The association between ondansetron use and mortality risk of traumatic brain injury patients: a population-based study.

Background: Traumatic brain injury (TBI) patients suffer high risks of mortality. Ondansetron has been verified to be effective in improving the prognosis of some kinds of critically ill patients. We design this study to explore whether ondansetron use is associated with lower risks of mortality among TBI patients. Methods: TBI patients from the Medical Information Mart for Intensive Care-III were collected. The usage of ondansetron, including intravenous injection and oral tablet, since admission to the Beth Israel Deaconess Medical Center between 2001 and 2012 was identified. Univariate and multivariate logistic regression were performed to analyze the relationship between the ondansetron use and mortality of TBI patients. Propensity score matching (PSM) was utilized to generate balanced cohorts of the non-ondansetron use group and ondansetron use group. Sub-group analysis was performed to verify the association between the ondansetron use and mortality of TBI patients in different TBI severity levels after PSM. Results: In TBI cohorts before PSM, the usage incidence of ondansetron was 37.2%. The 30-day mortality was significantly lower in the ondansetron group (p < 0.001). The multivariate logistic regression showed that ondansetron was associated with the lower mortality of TBI patients (p = 0.008). In TBI cohorts after PSM, the 30-day mortality of the ondansetron group was lower than that of the non-ondansetron group, although without statistical significance (p = 0.079). Logistic regression indicated ondansetron use was significantly associated with the lower mortality of moderate-to-severe TBI (p < 0.001) but not mild TBI (p = 0.051). In addition, Cox regression also presented that ondansetron use was significantly associated with the lower mortality of moderate-to-severe TBI (p < 0.001) but not mild TBI (p = 0.052). Conclusion: Ondansetron usage is associated with a lower mortality risk of moderate-to-severe TBI but not mild TBI patients. Ondansetron may be a novel adjunctive therapeutic strategy to improve the prognosis of moderate-to-severe TBI patients.

Network meta-analysis of triple therapy for the prevention and treatment of acute nausea and vomiting caused by emetogenic chemotherapy drugs with moderate and high risk / 中国药房

OBJECTIVE To evaluate the efficacy of the triple therapy of 5-HT3 receptor antagonists， neurokinin-1 receptor antagonists and dexamethasone （referred to as “triple therapy”） in the prevention and treatment of acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI and Wanfang data， randomized controlled trials （RCTs） about triple therapy or 5-HT3 receptor antagonist combined with dexamethasone （referred to as “dual therapy”） were collected during the inception to May 2023. After literature screening， data extraction and literature evaluation， network meta-analysis was performed by using Stata 16.0 software. RESULTS A total of 59 RCTs were included， involving 23 418 patients and 15 interventions. Results of network meta-analysis showed that fosaprepitant + palonosetron + dexamethasone （FPD） was most effective in terms of acute nausea and vomiting control rate， followed by fosaprepitant + granisetron + dexamethasone （FGD） and aprepitant + ramosetron + dexamethasone （AMD）. In terms of acute nausea control rate， FPD was the most effective， followed by aprepitant + palonosetron + dexamethasone （APD） and FGD. In terms of acute vomiting control rate， FPD was the most effective， followed by FGD and APD. CONCLUSIONS Fosaprepitant + palonosetron + dexamethasone is better than other triple therapy or dual therapy in preventing acute nausea and vomiting caused by moderately and highly emetogenic chemotherapy drugs.

An LC-ESI-MS/MS method for determination of ondansetron in low-volume plasma and cerebrospinal fluid: Method development, validation, and clinical application.

