Search

Purpose: This review is an update of the MASCC/ESMO 2015 recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting. Methods: A systematic literature search was conducted using PubMed from June 1, 2015, through February 1, 2023. Results: We identified 56 references (16 were duplications or invalid), leaving 40 manuscripts for this search. The panel classified level I evidence (three manuscripts) and level II evidence (14 manuscripts). High-dose chemotherapy and stem cell transplant were discussed in four of these manuscripts, and multiple-day chemotherapy treatment in 15. Some manuscripts covered both topics. Additionally, a search for breakthrough nausea and vomiting resulted in 12 “hits.” No new relevant studies were identified. Conclusions: The recommendations for patients receiving high-dose chemotherapy with stem cell transplants and patients undergoing multiple-day cisplatin were updated. For patients receiving high-dose chemotherapy for stem cell transplant, a combination of a 5-HT3 receptor antagonist with dexamethasone and aprepitant is recommended. Olanzapine could be considered part of the antiemetic regimen. Patients receiving multiple-day cisplatin should receive a 5-HT3 receptor antagonist plus dexamethasone plus aprepitant plus olanzapine. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests using a single dose of olanzapine daily for 3 days. [ABSTRACT FROM AUTHOR]

Background: In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was designed to assess the efficacy and safety of granisetron in patients with sepsis. Methods: Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome. Results: The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49–1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups. Conclusion: Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration. [ABSTRACT FROM AUTHOR]

Background. Chemotherapy-induced nausea and vomiting (CINV) is a troublesome side-effect of chemotherapy in pediatric patients undergoing osteosarcoma treatment. In this context, the role of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists needs to be explored. Objectives. To evaluate the superiority of single-dose palonosetron over granisetron in pediatric patients undergoing highly emetogenic chemotherapy (HEC) for osteosarcoma. Materials and methods. In this double-blind, randomized study, pediatric patients were assessed in terms of acute nausea and vomiting following HEC for osteosarcoma. These children were assigned to group 1 (palonosetron) and group 2 (granisetron) without any other antiemetic prophylaxis. The primary outcome variable was the children's segment with a complete response (CR) during the acute phase of the 1st on-study chemotherapy cycle. The risk factors associated with the emesis were analyzed. The patients were followed up for the first 24 h after chemotherapy. Results. A total number of 200 children were evaluated in terms of the response, and other factors that might alter the response were assessed in the 2 groups. These 200 children underwent 604 blocks of chemotherapy. Complete responses were documented in 83% and 72% of children receiving palonosetron and granisetron, respectively, during the acute phase. Only dexamethasone, used as a rescue medication, was found to be a significant risk factor that predisposed to the response (p < 0.05). Conclusions. Single-dose palonosetron is an effective alternative to granisetron for preventing CINV in children receiving HEC for osteosarcoma. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical efficacy of 5-hydroxytryptamine 3 (5-HT3) receptor antagonists in reducing propofol injection pain, postoperative nausea/ vomiting, and shivering through pooling the available published data.

Purpose: This review is an update of the MASCC/ESMO 2015 recommendations for the prophylaxis of acute and delayed nausea and vomiting induced by multiple-day chemotherapy, high-dose chemotherapy, and breakthrough nausea and vomiting., Methods: A systematic literature search was conducted using PubMed from June 1, 2015, through February 1, 2023., Results: We identified 56 references (16 were duplications or invalid), leaving 40 manuscripts for this search. The panel classified level I evidence (three manuscripts) and level II evidence (14 manuscripts). High-dose chemotherapy and stem cell transplant were discussed in four of these manuscripts, and multiple-day chemotherapy treatment in 15. Some manuscripts covered both topics. Additionally, a search for breakthrough nausea and vomiting resulted in 12 "hits." No new relevant studies were identified., Conclusions: The recommendations for patients receiving high-dose chemotherapy with stem cell transplants and patients undergoing multiple-day cisplatin were updated. For patients receiving high-dose chemotherapy for stem cell transplant, a combination of a 5-HT 3 receptor antagonist with dexamethasone and aprepitant is recommended. Olanzapine could be considered part of the antiemetic regimen. Patients receiving multiple-day cisplatin should receive a 5-HT 3 receptor antagonist plus dexamethasone plus aprepitant plus olanzapine. For patients experiencing breakthrough nausea and vomiting, the available evidence suggests using a single dose of olanzapine daily for 3 days., (© 2023. The Author(s).)

