of exposure. The rate of patients experiencing local reactions after vaccination was 3.64%, while 4.85% had systemic reactions. The majority of adverse reactions caused by post-exposure prophylaxis was pain (3.44%), while the most common systemic adverse reaction was fever (3.17%). Through the above information, we make recommendations for rabies prevention in Cao Bang province such as raising people’s awareness, especially for men, for children, management and paying attention to animals (confine, chain, vaccination, monitoring, etc.,) and when people at risk of exposure to rabies virus they need to go to medical centers as soon as possible for prophylaxis treatment and explaining adverse reactions after rabies vaccination is necessary to make people feel more secure.

FDA Approval Summary: Repotrectinib for Locally Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer.

On November 15, 2023, the U.S. Food and Drug Administration (FDA) granted traditional approval to repotrectinib (Augtyro, Bristol Myers Squibb Corporation) for the treatment of adult patients with locally advanced or metastatic receptor tyrosine kinase encoded by the ROS1 gene (ROS1)-positive non-small cell lung cancer (NSCLC). The approval was based on TRIDENT-1, a single-arm trial with multiple cohorts of patients with ROS1 fusion-positive (hereafter "ROS1-positive") NSCLC (NCT03093116), who were either treatment naïve or had received prior ROS1 tyrosine kinase inhibitor (TKI) and/or platinum-based chemotherapy. The primary efficacy outcome measure is objective response rate (ORR) assessed by blinded independent central review (BICR) using response evaluation criteria in solid tumors version 1.1. ORR was assessed in 71 patients who were ROS1 TKI naïve and 56 patients who had received a prior ROS1 TKI. Among the 71 patients who were ROS1 TKI naïve, the ORR was 79% (95% CI, 68-88), median duration of response was 34.1 months (95% CI, 26-NE). In patients who had received a prior ROS1 TKI and no prior chemotherapy, the ORR was 38% (95% CI, 25-52). The median duration of response was 14.8 months (95% CI, 7.6-NE); BICR-assessed responses were observed in CNS metastases in patients in both cohorts and in patients who developed resistance mutations following prior TKI therapy. The most common (>20%) adverse reactions were dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, ataxia, fatigue, cognitive disorders, and muscular weakness. A unique feature of this ROS1 TKI approval is the inclusion of robust evidence of efficacy in patients with ROS1-positive NSCLC who had progressed on prior ROS1 TKIs.

The efficacy and safety of avapritinib in the treatment of molecular biologically positive core binding factor-acute myeloid leukemia with KIT mutation after allogeneic hematopoietic stem cell transplantation

Objective: To investigate the efficacy and safety of avapritinib in the treatment of molecular biologically positive core binding factor-acute myeloid leukemia (CBF-AML) with KIT mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: We retrospectively analyzed the clinical data of six patients with molecular biologically positive CBF-AML with KIT mutation after allo-HSCT, who were treated with avapritinib at Henan Cancer Hospital from December 2021 to March 2023, and evaluated the efficacy and safety of avapritinib. Results: After 1 month of treatment with avapritinib, the transcription level of the fusion gene decreased in six patients, and the transcription level decreased by ≥1 log in five patients. In four patients who received avapritinib for ≥3 months, the fusion gene turned negative, and the median time to turn negative was 2.0 (range: 1.0-3.0) months. Up to the end of follow-up, four patients had no recurrence. The most common adverse reaction of avapritinib was myelosuppression, including neutropenia in two cases, thrombocytopenia in two cases, and anemia in one case. The non-hematological adverse reactions were nausea in two cases, edema in one case, and memory loss in one case, all of which were grades 1-2. Conclusion: Avapritinib was effective for molecular biologically positive CBF-AML patients with KIT mutation after allo-HSCT. The main adverse reaction was myelosuppression, which could generally be tolerated.