Ondansetron is used in clinical settings as an antiemetic drug. Although the animal studies showed its potential effectiveness also in treating neuropathic pain, the results from humans are inconclusive. The lack of efficacy of ondansetron in a subset of patients might be due to the overexpression of P-glycoprotein, which could result in low concentrations of ondansetron in the central nervous system (CNS). A surrogate of the CNS exposure might be drug concentration in the cerebrospinal fluid (CSF), especially in humans, as assessing the drug disposition directly in the patient's brain would be challenging. The study aimed to develop a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine concentrations of ondansetron in human K3EDTA plasma and CSF. Ondansetron was extracted from biological matrices by liquid-liquid extraction. The quantification was performed on a Sciex QTRAP 6500+ mass spectrometer with labeled ondansetron as an internal standard. The calibration range was 0.25-350 ng/mL in plasma and 0.025-100 ng/mL in CSF; for both matrices, 25 µL of samples was required for the assays. The method was validated according to the FDA and EMA guidelines and showed acceptable results. A pilot study confirmed its suitability for clinical samples: after 4-16 mg of intravenous ondansetron, the determined concentrations in plasma were 1.22-235.90 ng/mL, while in CSF - 0.018-11.93 ng/mL. In conclusion, the developed method fulfilled all validation requirements and can be applied to pharmacokinetic studies assessing the CNS ondansetron exposure in humans. The method's advantages, such as a low volume of matrix and a wide calibration range, support its use in a study in which rich sampling and various drug doses are expected.

Population pharmacokinetic analysis of transdermal granisetron in healthy Chinese and Caucasian volunteers.

Granisetron patches are a prolonged delivery transdermal system that is used to prevent Chemotherapy-induced nausea and vomiting (CINV). To date, no pharmacokinetics comparison between Chinese and Caucasian populations has been conducted for granisetron patches. This study focused on the ethnic differences in pharmacokinetics (PK) of granisetron transdermal delivery system (GTDS) between Chinese and Caucasians and the influence of demographic covariates on pharmacokinetics (age, weight, height, body mass index, sex). To achieve this, blood concentration data were collected from 112 Caucasian healthy subjects participating in four clinical trials and 24 Chinese healthy subjects from one clinical trial, after a single application of the granisetron transdermal delivery system. A nonlinear mixed-effects model method of Phoenix NLME software was used to establish a population pharmacokinetic (Pop PK) model for Caucasian subjects. Bootstrap and visual predictive check (VPC) were used to validate the model. Based on the analysis a one-compartment model with first-order absorption and a first-order elimination well described the PK characteristics of GTDS. The apparent systemic clearance was determined to be 31316.3 mL/h and the central compartment volume of distribution was 6299.03 L. None of the five covariates (age, weight, height, body mass index, and sex) included in the Pop PK were significant covariates affecting PK. The final Pop PK model was used to simulate the Caucasian blood concentration by applying the dosing regimen used for the Chinese population. Comparison of the simulated Caucasian PK data with observed clinical PK data from Chinese healthy subjects revealed no significant differences in the main parameters, AUClast and Cavg, between the two groups. These findings suggested that no dose adjustment was required when applied to the Chinese population. In conclusion, this Pop PK study comparing the transdermal patch in Chinese and Caucasian healthy subjects provided valuable insights for optimizing dosage across ethnicities.

Intraoperative 5-HT3 receptor antagonists decrease the prevalence of postoperative delirium in older adults undergoing hip fracture surgery: a single-center retrospective study.

PURPOSE: Postoperative delirium (POD) occurs commonly in older adults, resulting in unfavorable outcomes. Several recent clinical studies have suggested that 5-hydroxytryptamine 3 (5-HT3) receptor antagonists can treat and prevent POD. In this retrospective study, the association between 5-HT3 receptor antagonists and POD was investigated in older adults who underwent hip fracture surgery. METHODS: The electronic medical records of older adults aged ≥ 65 years who underwent hip fracture surgery between January 2011 and June 2018 were reviewed retrospectively. Multivariable logistic regression analysis was used to investigate the association between 5-HT3 receptor antagonists and the occurrence of POD. In addition to the incidence of POD, anesthesia-, surgery-, and patient-related factors related to POD were evaluated. RESULTS: Of the 1025 patients included, 813 (79.3%) were administered 5-HT3 receptor antagonists intraoperatively; 471 (45.9%) were administered ramosetron, and 342 (33.4%) were administered palonosetron. POD was identified in 242 patients (23.6%). Ramosetron and palonosetron reduced the POD incidence by 53% (odds ratio [OR] 0.47; 95% confidence interval [CI] 0.32‒0.71; P < 0.001) and 41% (OR 0.59; 95% CI 0.39‒0.89; P = 0.011), respectively. Additionally, age, American Society of Anesthesiologists physical status class 4, and male were confirmed as risk factors for POD. CONCLUSION: Intraoperative 5-HT3 receptor antagonists may be associated with a reduced risk of POD and can be considered one of the preventive strategies for POD in older adults undergoing hip fracture surgery.

