Dexamethasone-sparing on days 2-4 with combined palonosetron, neurokinin-1 receptor antagonist, and olanzapine in cisplatin: a randomized phase III trial (SPARED Trial).

BACKGROUND: This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy. METHODS: Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%. RESULTS: A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life. CONCLUSION: DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation. CLINICAL TRIALS REGISTRY NUMBER: UMIN000032269.

Impact of body weight-based dosing of palonosetron and ondansetron on postoperative nausea and vomiting following laparoscopic sleeve gastrectomy: a randomized, double-blind study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a frequent adverse effect following laparoscopic sleeve gastrectomy. Palonosetron with a standard dosing (75 µg) schedule has been questioned due to its low efficiency in obese patients. This study aimed to investigate the effectiveness and safety of the body weight-based dosing of palonosetron in managing PONV following laparoscopic sleeve gastrectomy. METHODS: A single-center, prospective, double-blinded randomized study was conducted between August 2021 and December 2021. Patients who underwent laparoscopic sleeve gastrectomy were prospectively recruited in the study. One hundred patients were randomly divided into palonosetron (Group P) and ondansetron (Group O). The demographic and clinical variables were recorded. The primary outcome of the study was the incidence of PONV between the two groups during the hospitalization. The secondary outcomes were the number of rescue anti-emetic and analgesic medications and the Functional Living Index-Emesis scores. RESULTS: There were 50 patients in each group (Group P and Group O). There were significant differences in the scores of POVN, nausea, and vomiting favoring Group P. In Group P, the rate of patients using rescue anti-emetics was significantly lower. The incidence of complete response and proportion of patients with higher Functional Living Index-Emesis scores were significantly higher in patients using palonosetron. CONCLUSIONS: The use of palonosetron significantly reduced the incidence of PONV following laparoscopic sleeve gastrectomy. There was a significant improvement in the scores of Functional Living Index-Emesis in patients using palonosetron.

[Safety of umeclidinium/vilanterol in Chinese patients in a real-world setting: a prospective, multicenter, single-arm, observational study].

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

Effectiveness of Palonosetron, 1-Day Dexamethasone, and Aprepitant in Patients Undergoing Carboplatin-Based Chemotherapy.

INTRODUCTION: Dexamethasone (DEX)-sparing strategy with 5-hydroxytryptamine-3 receptor antagonist (5HT3RA) and aprepitant (APR), as triplet antiemetic prophylaxis, is associated with poor control of delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving carboplatin (CBDCA)-based chemotherapy. This study aimed to evaluate whether using palonosetron (PALO) as a 5HT3RA provides superior control with CINV than first-generation (1st) 5HT3RA in triplet antiemetic prophylaxis with a DEX-sparing strategy. METHODS: Pooled patient-level data from a nationwide, multicenter, and prospective observational study were analyzed to compare the incidence of CINV between patients administered PALO and 1st 5HT3RA in combination with 1-day DEX and APR. RESULTS: No significant differences were observed in the incidence of CINV, pattern of CINV, or severity of nausea by type of 5HT3RA in triplet antiemetic prophylaxis with DEX-sparing strategy. In both groups, the incidence of nausea gradually increased from day 3, peaked on day 4 or 5, and then declined slowly. The visual analog scale scores in the delayed phase remained high throughout the 7-day observation period. CONCLUSION: Careful patient selection and symptom monitoring are needed when implementing the DEX-sparing strategy in triplet antiemetic prophylaxis for patients undergoing CBDCA-based chemotherapy. Furthermore, additional strategies may be needed to achieve better control of delayed CINV.

Prophylactic Penehyclidine Inhalation for Prevention of Postoperative Pulmonary Complications in High-risk Patients: A Double-blind Randomized Trial.