Effectiveness of surgery combined with photodynamic therapy for recurrent respiratory papillomatosis

ObjectiveThis study aims to analyze the safety and effectiveness of a new model of surgery combined with Photodynamic therapy for treating Recurrent Respiratory Papillomatosis (RRP). MethodsReview the case data of patients with RRP who opted for comprehensive surgery combined with Photodynamic therapy at the Nanjing BenQ Medical Center, from January 2021 to May 2023. The efficacy of this program was evaluated by comparing the annual number of surgeries and Derkay scores before and after the surgery. ResultsA total of 23 RRP patients were included in the study. After treatment, the recurrence rate was 65.2 % (15/23), with an average recurrence time of 94.3 ± 50.8 days. The average Derkay score at the time of recurrence was significantly lower than the average pre-treatment Derkay score (P < 0.001). The average annual recurrence rate before treatment was 2.2 ± 1.3, compared to 1.5 ± 1.5 after treatment, with no significant difference (P = 0.16). However, subgroup analysis revealed a significant decrease in the annual recurrence rate of adult-onset RRP after treatment (P = 0.01). The most common adverse reaction was mild pharyngeal pain (11/23). There were 3 cases of new-onset vocal cord adhesions. No patients experienced serious respiratory-related adverse reactions, anesthesia-related adverse reactions, or systemic phototoxic reactions. ConclusionIn conclusion, this study indicates that surgery combined with Photodynamic therapy (PDT) might be a safe and effective option for treating RRP, especially in patients with Adult-Onset Recurrent Respiratory Papillomatosis (AORRP).

Effect of ensifentrine on dyspnea in patients with moderate-to-severe chronic obstructive pulmonary disease: pooled analysis of the ENHANCE trials

ABSTRACT Background Dyspnea is a critical component of chronic obstructive pulmonary disease (COPD). We report the effect of ensifentrine, a novel PDE3/PDE4 inhibitor, on dyspnea using pooled data from the Phase 3 ENHANCE-1/2 trials. Methods The pooled population (ensifentrine, n = 975; placebo, n = 574) included patients aged 40–80 years with post-bronchodilator FEV1/FVC <0.7, FEV1 30–70% predicted, mMRC Dyspnea Scale score ≥2, and a smoking history ≥10 pack-years. Patients taking dual LAMA/LABA or LAMA/LABA/ICS triple therapy were excluded. Dyspnea measures included the Transition Dyspnea Index (TDI), Evaluating Respiratory Symptoms (E-RS), and rescue medication use. Results After 24 weeks, ensifentrine significantly improved TDI scores (least-squares mean difference, 0.97; 95% CI, 0.64, 1.30; p < 0.001) and across all TDI subdomains. Ensifentrine-treated patients were more likely to be TDI responders at week 24 (p < 0.001), which was consistent across clinically relevant subgroups. Ensifentrine-treated patients had improved E-RS breathlessness subdomain scores (p = 0.053) and reduced rescue medication use (p = 0.002). Conclusion Ensifentrine produced clinically meaningful improvements in multiple dyspnea measures in patients with symptomatic, moderate-to-severe COPD. A limitation of this study was the exclusion of patients taking dual LAMA/LABA and LAMA/LABA/ICS triple therapy. Clinical trial registration www.clinicaltrials.gov identifiers are ENHANCE-1: NCT04535986; ENHANCE-2: NCT04542057.

FDA Approval Summary: Asciminib for Ph+ CML in Chronic Phase Treated with Two or More Tyrosine Kinase Inhibitors and for the T315I Mutation.

On October 29, 2021, FDA granted accelerated approval to asciminib (SCEMBLIX; Novartis), a tyrosine kinase inhibitor (TKI), for the treatment of adult patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more TKIs, and granted traditional approval to asciminib for adult patients with Ph+ CML in CP with the T315I mutation. The first indication was approved based on major molecular response (MMR) at 24 weeks in the ASCEMBL study, a randomized trial comparing asciminib with bosutinib in patients who had failed two or more TKIs. This indication was ultimately granted traditional approval on October 12, 2022, based on safety data and MMR rate at 96 weeks of 38% [95% confidence interval (CI), 30-46] in the asciminib arm versus 16% (95% CI, 8-26) in the bosutinib arm (P value: 0.001). The second indication was approved based on MMR rate by 96 weeks of 49% (95% CI, 34-64) in the single-arm CABL001X2101 study. The most common (≥20%) adverse reactions included upper respiratory tract infections, musculoskeletal pain, headache, fatigue, nausea, rash, and diarrhea. The most common (≥20%) laboratory abnormalities were thrombocytopenia, neutropenia, anemia, lymphopenia, hypertriglyceridemia, hyperuricemia, and increases in creatine kinase, alanine aminotransferase, aspartate aminotransferase, lipase, and amylase. This manuscript describes the basis for approval of these indications.