In Silico, In Vitro, and Ex Vivo Biological Activity of Some Novel Mebeverine Precursors.

Irritable bowel syndrome (IBS) is a functional gastroenterological disorder with complex pathogenesis and multifaceted therapy approaches, aimed at alleviating clinical symptoms and improving the life quality of patients. Its treatment includes dietary changes and drugs from various pharmacological groups such as antidiarrheals, anticholinergics, serotonin receptor antagonists, targeting chloride ion channels, etc. The present article is focused on the synthesis and biological evaluation of some mebeverine precursors as potential antispasmodics. METHODS: In silico analysis aimed at predicting the pharmacodynamic profile of the compounds was performed. Based on these predictions, ex vivo bioelectrical activity (BEA) and immunohistochemical effects of the compounds were established. A thorough biological evaluation of the compounds was conducted assessing their in vitro antimicrobial and cytotoxic activity. RESULTS: All the newly synthesized compounds exerted drug-like properties, whereby 3-methyl-1-phenylbutan-2-amine 3 showed a significant change in BEA due to Ca2+ channel regulation, Ca2+ influx modulation, and a subsequent change in smooth muscle cell response. The immunohistochemical studies showed a good correlation with the obtained data on the BEA, defining amine 3 as a leader structure. No cytotoxicity to human malignant leukemic cell lines (LAMA-84, K-562) was observed for all tested compounds. CONCLUSION: Based on the experimental results, we outlined 3-methyl-1-phenylbutan-2-amine 3 as a potential effective choice for orally active long-term therapy of IBS.

Ondansetron in dogs with nausea associated with vestibular disease: A double-blinded, randomized placebo-controlled crossover study.

BACKGROUND: Nausea and emesis can be, among other signs, common manifestations of acute vestibular system dysfunction in dogs. Currently, antiemetic drugs, such as maropitant and metoclopramide, are used commonly, but do not appear to control nausea. A non-placebo-controlled preliminary study suggested good efficacy of 5-HT3-receptor antagonists, such as ondansetron, against nausea in dogs with vestibular syndrome. OBJECTIVES: To assess and confirm the effect of ondansetron on behavior suggestive of nausea in dogs with vestibular syndrome. ANIMALS: Fourteen dogs with vestibular syndrome and clinical signs of nausea presented to a neurology service. METHODS: Placebo-controlled, double-blinded, crossover study. Behavioral assessment was performed hourly for 4 hours using an established numerical rating scale. The criteria salivation, lip licking, vocalization, restlessness, lethargy, and general nausea were scored. The occurrence of emesis was recorded. After scoring at T0 (pre-dose) and T2 (2 hours post-dose) either ondansetron (0.5 mg/kg) or placebo was injected IV. Two hours post-dose, treatments were switched. Blood samples were collected to measure serum arginine vasopressin (AVP) concentration, which previously has been shown to correlate with clinical signs of nausea. RESULTS: Clinical resolution of nausea was observed 1 hour after administration of ondansetron, whereas serum AVP concentration decreased 4 hours after ondansetron administration. CONCLUSION AND CLINICAL IMPORTANCE: Administration of ondansetron IV is beneficial for dogs with nausea secondary to acute vestibular syndrome. Ondansetron substantially and rapidly decreased clinical signs of nausea behavior and stopped emesis.