This paper presents a literature review of the pharmacology of serotonin. It focuses on the metabolism and transport of serotonin and on 5-HT receptors and their clinical significance. This report highlights the substances that affect serotonin signalling and body levels and may be employed in treating various disorders: either directly, by influencing the serotonin receptors or, indirectly, by inhibiting serotonin reuptake. The review will be published in two separate parts. The first part will contain a short introduction in the pharmacology of serotonin and it will emphasize the pharmacological properties of the first three of the 5-HT receptors (5-HT1, 5-HT2, 5-HT3). In the second part, the other four types of 5-HT receptors (5-HT4, 5-HT5, 5-HT6, 5-HT7) will be presented along with tendencies and prospects in influencing serotonin transporter (SERT) through selective serotonin reuptake inhibitors (SSRIs). Recent research involving serotonin aims to improve the safety and effectiveness of antidepressant therapy. In order to achieve this, scientists are developing drugs that not only target SERT, but can also act as a full or partial agonist or antagonist on certain serotonergic receptors. [ABSTRACT FROM AUTHOR]

Background Two pivotal Phase III trials compared the efficacy of palonosetron, ondansetron and granisetron, combined with dexamethasone, for the prevention of nausea and vomiting following highly emetogenic chemotherapy. However, an economic evaluation of these three regimens in the real-world setting of Chinese adult patients has not been determined. Objectives To estimate, from the perspective of the Chinese healthcare system, which of these frequently used strategies consisting of 0.25 mg palonosetron (0.25P), 16 mg ondansetron (Onda), and 3 mg granisetron (Gran), is the most cost-effective option in patients following highly emetogenic chemotherapy. Methods A Markov decision-analytic model was developed. The health and economic outcomes of the three strategies; 0.25P, Onda, and Gran were investigated. The clinical and utility data were taken from published studies. The cost data were calculated according to current local Chinese practices. Sensitivity analyses were performed to determine the impact of uncertainty regarding the results. Results The base-case analysis showed that the 0.25P strategy yielded maximum health benefits compared with the other two strategies. However, the probabilistic sensitivity analysis demonstrated that the Gran strategy was the most cost-effective approach when the willingness-to-pay threshold was not more than US$22,515/quality-adjusted life year. Moreover, palonosetron is not cost-effective in preventing ‘overall’ nausea and vomiting following highly emetogenic chemotherapy in Chinese patients. Conclusions Our analysis suggests that, compared with palonosetron and ondansetron, 3 mg granisetron may be a cost-effective treatment option in the current Chinese healthcare setting. [ABSTRACT FROM AUTHOR]

The aim of this meta-analysis was to evaluate the preventive efficacy and safety of 5-HT3 receptor antagonists (5-HT3RAs) on perioperative shivering. Relevant databases were searched to identify eligible randomized, controlled trials through January 2016. Primary outcome was the incidence of perioperative shivering, and secondary outcomes were the incidence of safety-related outcomes including postoperative nausea and vomiting (PONV), bradycardia, and hypotension. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous data. Trial sequential analysis was performed to assess the risk of random errors and calculate the required information size. Sixteen studies with a total of 1126 patients were included in the meta-analysis. Compared with the control group, 5-HT3RAs administered intravenously could statistically significantly reduce the incidence of perioperative shivering (RR, 0.44; 95%CI, 0.35 to 0.56; P < .00001; heterogeneity: I2 = 30%) as well as PONV (RR, 0.52; 95%CI, 0.28 to 0.97; P = .04; heterogeneity: I2 = 0%). However, they did not show superiority in lowering the rate of bradycardia (RR, 0.75; 95%CI, 0.38 to 1.49; P = 0.42; heterogeneity: I2 = 0%) or hypotension (RR, 0.79; 95%CI, 0.44 to 1.43; P = .44; heterogeneity: I2 = 24%). Trial sequential analysis of primary outcome showed that the required information size was 2634 patients and that the trial sequential monitoring boundary was crossed. Thus, more high-quality randomized, controlled trials with larger sample sizes are still required to draw a definite conclusion about the preventive efficacy of 5-HT3RAs on perioperative shivering prevention in the future. [ABSTRACT FROM AUTHOR]