BACKGROUND: Postoperative pulmonary complications are common. Aging and respiratory disease provoke airway hyperresponsiveness, high-risk surgery induces diaphragmatic dysfunction, and general anesthesia contributes to atelectasis and peripheral airway injury. This study therefore tested the hypothesis that inhalation of penehyclidine, a long-acting muscarinic antagonist, reduces the incidence of pulmonary complications in high-risk patients over the initial 30 postoperative days. METHODS: This single-center double-blind trial enrolled 864 patients age over 50 yr who were scheduled for major upper-abdominal or noncardiac thoracic surgery lasting 2 h or more and who had an Assess Respiratory Risk in Surgical Patients in Catalonia score of 45 or higher. The patients were randomly assigned to placebo or prophylactic penehyclidine inhalation from the night before surgery through postoperative day 2 at 12-h intervals. The primary outcome was the incidence of a composite of pulmonary complications within 30 postoperative days, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis. RESULTS: A total of 826 patients (mean age, 64 yr; 63% male) were included in the intention-to-treat analysis. A composite of pulmonary complications was less common in patients assigned to penehyclidine (18.9% [79 of 417]) than those receiving the placebo (26.4% [108 of 409]; relative risk, 0.72; 95% CI, 0.56 to 0.93; P = 0.010; number needed to treat, 13). Bronchospasm was less common in penehyclidine than placebo patients: 1.4% (6 of 417) versus 4.4% (18 of 409; relative risk, 0.327; 95% CI, 0.131 to 0.82; P = 0.011). None of the other individual pulmonary complications differed significantly. Peak airway pressures greater than 40 cm H2O were also less common in patients given penehyclidine: 1.9% (8 of 432) versus 4.9% (21 of 432; relative risk, 0.381; 95% CI, 0.171 to 0.85; P = 0.014). The incidence of other adverse events, including dry mouth and delirium, that were potentially related to penehyclidine inhalation did not differ between the groups. CONCLUSIONS: In high-risk patients having major upper-abdominal or noncardiac thoracic surgery, prophylactic penehyclidine inhalation reduced the incidence of pulmonary complications without provoking complications.

[Experience of using a triple fixed combination in the treatment of patients with chronic obstructive pulmonary disease].

AIM: To evaluate the effectiveness of a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate in the treatment of chronic obstructive pulmonary disease (COPD) patients with frequent exacerbations. MATERIALS AND METHODS: The study included 46 patients with severe and extremely severe COPD (GOLD 34) with frequent exacerbations. All patients were divided into 2 groups. The 1st group included 22 COPD patients with a content of eosinophils in the peripheral blood of 300 cells/ml, the 2nd group included 24 COPD patients with no signs of eosinophilic inflammation in the peripheral blood. Group 1 patients were recommended therapy with a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate at a dose of 22/55/92 mcg 1 time per day, group 2 patients received vilanterol+umeclidinium bromide at a dose of 22/55 mcg 1 time per day. The duration of follow-up was 12 months. RESULTS: After 12 months of treatment with a fixed triple combination of vilanterol/umeclidinium bromide/fluticasone furoate, a statistically significant decrease in peripheral blood eosinophilia was noted in patients with COPD with frequent exacerbations and peripheral blood eosinophilia (p=0.001), as well as a decrease in shortness of breath on the MMRs scale (p=0.001) and the frequency of exacerbations in patients with COPD with frequent exacerbations and eosinophilia (p=0.001). CONCLUSION: The use of a fixed combination of vilanterol/umeclidinium bromide/fluticasone furoate for 12 months allowed to reduce the impact of the disease, improve respiratory function and quality of life in COPD patients with eosinophilia.

Efficacy of umeclidinium/vilanterol according to the degree of reversibility of airflow limitation at screening: a post hoc analysis of the EMAX trial.