Netupitant-palonosetron (NEPA) for Preventing Chemotherapy-induced Nausea and Vomiting: From Clinical Trials to Daily Practice.

Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with many anticancer therapies and can negatively impact patients' quality of life and potentially limit the effectiveness of chemotherapy. Currently, CINV can be prevented in most patients with guideline-recommended antiemetic regimens. However, clinicians do not always follow guidelines, and patients often face difficulties adhering to their prescribed treatments. Therefore, approaches to increase guideline adherence need to be implemented. NEPA is the first and only fixed combination antiemetic, composed of netupitant (oral)/fosnetupitant (intravenous) and palonosetron, which, together with dexamethasone, constitute a triple antiemetic combination recommended for the prevention of CINV for patients receiving highly emetogenic chemotherapy and for certain patients receiving moderately emetogenic chemotherapy. Thus, NEPA offers a convenient and straightforward antiemetic treatment that could improve adherence to guidelines. This review provides an overview of CINV, evaluates the accumulated evidence of NEPA's antiemetic activity and safety from clinical trials and real-world practice, and examines the preliminary evidence of antiemetic control with NEPA in daily clinical settings beyond those described in pivotal trials. Moreover, we review the utility of NEPA in controlling nausea and preserving patients' quality of life during chemotherapy, two major concerns in managing patients with cancer.

5-HT3 receptor antagonists decrease the prevalence of postoperative delirium in older patients undergoing orthopedic lower limb surgery.

BACKGROUND: Delirium is an important postoperative complication. Recent research suggested that 5-hydroxytryptamine 3 (5-HT3) receptor antagonists may have clinical effect in the treatment and prevention of delirium. We investigated the association between 5-HT3 receptor antagonists and the occurrence of postoperative delirium (POD). METHODS: Retrospectively, the electronic medical records were reviewed in patients aged ≥ 65 years who underwent orthopedic lower limb surgery under regional anesthesia (spinal or combined spinal-epidural anesthesia) and administered intravenous 0.075 mg palonosetron or 0.3 mg ramosetron prior to the end of surgery between July 2012 and September 2015. POD incidence and anesthesia-, surgery-, and patient-related factors were evaluated. To investigate the association between 5-HT3 receptor antagonists and the occurrence of POD, multivariable logistic regression analysis was performed. RESULTS: Of the 855 patients included, 710 (83%) were administered 5-HT3 receptor antagonists. POD was confirmed in 46 (5.4%) patients. 5-HT3 receptor antagonists reduced the POD incidence by 63% (odds ratio [OR] 0.37; 95% confidence interval [CI], 0.15-0.94; P = 0.04). Moreover, the POD incidence decreased by 72% (OR 0.28, 95% CI 0.10-0.77, P = 0.01) when palonosetron was administered. Other identified risk factors for POD were emergency surgery, older age, hip surgery, lower body mass index, and intraoperative propofol sedation. CONCLUSION: 5-HT3 receptor antagonists may be related with a significantly reduced risk for POD in older patients undergoing orthopedic lower limb surgery. Notably, palonosetron was more effective for POD prevention.

Treatment with Oral Ondansetron for Ultramarathon-Associated Nausea: The TOO FUN Study.

Nausea and vomiting are common for runners during ultramarathons and often contribute to non-finishes. We aimed to determine the efficacy of ondansetron, a commonly used antiemetic, to treat nausea and vomiting in runners during an ultramarathon. Runners who had a previous history of frequent nausea or vomiting during races and entered in 160, 80, and 55 km ultramarathons in 2018 and 2019 were randomized in a double-blind fashion to 4 mg ondansetron or placebo capsules to use if they developed nausea or vomiting during the race with the ability to take three additional doses. Study participants completed a post-race online survey to assess medication use and efficacy. Of 62 study participants, 31 took either ondansetron (20) or placebo (11). In this small study, there were no group differences in those reporting any improvement in nausea and vomiting (p = 0.26) or in the amount of improvement (p = 0.15). We found no evidence that ondansetron capsules improve nausea and vomiting during ultramarathons.