Purpose: An update of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy published after the last MASCC/ESMO antiemetic consensus conference in 2009 has been carried out.Methods: A systematic literature search using PubMed from January 1, 2009 to January 6, 2015 with a restriction to papers in English was conducted.Results: Overall, two randomized phase II and seven randomized phase III studies plus the results of three subgroup analysis of large phase III trials and those of a pilot study have been included.Conclusions: In carboplatin-treated patients, a moderate benefit from adding an NK1 receptor antagonist to dexamethasone and a 5-HT3 receptor antagonist has been shown. However, in oxaliplatin-treated patients, contrasting results about the role of NK1 receptor antagonists have been obtained. At present, it is not possible to suggest a specific 5-HT3 receptor antagonist to use for the prevention of acute emesis in these patients. No routine prophylaxis for delayed emesis is recommended but in patients receiving moderately emetogenic chemotherapy with known potential for delayed emesis (e.g., oxaliplatin, doxorubicin, cyclophosphamide) the use of dexamethasone for days 2-3 can be considered. [ABSTRACT FROM AUTHOR]

Background: Consensus guidelines recommend the use of multiple antiemetics as prophylaxis in patients at high risk of postoperative nausea and vomiting (PONV), but the evidence regarding combining acupuncture and antiemetics as a multimodal approach was of very low quality., Objective: This study aimed to assess the effect of combinations of acupuncture with ondansetron versus ondansetron alone for PONV prophylaxis in women at a high risk., Methods: This parallel, randomised controlled trial was conducted in a tertiary hospital in China. Patients who had three or four PONV risk factors on the Apfel simplified risk score, undergoing elective laparoscopic gynaecological surgery for benign pathology, were recruited. Patients in the combination group received two sessions of acupuncture treatment and 8 mg intravenous ondansetron, whereas those in the ondansetron group received ondansetron alone. The primary outcome was the incidence of PONV within 24 h postoperatively. Secondary outcomes included the incidence of postoperative nausea, postoperative vomiting, adverse events etc. RESULTS: Between January and July 2021, a total of 212 women were recruited, 91 patients in the combination group and 93 patients in the ondansetron group were included in the modified intention-to-treat analysis. In the first 24 h postoperatively, 44.0% of the patients in the combination group and 60.2% of the patients in the ondansetron group experienced nausea, vomiting, or both (difference, -16.3% [95% CI, -30.5 to -2.0]; risk ratio, 0.73 [95% CI, 0.55-0.97]; p = 0.03). However, the results of the secondary outcomes showed that compared to ondansetron alone, acupuncture together with ondansetron was only effective in reducing nausea but did not have a significant impact on vomiting. The incidence of adverse events was similar between the groups., Conclusion: Acupuncture combined with ondansetron as a multimodal prophylaxis approach is more effective than ondansetron alone in preventing postoperative nausea in high-risk patients., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

