Palonosetron versus Granisetron in Combination with Aprepitant and Dexamethasone for the Prevention of Chemotherapy-Induced Nausea and Vomiting after Moderately Emetogenic Chemotherapy: A Single-Institutional Retrospective Cohort Study.

The triplet antiemetic regimen is administered to prevent chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC). However, the superiority of palonosetron over first-generation 5-hydroxytryptamine-3 receptor antagonists in triplet antiemetic therapy remains unclear. In this study, we evaluated the efficacy of palonosetron (PALO) and granisetron (GRA) in triplet antiemetic therapy for CINV. This study included 267 patients who received MEC at our hospital between April 2017 and September 2020. Patients were pretreated with antiemetic therapy comprising PALO or GRA and dexamethasone on day 1 and aprepitant on days 1-3. We evaluated the rate of complete response (CR) (i.e., no vomiting and no use of rescue medication) in the acute phase (0-24 h), delayed phase (24-120 h), and overall phase (0-120 h) after first-cycle chemotherapy. Furthermore, multivariate analysis was conducted to identify risk factors for non-CR. The rate of CR in the overall and delayed phases was significantly higher in the PALO group (91.9 and 91.9%, respectively) than in the GRA group (74.1 and 75.5%, respectively). In the acute phase, the incidence was not different between the GRA and PALO groups (96.5 and 99.2%, respectively). Multivariate analysis revealed that female sex and the use of GRA were risk factors for non-CR. Subgroup analysis revealed the superiority of PALO over GRA in female patients, but not in male patients. In conclusion, PALO was more effective than GRA in triplet antiemetic therapy in preventing CINV during MEC, especially for female patients.

NEPA (netupitant/palonosetron) for the antiemetic prophylaxis of nausea and vomiting induced by chemotherapy (CINV) with Folfirinox and Folfoxiri even during the COVID-19 pandemic: a real-life study.

OBJECTIVE: The outbreak of coronavirus disease 2019 (COVID-19) has affected the treatment of cancer patients, with particular regard to the management of both chemotherapy and side effects. Chemotherapy-induced nausea and vomiting (CINV) are amongst the most troublesome side effects that impair patients' adherence to treatments and their quality of life (QoL). NEPA (Akynzeo®), is an oral fixed-dose combination of netupitant [a neurokinin-1 receptor antagonist (NK1RA), 300 mg] and palonosetron [(5-hydroxytryptamine (serotonin or 5HT) type3 receptor antagonist (5HT3RA), 0.5 mg] which has been shown to be effective in preventing CINV. PATIENTS AND METHODS: This prospective study started before the outbreak of COVID-19 and was carried out during the pandemic period. The aim was to evaluate the efficacy and safety of a single oral dose NEPA plus 12 mg of dexamethasone (DEX) in patients treated with Folfoxiri plus Bevacizumab and Folfirinox. The patients were diagnosed with advanced colorectal cancer (CRC) or advanced pancreatic ductal adenocarcinoma (PDAC). They were divided into two groups: naïve patients and patients previously treated with serotonin receptor antagonists (5HT3-RA) and neurokin-1 receptor antagonists (NK1-RA). RESULTS: During the overall phase, the complete response (CR) rate was 96.8% in naïve patients treated with Folfoxiri plus Bevacizumab, and 94.6% in patients treated with Folfirinox. During the acute and delayed phases, the CR rate was 92.8% and 94.2%, with Folfoxiri and Bevacizumab, as well as 96.2% and 94.6%, with Folfirinox. There was no adequate control of CINV events in patients on antiemetic prophylaxis with 5HT3-RA or NK1-RA associated with cortisone. During the overall phase, the CR rate was 74.6% with Folfoxiri plus Bevacizumab and 75.8% with Folfirinox. During the acute and delayed phases, the CR rate was 72.5% and 74.8% with Folfoxiri plus Bevacizumab, as well as 75.2% and 74.6% with Folfirinox. CONCLUSIONS: This study has shown the therapeutic benefits of NEPA in the management and prophylaxis of CINV events, both in naive patients and patients previously treated with 5HT3-RA and NK1-RA. In addition, NEPA has been shown to be safe, both before and during the COVID-19 pandemic.