Pharmacokinetics and safety evaluation of oral Palonosetron in Chinese healthy volunteers: A phase 1, open-label, randomized, cross-over study.

PURPOSE: Palonosetron hydrochloride is a specific 5-HT3 receptor antagonist, used to prevent chemotherapy-induced nausea and vomiting (CINV), and is a known chemical entity currently registered in the oral and IV forms in several countries worldwide. METHODS: Single-center, single-dose, 3-treatment, open-label, randomized, 3-period, phase-I cross-over study, conducted in 18 individuals (16 males and 2 females). The primary objective was to assess the pharmacokinetic profile of Palonosetron 0.25, 0.5 and 0.75mg, after a single, oral administration in Chinese male and female healthy volunteers. RESULTS: After administration of a single oral dose of 0.25mg, 0.5mg, or 0.75mg palonosetron in Chinese male and female healthy subjects, plasma palonosetron concentrations reached maximum values (Cmax) of 673 ± 151 pg/mL, 1330 ± 258 pg/mL, and 1990 ± 490 pg/mL, respectively, at 3-5 h (tmax). The plasma elimination half-life for 0.25, 0.5 and 0.75 mg of palonosetron was 41.8±9.72 hours, 44.6±8.59 hours and 42.3±8.51 hours, respectively. Single oral doses of 0.25mg, 0.5mg, or 0.75mg palonosetron were safe and well tolerated among all the 18 subjects involved. CONCLUSIONS: The PK of palonosetron was found to be linear in the dose range of 0.25 to 0.75 mg. Oral palonosetron in doses up to 0.75 mg was well tolerated in healthy Chinese subjects. The PK and safety data obtained from this study were similar to previous phase I studies with IV palonosetron.

5-Hydroxytryptamine-3 receptor antagonist and dexamethasone as prophylaxis for chemotherapy-induced nausea and vomiting during moderately emetic chemotherapy for solid tumors: a multicenter, prospective, observational study.

BACKGROUND: Of patients receiving moderate emetic risk chemotherapy (MEC), 30-90% experience chemotherapy-induced nausea and vomiting (CINV); however, the optimal antiemetic treatment remains controversial. METHODS: In this multicenter, prospective, observational study of adults treated with MEC while receiving chemotherapy for various cancer types in Japan, the enrolled patients kept diaries documenting CINV. All participants received a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. RESULTS: Of the 400 patients enrolled from May 2013 to January 2015, 386 were eligible for evaluation. The median age was 64 (range, 26-84). The overall complete response (CR; no emetic events and no antiemetic measures) rate was 64%. The proportion of patients showing CR was low in the carboplatin (CBDCA)- and oxaliplatin-based chemotherapy groups, especially among women. We showed that the CR rates in men were high in the CBDCA (AUC5) + etoposide (ETP) (80%), capecitabine plus oxaliplatin (CAPOX) (78%), and CBDCA+ paclitaxel (PTX) groups for lung cancer (73%). Total control (TC; no emetic events, no antiemetic measures, and no nausea) and complete control (CC; no emetic events, no antiemetic measures, and less than mild nausea) were achieved in 51 and 61% of patients, respectively. Logistic regression analysis revealed history of motion sickness, history of pregnancy-associated vomiting and CBDCA-based chemotherapy as risk factors for CR and history of motion sickness and history of pregnancy-associated vomiting as risk factors for TC. Additional, Ages ≥65 years is an independent predictive factor for achieving TC. CONCLUSIONS: Our data showed that two antiemetics were insufficient to control CINV in patients receiving CBDCA- or oxaliplatin-based chemotherapy. However, two antiemetics may be sufficiently effective for elderly male patients receiving CBDCA (AUC5) + ETP, CBDCA+PTX for lung cancer, or CAPOX. Additionally, we consider that three antiemetics are necessary for women with colorectal cancer receiving CAPOX. Risk factor analysis related to CR showed that CINV prophylaxis in patients treated with CBDCA-based chemotherapy was generally supportive of the guideline-recommended three antiemetics. However, the control of nausea in patients receiving non-CBDCA-based chemotherapy is a key point to note. The further individualization of antiemetic regimens for patients receiving MEC based on both types of chemotherapy regimens and sex is needed.