BACKGROUND: In patients with chronic obstructive pulmonary disease (COPD), the relationship between short-term bronchodilator reversibility and longer-term response to bronchodilators is unclear. Here, we investigated whether the efficacy of long-acting bronchodilators is associated with reversibility of airflow limitation in patients with COPD with a low exacerbation risk not receiving inhaled corticosteroids. METHODS: The double-blind, double-dummy EMAX trial randomised patients to umeclidinium/vilanterol 62.5/25 µg once daily, umeclidinium 62.5 µg once daily, or salmeterol 50 µg twice daily. Bronchodilator reversibility to salbutamol was measured once at screening and defined as an increase in forced expiratory volume in 1 s (FEV1) of ≥ 12% and ≥ 200 mL 10-30 min post salbutamol. Post hoc, fractional polynomial (FP) modelling was conducted using the degree of reversibility (mL) at screening as a continuous variable to investigate its relationship to mean change from baseline in trough FEV1 and self-administered computerised-Transition Dyspnoea Index (SAC-TDI) at Week 24, Evaluating Respiratory Symptoms-COPD (E-RS) at Weeks 21-24, and rescue medication use (puffs/day) over Weeks 1-24. Analyses were conducted across the full range of reversibility (-850-896 mL); however, results are presented for the range -100-400 mL because there were few participants with values outside this range. RESULTS: The mean (standard deviation) reversibility was 130 mL (156) and the median was 113 mL; 625/2425 (26%) patients were reversible. There was a trend towards greater improvements in trough FEV1, SAC-TDI, E-RS and rescue medication use with umeclidinium/vilanterol with higher reversibility. Improvements in trough FEV1 and reductions in rescue medication use were greater with umeclidinium/vilanterol compared with either monotherapy across the range of reversibility. Greater improvements in SAC-TDI and E-RS total scores were observed with umeclidinium/vilanterol versus monotherapy in the middle of the reversibility range. CONCLUSIONS: FP analyses suggest that patients with higher levels of reversibility have greater improvements in lung function and symptoms in response to bronchodilators. Improvements in lung function and rescue medication use were greater with umeclidinium/vilanterol versus monotherapy across the full range of reversibility, suggesting that the dual bronchodilator umeclidinium/vilanterol may be an appropriate treatment for patients with symptomatic COPD, regardless of their level of reversibility.

A randomized controlled trial of long-acting muscarinic antagonist and long-acting ß2 agonist fixed-dose combinations in patients with chronic obstructive pulmonary disease.

BACKGROUND: In chronic obstructive pulmonary disease (COPD) patients, combination treatment with long-acting muscarinic antagonist (LAMA) and long-acting ß2 agonist (LABA) increases forced expiratory volume in one second and reduces symptoms compared to monotherapy. In Japan, three different once-daily fixed-dose combinations (FDCs) have been prescribed since 2015, although a direct comparison of these FDCs has never been performed. The objective of the present study was to compare the effectiveness, preference, and safety of three LAMA/LABA FDCs-glycopyrronium/indacaterol (Gly/Ind), umeclidinium/vilanterol (Ume/Vil), and tiotropium/olodaterol (Tio/Olo)-in patients with COPD. METHODS: We enrolled 75 COPD outpatients (male:female ratio, 69:6; 77.4 ± 6.9 years). A prospective, randomized, crossover study was conducted on three groups using three FDCs: Gly/Ind; Ume/Vil; and Tio/Olo. Each medication was administered for 4 weeks before crossover (total 12 weeks). After each FDC administration, a respiratory function test and questionnaire survey were conducted. A comparative questionnaire survey of all three LAMA/LABA FDCs was conducted after 12 weeks (following administration of final FDC). RESULTS: No significant differences in COPD Assessment Test or modified Medical Research Council dyspnea questionnaire were reported in the surveys completed after each FDC administration; no significant differences in spirometric items were observed. In the final comparative questionnaire survey, patients reported better actual feeling of being able to inhale following Gly/Ind administration compared with Tio/Olo, although no significant differences in adverse events or other evaluations were reported. CONCLUSIONS: The three LAMA/LABA FDCs administered to COPD patients show similar effects and safety, although some minor individual preference was reported. Trial registration This study retrospectively registered with the University Hospital Medical Information Network Clinical Trials Registry (number UMIN000041342, registered on August 6, 2020).

Time-to-first exacerbation, adherence, and medical costs among US patients receiving umeclidinium/vilanterol or tiotropium as initial maintenance therapy for chronic obstructive pulmonary disease: a retrospective cohort study.