This paper presents a literature review of the pharmacology of serotonin. It focuses on the metabolism and transport of serotonin and on 5-HT receptors and their clinical signifi cance. This report highlights the substances that affect serotonin signalling and body levels and may be employed in treating various disorders: either directly, by influencing the serotonin receptors or, indirectly, by inhibiting serotonin reuptake. The review will be published in two separate parts. The fi rst part will contain a short introduction in the pharmacology of serotonin and it will emphasize the pharmacological properties of the fi rst three of the 5-HT receptors (5-HT1, 5-HT2, 5-HT3). In the second part, the other four types of 5-HT receptors (5-HT4, 5-HT5, 5-HT6, 5-HT7) will be presented along with tendencies and prospects in influencing serotonin transporter (SERT) through selective serotonin reuptake inhibitors (SSRIs). Recent research involving serotonin aims to improve the safety and effectiveness of antidepressant therapy. In order to achieve this, scientists are developing drugs that not only target SERT, but can also act as a full or partial agonist or antagonist on certain serotonergic receptors. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) can lead to increased emergency department visits and hospitalizations, which may contribute to increased cost of care. Antiemetic agents, such as neurokinin-1 (NK1) receptor antagonists and 5-hydroxytryptamine (5-HT3) receptor antagonists, are prescribed for patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). The current guidelines recommend a 3-drug combination of an NK1 receptor antagonist, a 5-HT3 receptor antagonist, and dexamethasone with HEC regimens and certain MEC regimens. OBJECTIVE: To compare the incidence of CINV and CINV-related resource utilization among patients who receive guideline-adherent HEC and MEC regimens and patients who receive non-guideline-adherent regimens. METHODS: In this retrospective, claims-based study, Inovalon's Medical Outcomes Research for Effectiveness and Economics Registry (MORE² Registry) Research Edition database was used to identify 8089 patients with solid tumors receiving therapy with anthracycline plus cyclophosphamide (AC), cisplatin, or carboplatin from June 2013 to December 2013. The patients were stratified according to the use of an NK1 receptor antagonist regimen. International Classification of Diseases, Ninth Revision, Clinical Modification codes were used to identify CINV events associated with hospital, emergency department, and outpatient office visits among patients in the NK1 receptor antagonist group and the non-NK1 receptor antagonist group. RESULTS: A total of 1059 patients were included in the analysis, of whom 51 % (N = 536) used an NK receptor antagonist-based regimen and 49% (N = 523) used non-NK1 receptor antagonist therapy. A higher percentage of patients receiving AC (73%) than cisplatin (56%) or carboplatin (23%) received an NK1 receptor antagonist. The incidence rates of total CINV events and CINV-related emergency department visits were lower in the group receiving an NK1 receptor antagonist (44% and 9%, respectively) than in the group not receiving an NK1 receptor antagonist (50% and 15%, respectively). CONCLUSION: The patients receiving an NK1 receptor antagonists had a lower rate of resource utilization, suggesting that the use of NK1 receptor antagonist-containing regimens according to current national guidelines may reduce healthcare resource utilization, such as CINV-related office, hospital, and emergency department visits for patients receiving highly and moderately emetogenic chemotherapy. [ABSTRACT FROM AUTHOR]

Background 5-HT3 receptor antagonists are effective antiemetics for perioperative use. However, their effects on myometrial contractility remain unknown. We examined whether three different 5-HT3 receptor antagonists could affect the contraction of human myometrium. Methods Samples of human myometrium were taken from parturients undergoing elective cesarean delivery. Effects of ondansetron, granisetron and tropisetron (over a range of 1–10 4 ng/mL) on spontaneous contraction (ratios of amplitude, interval, and duration of the contraction) were examined and compared to saline controls (n=6 for each agent). Results None of the three 5-HT3 receptor antagonists significantly affected myometrial contraction. Conclusion 5-HT3 receptor antagonists do not affect the contraction of myometrial strips isolated from term pregnant women. [ABSTRACT FROM AUTHOR]

Background: In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was designed to assess the efficacy and safety of granisetron in patients with sepsis. Methods: Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome. Results: The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49-1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups. Conclusion: Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Guan, Liao, Guo, Yu, Wei, Niu, Gan, Zhang, Li, Lv, Shichen, Chang, Chen and Liu.)

Background: Chemotherapy-induced nausea and vomiting (CINV) is a troublesome side-effect of chemotherapy in pediatric patients undergoing osteosarcoma treatment. In this context, the role of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists needs to be explored., Objectives: To evaluate the superiority of single-dose palonosetron over granisetron in pediatric patients undergoing highly emetogenic chemotherapy (HEC) for osteosarcoma., Material and Methods: In this double-blind, randomized study, pediatric patients were assessed in terms of acute nausea and vomiting following HEC for osteosarcoma. These children were assigned to group 1 (palonosetron) and group 2 (granisetron) without any other antiemetic prophylaxis. The primary outcome variable was the children's segment with a complete response (CR) during the acute phase of the 1st on-study chemotherapy cycle. The risk factors associated with the emesis were analyzed. The patients were followed up for the first 24 h after chemotherapy., Results: A total number of 200 children were evaluated in terms of the response, and other factors that might alter the response were assessed in the 2 groups. These 200 children underwent 604 blocks of chemotherapy. Complete responses were documented in 83% and 72% of children receiving palonosetron and granisetron, respectively, during the acute phase. Only dexamethasone, used as a rescue medication, was found to be a significant risk factor that predisposed to the response (p < 0.05)., Conclusions: Single-dose palonosetron is an effective alternative to granisetron for preventing CINV in children receiving HEC for osteosarcoma.