Pharmacokinetic Modeling of the Impact of P-glycoprotein on Ondansetron Disposition in the Central Nervous System.

PURPOSE: Modulation of 5-HT3 receptor in the central nervous system (CNS) is a promising approach for treatment of neuropathic pain. The goal was to evaluate the role of P-glycoprotein (Pgp) in limiting exposure of different parts of the CNS to ondansetron (5-HT3 receptor antagonist) using wild-type and genetic knockout rat model. METHODS: Plasma pharmacokinetics and CNS (brain, spinal cord, and cerebrospinal fluid) disposition was studied after single 10 mg/kg intravenous dose. RESULTS: Pgp knockout resulted in significantly higher concentrations of ondansetron in all tested regions of the CNS at most of the time points. The mean ratio of the concentrations between KO and WT animals was 2.39-5.48, depending on the region of the CNS. Male and female animals demonstrated some difference in ondansetron plasma pharmacokinetics and CNS disposition. Mechanistic pharmacokinetic model that included two systemic disposition and three CNS compartments (with intercompartmental exchange) was developed. Pgp transport was incorporated as an efflux from the brain and spinal cord to the central compartment. The model provided good simultaneous description of all data sets, and all parameters were estimated with sufficient precision. CONCLUSIONS: The study provides important quantitative information on the role of Pgp in limiting ondansetron exposure in various regions of the CNS using data from wild-type and Pgp knockout rats. CSF drug concentrations, as a surrogate to CNS exposure, are likely to underestimate the effect of Pgp on drug penetration to the brain and the spinal cord.

Mirtazapine, a dopamine receptor inhibitor, as a secondary prophylactic for delayed nausea and vomiting following highly emetogenic chemotherapy: an open label, randomized, multicenter phase III trial.

Background We examined the efficacy of mirtazapine in preventing delayed nausea and vomiting following highly emetogenic chemotherapy (HEC). Patients and methods Patients who had experienced delayed emesis and would be subsequently scheduled for at least three more cycles of the same chemotherapy were randomly assigned to either a mirtazapine (15 mg daily on days 2-4) or a control group. In addition, both groups received a standard triplet regimen comprising aprepitant, a 5-HT3 receptor antagonist, and dexamethasone (7.5 mg on days 2-4). The chemotherapy regimens were either an epirubicin plus cyclophosphamide regimen or cisplatin-containing regimens. The primary end point was a complete response (no emesis and no rescue treatment) to the delayed phase (25-120 h post-chemotherapy) during Cycle 1. The impact on quality of life (QOL) was assessed using the Functional Living Index-Emesis (FLIE) questionnaire. Results Of 95 enrolled patients, 46 were assigned to the mirtazapine group and 49 to the control group. The complete response rate in the delayed phase during Cycle 1 was significantly higher with mirtazapine than in the control group (78.3% versus 49.0%, P = 0.003). The main adverse effects of mirtazapine were mild to moderate somnolence and weight gain. Mean total FLIE scores were similar between the two arms. Conclusions This is the first randomized prospective study to show that adding mirtazapine has a substantial and statistically significant benefit with good tolerance in patients with breast cancer who have experienced delayed emesis following the same prior HEC. (Trial registration: ClinicalTrials.gov NCT02336750).

Pharmacokinetic profile of the selective 5-HT3 receptor antagonist ondansetron in the rat: an original study and a minireview of the behavioural pharmacological literature in the rat.