BACKGROUND: Adherence to chronic obstructive pulmonary disease (COPD) maintenance medication is important for managing symptoms and exacerbation risk, and is associated with reduced mortality, hospitalizations, and costs. This study compared on-treatment exacerbations, medical costs, and medication adherence in patients with COPD initiating treatment with umeclidinium/vilanterol (UMEC/VI) or tiotropium (TIO). METHODS: This retrospective matched cohort study selected patients from Optum's de-identified Clinformatics Data Mart database who initiated maintenance treatment with UMEC/VI or TIO between 01/01/2014 and 12/31/2017 (index date defined as the first dispensing). Eligible patients were ≥ 40 years of age and had ≥ 12 months continuous health plan coverage pre- and post-index; ≥ 1 medical claim for COPD pre-index or on the index date; no moderate/severe COPD-related exacerbations on the index date; no asthma diagnosis pre- or post-index; no maintenance medication fills containing inhaled corticosteroids, long-acting ß2-agonists, or long-acting muscarinic antagonists pre-index or on the index date; and no fills for both UMEC/VI and TIO on the index date. Outcomes included time-to-first (Kaplan-Meier analysis) and rates of on-treatment COPD-related moderate/severe exacerbations, medication adherence (proportion of days covered [PDC] and proportion of adherent patients [PDC ≥ 0.8]), and COPD-related medical costs per patient per month (PPPM). Propensity score matching was used to adjust for potential confounders. RESULTS: Each cohort included 3929 matched patients. Kaplan-Meier rates of on-treatment COPD-related exacerbations were similar between cohorts (hazard ratio at 12 months; overall: 0.93, moderate: 0.92, severe: 1.07; all p > 0.05). UMEC/VI versus TIO initiators had significantly higher adherence (mean PDC: 0.44 vs 0.37; p < 0.001; proportion with PDC ≥ 0.8: 22.0% vs 16.4%; p< 0.001) and significantly lower mean on-treatment COPD-related total medical costs ($867 vs $1095 PPPM; p = 0.028), driven by lower outpatient visit costs. CONCLUSIONS: These findings provide valuable information for physicians considering UMEC/VI or TIO as initial maintenance therapy options for patients with COPD.

The effect of exacerbation history on outcomes in the IMPACT trial.

IMPACT, a 52-week, randomised, double-blind trial, assessed the efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) triple therapy versus FF/VI or UMEC/VI in patients with symptomatic COPD and a history of exacerbations.Subgroup analyses assessed whether the efficacy of FF/UMEC/VI versus FF/VI or UMEC/VI and UMEC/VI versus FF/VI varies according to prior exacerbation history, and the combined effects of exacerbation history and blood eosinophil counts. Three subgroups were defined: single moderate (1 moderate/no severe; n=3056 (30%)), frequent moderate (≥2 moderate/no severe; n=4628 (45%)) and severe (≥1 severe/any moderate; n=2671 (26%)). End-points included annual on-treatment moderate/severe exacerbation rate (pre-specified), lung function and health status (both post-hoc).Moderate/severe exacerbation rates (reduction % (95% CI)) were reduced in the FF/UMEC/VI group versus FF/VI (single moderate 20% (10-29), frequent moderate 11% (2-19), severe 17% (7-26)) and versus UMEC/VI (single moderate 18% (5-29), frequent moderate 29% (21-37), severe 26% (14-35)). Moderate/severe exacerbation rates were reduced in the FF/VI group versus UMEC/VI in the frequent moderate subgroup; a numerical reduction was observed in the severe subgroup (single moderate 2% (-12-18), frequent moderate 21% (11-29), severe 11% (-3-22)). Moderate/severe exacerbation rates were lower in the FF/VI group compared with UMEC/VI in patients with higher eosinophil counts. FF/UMEC/VI improved lung function and health status versus both dual therapies irrespective of exacerbation subgroup. UMEC/VI improved lung function versus FF/VI in all subgroups.Triple therapy was more effective than dual regardless of exacerbation history, consistent with results in the intent-to-treat population. Comparisons between dual therapies were influenced by prior exacerbation history and eosinophil counts.

Single-inhaler triple therapy fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol and umeclidinium/vilanterol in patients with COPD: results on cardiovascular safety from the IMPACT trial.