Objective: Perioperative shivering (POS) is a common complication in patients undergoing spinal anaesthesia. The present study investigated the efficacy of 5-HT 3 receptor antagonists in preventing POS following spinal anaesthesia., Design: Systematic review and meta-analysis., Data Sources: Pubmed, Embase, the Web of Science and Cochrane Library were searched from database establishment on 31 July 2019., Eligibility Criteria: Randomised controlled trials that reported the effects of 5-HT 3 receptor antagonists in the prevention of POS in patients after spinal anaesthesia., Data Extraction and Synthesis: Two reviewers independently extracted data. The primary outcome of the present study was the incidence of POS. The risk of bias for the included studies was assessed according to the Cochrane Handbook. The quality of primary outcome was evaluated by Grading of Recommendations Assessment, Development and Evaluation. Trial sequential analysis for the primary outcome was performed to reduce the type 1 error caused by repeated meta-analysis and the required information size was calculated., Results: A total of 13 randomised controlled trials consisting of 1139 patients were included. The overall incidence of POS was significantly lower in the 5-HT 3 receptor antagonists group (risk ratio 0.31; 95% CI 0.26 to 0.38; p<0.01; I 2 =0%). Subgroup analysis for different types of 5-HT 3 receptor antagonists and timing of administration produced similar results. Also, patients had a lower incidence of postoperative nausea and vomiting after administrating 5-HT3 receptor antagonists. No statistically significant differences in drug-related adverse effects were observed. Grading of Recommendations Assessment, Development and Evaluation revealed a high level of evidence. The cumulative z-curve crossed the trial sequential monitoring boundary., Conclusions: The present study revealed that prophylactic 5-HT 3 receptor antagonists were an effective measure for reducing the incidence of POS in patients after spinal anaesthesia. However, further studies investigating the different types of surgeries are required., Prospero Registration Number: CRD42019148191., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Patients can benefit from the coadministration of several medications because of the shorter infusion time and more rapid administration. The use of extemporaneously prepared admixtures of dexamethasone sodium phosphate (DSP) and 5-HT 3 receptor antagonists (5-HT3RAs) must be supported by sufficient documentation of their compatibility. The objective of this study was to comprehensively investigate the compatibility of DSP with 5-HT3RAs in infusion solutions., Methods: Admixtures of DSP with six different 5-HT3RAs (ondansetron hydrochloride, tropisetron hydrochloride, dolasetron mesylate, azasetron hydrochloride, palonosetron hydrochloride and ramosetron hydrochloride) were prepared in non-polyvinyl chloride (non-PVC) infusion bags filled with 5% glucose or 0.9% NaCl. Bags were stored at ambient temperature (25±2°C) without protection from light. Samples were taken immediately after preparation (0 hour) and at predetermined intervals (12, 24 and 48 hours after preparation). Particulate matter of admixtures was inspected visually and particles were counted with a particle counter. The pH of each sample was also determined. Drug concentrations were determined with validated high-performance liquid chromatography assays., Results: No visible haze or particulate formation, colour change or gas evolution and no notable changes in pH were observed, and particulate matter was acceptable up to 48 hours. All preparations maintained more than 90.0% of the initial concentration over the study period., Conclusions: All the admixtures of DSP and the 5-HT3RAs studied were compatible and stable for at least 48 hours in a 5% glucose injection or a 0.9% NaCl injection stored in non-PVC infusion bags under ambient conditions., Competing Interests: Competing interests: None declared.