The availability of agonists and antagonists to modulate the activity of the 5-hydroxytryptamine (5-HT) type 3 (5-HT3) receptor has renewed interest in its role as a therapeutic target. Ondansetron is a highly selective 5-HT3 receptor antagonist that is well tolerated as an anti-emetic for patients undergoing chemotherapy. Preclinical studies in rat have shown the effects of small doses of ondansetron on cognition, behavioural sensitisation, and epilepsy. However, the pharmacokinetic (PK) profile of ondansetron in rat has not been described, which limits the translational relevance of these findings. Here, we aim to determine, in the rat, the PK profile of ondansetron in the plasma and to determine associated brain levels. The plasma PK profile was determined following acute subcutaneous administration of ondansetron (0.1, 1, and 10 µg/kg). Brain levels were measured following subcutaneous administration of ondansetron at 1 µg/kg. Plasma and brain levels of ondansetron were determined using high-performance liquid chromatography - tandem mass spectrometry. Following administration of all three doses, measured ondansetron plasma levels (≈30-3000 pg/mL) were below levels achieved with doses usually administered in the clinic, with a rapid absorption phase and a short half-life (≈30-40 min). We also found that brain levels of ondansetron at 1 µg/kg were significantly lower than plasma levels, with brain to plasma ratios of 0.45 and 0.46 in the motor and pre-frontal cortices. We discuss our findings in the context of a minireview of the literature. We hope that our study will be helpful to the design of preclinical studies with therapeutic end-points.

Network Meta-analysis of 5-HT3 Receptor Antagonists for Prevention of Acute Nausea and Vomiting Caused by High-dose Chemotherapy / 中国药学杂志

OBJECTIVE: To evaluate the efficacy of 5-HT3 antagonists in the prevention of acute nausea and vomiting caused by high-dose chemotherapy using the network Meta-analysis system. METHODS: Developing retrieval strategies, system retrieves electronic databases such as Pubmed, EMbase, Cochrane Library, VIP, Wanfang and CNKI (as of October 2018), to find a randomized controlled trial (RCT) that uses 5-HT3 receptor antagonist alone to prevent nausea and vomiting caused by high-dose chemotherapy in adults. Quality assessment and data extraction were performed on eligible RCTs, with outcomes including acute nausea and vomiting. The RESULTS of the included RCT studies were combined using traditional STA analysis and network Meta-analysis using STATA13.0 software and WINBUG software.The RESULTS of the included RCT studies were combined using traditional Meta-analysis and network Meta-analysis. RESULTS: A total of 20 studies were included, involving a total of 4 042 patients with high-dose emetogenic chemotherapy.Seven interventions were included (granstron, ondansetron, ramosetron, tropisetron, dolasetron, azasetron, and palonosetron) with a total arm count of 41.The traditional Meta RESULTS showed that palonosetron was more effective in preventing acute nausea and vomiting caused by high-dose chemotherapy than ondansetron, and the difference was statistically significant (P0.05). Ondansetron may be inferior to granisetron (OR=1.238), but the difference is not statistically significant (P>0.05).For acute nausea caused by high-dose chemotherapy, ondansetron may be inferior to granisetron (OR=1.232), but the difference was not statistically significant (P>0.05).Ramosetron may be better than granisetron (OR=0.632), but the difference was not statistically significant (P>0.05).Network Meta-analysis found that ondansetron was inferior to palonosetron in the treatment of acute vomiting due to high-dose chemotherapy (OR=0.60, 95%CI:0.39-0.88). Palonosetron was superior to ramosetron (OR=2.54, 95% CI:1.16-5.80). SCURA RESULTS showed that the best treatment for acute nausea caused by high-dose chemotherapy was palonosetron, followed by ramosetron, dolasetron, ondansetron, granisetron and tropisetron. The best treatment for acute vomiting caused by high-dose chemotherapy is palonosetron, followed by ramosetron, azasetron, dolasetron, tropisetron, granisetron and ondansetron. The RESULTS of the network Meta-analysis are basically consistent with those obtained by traditional Meta-analysis. CONCLUSION: Compared with the first-generation 5-HT3 receptor antagonist, palonosetron is more effective in preventing acute nausea and vomiting caused by high-dose chemotherapy, ramosetron is more effective than other first-generation 5-HT3 receptor antagonists. Whether the RESULTS of this study will guide the clinical practice still requires a large-scale prospective study designed specifically to verify.