A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer.

Mecapegfilgrastim, a long-actinggranulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or thefluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial.

This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

The efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant recurrent ovarian cancer

Objectives: To investigate the efficacy and safety of anlotinib combined with niraparib in treating patients with platinum-resistant ovarian cancer. Methods: Thirty-five patients with pathological confirmed platinum-resistant ovarian cancer who experienced progression after receiving at least two lines of standard treatment were eligible. All of them were treated with anlotinib combined with niraparib between September 2019 and October 2021. The primary endpoint was progression-free survival (PFS). The second endpoints included overall survival, objective response rate (ORR), disease control rate (DCR) and safety. Survival analysis was performed using the Kaplan-Meier method and Log-rank test, and influence factor analysis was performed using Cox proportional risk regression models. Results: The best overall response showed that partial response was observed in 14 patients, stable disease was noted within 13 patients, and progressive disease was found in 8 patients. Therefore, the ORR and DCR of these 35 patients were 40.0% (95% CI:22.9%-57.1%) and 77.1% (95% CI:62.9%-91.4%), respectively. The median follow-up duration was 18.9 months (6.9-32.2). The median PFS was 6.5 months (95% CI:5.35-7.66). Multivariate Cox regression analysis for PFS indicated that age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, International Federation of Gynecology and Obstetrics (FIGO) stage, and BRCA mutation status were independent factors influencing PFS (P＜0.05). Additionally, the PFS in patients with BRCA mutation who have never received PARP inhibitor treatment was significantly longer than that in patients without BRCA mutation who have been exposed to prior PARPi treatment (15.0 vs 6.0 month, P=0.029). The most common treatment-related adverse reactions were fatigue (85.7%), hematologic toxic (85.7%) and hypertension (74.3%). There were no treatment-related deaths. Conclusion: Anlotinib combined with niraparib shows a promising efficacy and tolerable safety in platinum-resistant ROC patients.

Brexpiprazole for Agitation Associated With Dementia Due to Alzheimer's Disease

Alzheimer's disease (AD) is a prevalent neurodegenerative disease characterized by progressive cognitive and functional decline. Nearly all patients with AD develop neuropsychiatric symptoms (NPSs). Agitation is one of the most distressing and challenging NPS. Brexpiprazole is an oral antipsychotic and is the first approved pharmacologic agent in the United States for the treatment of agitation associated with dementia due to AD. Its effect is thought to be from its partial serotonin 5-HT1A and dopamine D2 receptor agonist activity and serotonin 5-HT2A receptor antagonism. Brexpiprazole is a maintenance medication, and it should not be used “as needed” or as a “PRN” treatment for breakthrough agitation. Brexpiprazole is a major substrate of CYP2D6 and CYP3A4. Dose adjustments may be required for drug interactions or impaired renal or hepatic function. Clinical trials found brexpiprazole 2 to 3 mg/d demonstrated significant improvements in agitation, with brexpiprazole showing an approximate 5-point greater reduction on change in the Cohen-Mansfield Agitation Inventory total score at week 12 from baseline compared with placebo. Brexpiprazole is generally well tolerated and safe, and common adverse reactions when used for this indication include dizziness, headaches, insomnia, nasopharyngitis, somnolence, and urinary tract infections. Like other antipsychotics used for agitation in AD, brexpiprazole is associated with higher mortality rates compared with placebo. In a long-term care setting, there are several considerations for its use. Benefits include an oral agent that is well tolerated and clinical data showing statistically significant effects on agitation. However, brexpiprazole has not been studied in head-to-head clinical trials against other antipsychotics, and there are differing opinions if the agitation score reductions translate to a clinically meaningful difference. The approval of brexpiprazole signals favorably for upcoming agents for this indication, including escitalopram and dextromethorphan-bupropion. Both escitalopram and dextromethorphan-bupropion are currently undergoing clinical trials.