The aim of this meta-analysis was to evaluate the preventive efficacy and safety of 5-HT 3 receptor antagonists (5-HT 3 RAs) on perioperative shivering. Relevant databases were searched to identify eligible randomized, controlled trials through January 2016. Primary outcome was the incidence of perioperative shivering, and secondary outcomes were the incidence of safety-related outcomes including postoperative nausea and vomiting (PONV), bradycardia, and hypotension. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous data. Trial sequential analysis was performed to assess the risk of random errors and calculate the required information size. Sixteen studies with a total of 1126 patients were included in the meta-analysis. Compared with the control group, 5-HT 3 RAs administered intravenously could statistically significantly reduce the incidence of perioperative shivering (RR, 0.44; 95%CI, 0.35 to 0.56; P < .00001; heterogeneity: I 2 = 30%) as well as PONV (RR, 0.52; 95%CI, 0.28 to 0.97; P = .04; heterogeneity: I 2 = 0%). However, they did not show superiority in lowering the rate of bradycardia (RR, 0.75; 95%CI, 0.38 to 1.49; P = 0.42; heterogeneity: I 2 = 0%) or hypotension (RR, 0.79; 95%CI, 0.44 to 1.43; P = .44; heterogeneity: I 2 = 24%). Trial sequential analysis of primary outcome showed that the required information size was 2634 patients and that the trial sequential monitoring boundary was crossed. Thus, more high-quality randomized, controlled trials with larger sample sizes are still required to draw a definite conclusion about the preventive efficacy of 5-HT 3 RAs on perioperative shivering prevention in the future., (© 2016, The American College of Clinical Pharmacology.)

Granisetron transdermal delivery system (GTDS) is the first 5-HT3 drug to be transdermally delivered and represents a convenient alternative to oral and intravenous antiemetics for the treatment of chemotherapy-induced nausea and vomiting. GTDS is effective and well tolerated in patients receiving multiple-day moderate-to-highly emetogenic chemotherapy. In this setting noninferiority studies showed similar efficacy when GTDS was compared with intravenous and oral granisetron and intravenous palonosetron. GTDS has shown good cardiovascular safety; however, special caution is needed in patients at risk for developing excessive QTc interval prolongation and arrhythmias. So far, GTDS has been investigated for intravenous prevention in comparison with granisetron and palonosetron; however, further prospects open the route to future clinical investigations.

Chemotherapy-induced nausea and vomiting (CINV) is a significant clinical issue which affects patients' quality of life as well as treatment decisions. Significant improvements in the control of CINV have occurred in the past 15 years with the introduction of new antiemetic agents: 5-HT3 receptor antagonists, tachykinin NK1 receptor antagonists and olanzapine. Aprepitant was the first NK1 receptor antagonist introduced (2003) for the prevention of CINV in combination with a 5-HT3 receptor antagonist and dexamethasone. Two additional NK1 receptor antagonists, netupitant and rolapitant, were approved by the FDA in 2014 and 2015, respectively. A description of rolapitant and its role in CINV will be presented, along with a comparison to the other NK1 receptor antagonists, aprepitant and netupitant., (Copyright 2016 Prous Science, S.A.U. or its licensors. All rights reserved.)

Fibromyalgia syndrome (FMS) is a chronic disorder characterized by widespread pain and tenderness, accompanied by disturbed sleep, chronic fatigue and multiple additional functional symptoms. FMS continues to pose an unmet need regarding pharmacological treatment and many patients fail to achieve sufficient relief from existing treatments. As FMS is considered to be a condition in which pain amplification occurs within the CNS, therapeutic interventions, both pharmacological and otherwise, have revolved around attempts to influence pain processing in the CNS. In the current review, we present an update on novel targets in the search for effective treatment of FMS.

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. The use of a combination of a 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, dexamethasone, and a neurokinin-1 (NK-1) receptor antagonist has significantly improved the control of acute and delayed emesis in single-day chemotherapy. Palonosetron, a second generation 5-HT3 receptor antagonist with a different half-life, different binding capacity, and a different mechanism of action than the first generation 5-HT3 receptor antagonists, appears to be the most effective agent in its class. Netupitant, is a new NK-1 receptor antagonist with a high binding affinity, a long half-life of 90 hours, is metabolized by CYP3A4, and is an inhibitor of CYP3A4. NEPA is an oral fixed-dose combination of netupitant and palonosetron which has recently been employed in Phase II and Phase III clinical trials for the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy (MEC and HEC). The clinical trials demonstrated that NEPA (300 mg of netupitant plus 0.50 mg of palonosetron) significantly improved the prevention of CINV compared to the use of palonosetron alone in patients receiving either HEC or MEC. The clinical efficacy was maintained over multiple cycles of chemotherapy. NEPA (Akynzeo(®)) has recently been approved by the Food and Drug Administration (FDA) to treat nausea and vomiting in patients undergoing cancer chemotherapy.