Economic analysis of palonosetron versus granisetron in the standard triplet regimen for preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy in Japan (TRIPLE phase III trial).

BACKGROUND: We conducted an economic assessment using test data from the phase III TRIPLE study, which examined the efficacy of a 5-hydroxytryptamine 3 receptor antagonist as part of a standard triplet antiemetic regimen including aprepitant and dexamethasone in preventing chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). METHODS: We retrospectively investigated all medicines prescribed for antiemetic purposes within 120 h after the initiation of cisplatin administration during hospitalization. In the TRIPLE study, patients were assigned to treatment with granisetron (GRA) 1 mg (n = 413) or palonosetron (PALO) 0.75 mg (n = 414). The evaluation measure was the cost-effectiveness ratio (CER) assessed as the cost per complete response (CR; no vomiting/retching and no rescue medication). The analysis was conducted from the public healthcare payer's perspective. RESULTS: The CR rates were 59.1% in the GRA group and 65.7% in the PALO group (P = 0.0539), and the total frequencies of rescue medication use for these groups were 717 (153/413 patients) and 573 (123/414 patients), respectively. In both groups, drugs with antidopaminergic effects were chosen as rescue medication in 86% of patients. The costs of including GRA and PALO in the standard triplet antiemetic regimen were 15,342.8 and 27,863.8 Japanese yen (JPY), respectively. In addition, the total costs of rescue medication use were 73,883.8 (range, 71,106.4-79,017.1) JPY for the GRA group and 59,292.7 (range, 57,707.5-60,972.8) JPY for the PALO group. The CERs (JPY/CR) were 26,263.4 and 42,628.6 for the GRA and PALO groups, respectively, and the incremental cost-effectiveness ratio (ICER) between the groups was 189,171.6 (189,044.8-189,215.5) JPY/CR. CONCLUSIONS: We found that PALO was more expensive than GRA in patients who received a cisplatin-based HEC regimen.

CINV: still troubling patients after all these years.

Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared side effects experienced by patients with cancer. The precise physiologic mechanisms responsible for acute and delayed CINV continue to be elucidated and have provided an opportunity to develop antiemetic therapies targeting these pathways. The emergence of receptor antagonists targeting serotonin and neurokinin-1 have revolutionized the prevention of CINV, significantly reducing the impact of this side effect and improving patient quality of life. However, several areas of unmet need remain, including adequate prevention of nausea, rather than just vomiting, in patients receiving chemotherapy for cancer. Prevention of delayed CINV and anticipatory CINV, as well as management of breakthrough CINV, also continues to challenge patients and clinicians. Ongoing research continues to address these areas to improve antiemetic therapies and guidelines.

Getting it right the first time: recent progress in optimizing antiemetic usage.

Recent years have witnessed significant improvements in the prevention and management of chemotherapy-induced nausea and vomiting (CINV), allowing patients to complete their prescribed chemotherapy regimens without compromising quality of life. This reduction in the incidence of CINV can be primarily attributed to the emergence of effective, well-tolerated antiemetic therapies, including serotonin (5-hydroxytryptamine or 5-HT3) receptor antagonists, neurokinin-1 (NK-1) receptor antagonists, and the atypical antipsychotic olanzapine. While 5-HT3 receptor antagonists are highly effective in the prevention of acute CINV, NK-1 receptor antagonists and olanzapine have demonstrated considerable activity against both acute and delayed CINV. Various combinations of these three types of agents, along with dexamethasone and dopamine receptor antagonists, are now becoming the standard of care for patients receiving moderately or highly emetogenic chemotherapy. Optimal use of these therapies requires careful assessment of the unique characteristics of each agent and currently available clinical trial data.