BACKGROUND: This analysis of the IMPACT study assessed the cardiovascular (CV) safety of single-inhaler triple therapy with fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI dual therapy. METHODS: IMPACT was a 52-week, randomized, double-blind, multicenter Phase III study comparing the efficacy and safety of FF/UMEC/VI 100/62.5/25 mcg with FF/VI 100/25 mcg or UMEC/VI 62.5/25 mcg in patients ≥40 years of age with symptomatic chronic obstructive pulmonary disease (COPD) and ≥1 moderate/severe exacerbation in the previous year. The inclusion criteria for the study were intentionally designed to permit the enrollment of patients with significant concurrent CV disease/risk. CV safety assessments included proportion of patients with and exposure-adjusted rates of on-treatment CV adverse events of special interest (CVAESI) and major adverse cardiac events (MACE), as well as time-to-first (TTF) CVAESI, and TTF CVAESI resulting in hospitalization/prolonged hospitalization or death. RESULTS: Baseline CV risk factors were similar across treatment groups. Overall, 68% of patients (n = 7012) had ≥1 CV risk factor and 40% (n = 4127) had ≥2. At baseline, 29% of patients reported a current/past cardiac disorder and 58% reported a current/past vascular disorder. The proportion of patients with on-treatment CVAESI was 11% for both FF/UMEC/VI and UMEC/VI, and 10% for FF/VI. There was no statistical difference for FF/UMEC/VI versus FF/VI or UMEC/VI in TTF CVAESI (hazard ratio [HR]: 0.98, 95% confidence interval [CI]: 0.85, 1.11; p = 0.711 and HR: 0.92, 95% CI: 0.78, 1.08; p = 0.317, respectively) nor TTF CVAESI leading to hospitalization/prolonged hospitalization or death (HR: 1.19, 95% CI: 0.93, 1.51; p = 0.167 and HR: 0.96, 95% CI: 0.72, 1.27; p = 0.760, respectively). On-treatment MACE occurred in ≤3% of patients across treatment groups, with similar prevalence and rates between treatments. CONCLUSIONS: In a symptomatic COPD population with a history of exacerbations and a high rate of CV disease/risk, the proportion of patients with CVAESI and MACE was 10-11% and 1-3%, respectively, across treatment arms, and the risk of CVAESI was low and similar across treatment arms. There was no statistically significant increased CV risk associated with the use of FF/UMEC/VI versus FF/VI or UMEC/VI, and UMEC/VI versus FF/VI. TRIAL REGISTRATION: NCT02164513 (GSK study number CTT116855).

Penehyclidine Hydrochloride Premedication Is Not Associated with Increased Incidence of Post-Operative Cognitive Dysfunction or Delirium:A Systemic Review and Meta-Analysis.

Objective Post-operative cognitive dysfunction (POCD) and post-operative delirium (POD) are two common post-operative cerebral complications. The current meta-analysis was to systematically review the effects of penehyclidine hydrochloride (PHC) on POCD and POD in surgical patients.Methods Electronic databases were searched to identify all randomized controlled trials comparing PHC with atropine/scopolamine/placebo on POCD and POD in surgical patients. Primary outcomes of interest included the incidences of POCD and POD; the secondary outcomes of interest included peri-operative mini-mental state examination (MMSE) scores. Two authors independently extracted peri-operative data, including patients' baseline characteristics, surgical variables, and outcome data. For dichotomous data (POCD and POD occurrence), treatment effects were calculated as odds ratio (OR) and 95% confidential interval (CI). Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity. For continuous variables (MMSE scores), treatment effects were calculated as weighted mean difference (WMD) and 95% CI. Statistical significance was defined as P<0.05.Results Our search yielded 33 studies including 4017 patients. Meta-analysis showed that, the incidence of POCD in PHC group was comparable to that in saline group (OR=0.97; 95% CI: 0.58-1.64; P=0.92), scopolamine group (OR=0.78; 95% CI: 0.48-1.27; P=0.32) and atropine group (OR=1.20; 95% CI: 0.86-1.67; P=0.29). The incidence of POD in PHC group was comparable to that in saline group (OR=1.53; 95% CI: 0.81-2.90; P=0.19) and scopolamine group (OR=0.53; 95% CI: 0.06-4.56; P=0.56), but higher than that in atropine group (OR=4.49; 95% CI: 1.34-15.01; P=0.01).Conclusions PHC premedication was not associated with increased incidences of POCD or POD as compared to either scopolamine or placebo.

[Efficacy of Antiemetic Therapy with Aprepitant, Palonosetron, and Dexamethasone in Patients Receiving Oxaliplatin-Based Chemotherapy].

Antiemetic therapy with aprepitant, palonosetron, and dexamethasone is recommended for moderately emetogenic chemotherapy in several guidelines to prevent chemotherapy-induced nausea and vomiting. There is a lack of information about the efficacy and safety of antiemetic therapy with aprepitant, palonosetron, and dexamethasone in patients treated with oxaliplatin in Japan. We recruited patients with untreated colorectal cancer who underwent oxaliplatin-based chemotherapy. All patients were treated with aprepitant, palonosetron, and dexamethasone. The complete response and complete protection rates were analyzed. A total of 52 patients were enrolled in this clinical trial. The complete response rate overall, and in the acute and delayed phases was 92.3%, 98.1%, and 92.3%, respectively. The complete protection rate overall and in the acute and delayed phases was 73.1%, 86.5%, and 73.1%, respectively. Grade 3-4 non-hematological toxicity did not occur. Antiemetic therapy with aprepitant, palonosetron, and dexamethasone is effective and safe in patients treated with oxaliplatin.

Assessment of pre-operative maropitant citrate use in macaque (Macaca fasicularis & Macaca mulatta) neurosurgical procedures.

BACKGROUND: Retrospective analysis of post-operative vomiting (POV) in non-human primates at our institution was 11%. Based on this additional risk factor for post-operative complications, we aimed to eliminate or decrease POV by adding an antiemetic, maropitant citrate, to the pre-medication protocol. METHODS: Retrospective and prospective data were collected over a 5-year period from 46 macaques of two species during 155 procedures. Additionally, blood was collected from five Macaca mulatta to perform a pharmacokinetic analysis. RESULTS: A 1 mg/kg subcutaneous dose of maropitant given pre-operatively significantly decreased POV. Findings indicated post-neurosurgical emesis in Macaca fasicularis was significantly greater than in Macaca mulatta. Pharmacokinetic analysis of maropitant in Macaca mulatta determined the mean maximum plasma concentration to be 113 ng/mL. CONCLUSIONS: Maropitant administration prior to anesthesia for neurosurgeries decreased our incidence of POV to 1%. The plasma concentration reaches the proposed plasma level for clinical efficacy approximately 20 minutes after administration.

Palonosetron is nonsuperior to ondansetron in acute phase but provides superior antiemetic control in delayed phase for pediatric patients administered highly emetogenic chemotherapy.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) in children remains to be a major side effect despite antiemetic treatment. Palonosetron is a new generation 5-HT3 receptor antagonists effective against acute and delayed nausea and vomiting. This study aimed to compare the therapeutic values of palonosetron and ondansetron in preventing pediatric CINV. METHODS: A prospective, randomized, double-blind, parallel controlled study was conducted in 0-18 years old cancer patients administered highly emetogenic chemotherapy, with different dosage of palonosetron or ondansetron, both followed by dexamethasone. The patients were observed for vomiting and nausea from 0 to 120 hr after chemotherapy initiation. All adverse events (AEs) during the study period were recorded. This study was registered with the Chinese Clinical Trial Registry, number ChiCTR-TRC-14004891. RESULTS: Between August 2014 and July 2016, 565 patients were randomly assigned to receive 5 µg/kg palonosetron (n = 185), 10 µg/kg palonosetron (n = 186), and 3 × 150 µg/kg ondansetron (n = 194), of whom 181, 185, and 189, respectively, were included in the efficacy analysis. Complete response (CR) rates during the acute phase were 69.1, 69.7, and 64.6%, respectively, in the 5 µg/kg palonosetron, 10 µg/kg palonosetron, and ondansetron groups. In the delayed phase, 10 µg/kg palonosetron (CR, 53.5%) showed superiority to 5 µg/kg palonosetron (CR, 39.8%) and ondansetron (CR, 32.8%) groups (P < 0.05). The most frequently observed drug-related AEs were nervous system disorders, mainly headache, with an incidence of 2.8, 2.2, and 2.6% in each group, respectively. CONCLUSION: Combination of palonosetron plus dexamethasone is highly effective in controlling acute and delayed CINV, with palonosetron superior to ondansetron.

A phase 2a randomized controlled study to evaluate the pharmacokinetic, safety, tolerability and clinical effect of topically applied Umeclidinium in subjects with primary axillary hyperhidrosis.

BACKGROUND: Hyperhidrosis is a common medical condition which can have a significant impact on quality of life. Umeclidinium (UMEC) is a long-acting muscarinic antagonist (LAMA) developed as a dermal formulation. OBJECTIVES: This 2-week, double-blind, randomized, vehicle-controlled study evaluated systemic exposure, safety and tolerability of topically administered UMEC in subjects with primary axillary hyperhidrosis. Clinical effect was a secondary objective, measured by gravimetry and the hyperhidrosis disease severity scale (HDSS). Vehicle was included to evaluate safety. METHODS: Twenty-three subjects were randomized to either 1.85% UMEC (N = 18) or vehicle (N = 5) once daily. RESULTS: Measurable plasma concentrations were observed in 78% of subjects after the treatment. Nine subjects (50%) on UMEC and two subjects (40%) on vehicle reported AEs, most commonly application site reactions. At Day 15, seven subjects (41%) in UMEC and two subjects (40%) in vehicle had at least a 50% reduction in sweat production. Eight subjects (47%) in UMEC and one subject (20%) in vehicle had at least a two-point reduction in HDSS. No comparisons of treatment arms were planned prospectively. CONCLUSIONS: The measurable exposure, acceptable safety and preliminary clinical activity observed in this proof-of-concept study suggest the potential clinical utility of topical UMEC in subjects with axillary hyperhidrosis.

Palonosetron compared with ondansetron in pediatric cancer patients: multicycle analysis of a randomized Phase III study.

AIM: To investigate across multiple cycles the efficacy and safety of palonosetron in the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients receiving highly or moderately emetogenic chemotherapy (HEC/MEC). PATIENTS & METHODS: Patients were randomly assigned to 10, 20 µg/kg palonosetron or 3 × 150 µg/kg ondansetron for up to four cycles of HEC/MEC. RESULTS: In all on-study chemotherapy cycles, complete response rates were higher in patients in the 20 µg/kg palonosetron group than the ondansetron group. Treatment-emergent adverse events were comparable between the palonosetron 20 µg/kg and ondansetron groups. CONCLUSION: Over four cycles of HEC/MEC, 20 µg/kg palonosetron was an efficacious and safe treatment for the prevention of chemotherapy-induced nausea and vomiting in pediatric cancer patients.

Comparison between Antiemetic Effects of Palonosetron and Granisetron on Chemotherapy-Induced Nausea and Vomiting in Japanese Patients Treated with R-CHOP.

In the present study, the antiemetic effect of palonosetron, not combined with dexamethasone and aprepitant, on chemotherapy-induced nausea and vomiting was evaluated in patients with malignant lymphoma receiving first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy, and was compared to that of granisetron. A total of 74 patients with non-Hodgkin lymphoma were included in this study (April 2007 to December 2015). Palonosetron (0.75 mg) or granisetron (3 mg) was intravenously administered before R-CHOP therapy. The proportions of patients with complete response (CR) during the overall (0-120 h after the start of R-CHOP therapy), acute (0-24 h) and delayed (24-120 h) phases were evaluated. CR was defined as no vomiting and no use of antiemetic rescue medication. A total of 32 and 42 patients were treated with palonosetron and granisetron, respectively. The CR rate in the palonosetron group was significantly higher than that in the granisetron group during the delayed phase (90.6 and 61.9%, respectively; p=0.007). Logistic regression analysis showed that use of palonosetron improved the CR rate during the delayed phase, compared to use of granisetron. Female sex, age less than 60 years, no habitual alcohol intake, and Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 1 were significant risk factors associated with non-CR. The findings of this study suggested the superiority of palonosetron to granisetron, without accompanying dexamethasone and aprepitant, for chemotherapy-induced nausea and vomiting in patients with malignant lymphoma.