Comparison of efficacy between palonosetron-midazolam combination and palonosetron alone for prevention of postoperative nausea and vomiting in patients undergoing breast surgery and patient controlled analgesia: A prospective, randomized, double-blind study: A CONSORT-compliant study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common complaint in patients following general anesthesia. Various antiemetics, including 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, are effective but still have limited efficacy. Therefore, combination therapy is preferable to using a single drug alone in high-risk patients. We performed a comparative study on the antiemetic effect of palonosetron, a 5-HT3 receptor antagonist, monotherapy vs palonosetron-midazolam combination therapy for the prevention of PONV. METHODS: A total of 104 female patients scheduled for breast cancer surgery were enrolled. They were randomly divided into 2 groups, a palonosetron monotherapy group (group P) and palonosetron-midazolam combination therapy group (group PM). Both groups received 0.075 mg palonosetron intravenously after induction of anesthesia. Patient-controlled analgesia (PCA) was applied according to the allocated group. Intravenous (IV)-PCA in group P consisted of fentanyl 20 µg/kg plus normal saline (total volume: 100 ml); IV-PCA in group PM consisted of fentanyl 20 µg/kg plus midazolam 4 mg plus normal saline (total volume: 100 ml). Efficacy parameters were collected during 0 to 1, 1 to 6, 6 to 24, and 24 to 48 hours postoperative time intervals. These measures included complete response (defined as no PONV and no rescue anti-emetic use) rate, incidence of PONV, sedation score, rescue antiemetic use, rescue analgesic use, and numerical rating scale (NRS) for pain. The complete response rate during the 0 to 24 hours interval was analyzed as the primary outcome. RESULTS: Although the complete response rate between 0 and 24 hours was higher in group PM (42.3% and 48.1% in group P and PM, respectively), there was no statistically significant difference (P = .55). The complete response rates in other time intervals were not different between the 2 groups as well. The sedation score and NRS score also showed no differences between the 2 groups. CONCLUSIONS: The combination therapy of palonosetron with midazolam did not lead to a greater reduction in the incidence of PONV than monotherapy in patients undergoing breast surgery and receiving IV-PCA containing fentanyl.

Stability of Aprepitant Injectable Emulsion in Alternate Infusion Bags, in Refrigerated Storage, and Admixed with Dexamethasone and Palonosetron.

PURPOSE: The stability of aprepitant injectable emulsion is evaluated in various admixture bags and solutions, under different storage conditions, and when combined with other antiemetics. METHODS: A volume of 18 mL aprepitant injectable emulsion was added to infusion bags (either non-di-(2-ethylhexyl) phthalate [DEHP], polyvinyl chloride [PVC]-containing bags or non-DEHP, non-PVC bags) containing 100, 130, or 250 mL of 0.9% normal saline solution (NSS) or 5% dextrose in water (D5W). Bags were stored at controlled room temperature (20-25°C) for up to 12 hours or refrigerated (2-8°C) for up to 72 hours. Compatibility/stability was also assessed in admixtures combined with either dexamethasone or palonosetron. At specified time points, bags were tested for appearance, pH, assay for aprepitant (ie, percent label claim of aprepitant) and aprepitant-related substances, Z-average particle size, globule size distribution, particulate matter, and DEHP content (PVC bags). In separate analyses to assess microbial burden, bags containing aprepitant were inoculated with seven different organisms and assessed for microbial growth. RESULTS: There was no detectable impact on the physicochemical properties or potential to promote microbial growth of aprepitant when diluted with various amounts of either NSS or D5W and when admixed with either dexamethasone or palonosetron at room temperature for at least 6 hours or during refrigeration for up to 72 hours in either PVC- or non-PVC-containing bags. CONCLUSION: Aprepitant-containing admixtures are stable under these conditions, a finding that may improve patient and provider convenience and reduce medication wastage.

Effects of 5-HT3 receptor antagonists on cisplatin-induced kidney injury.

Nausea, vomiting, and renal injury are the common adverse effects associated with cisplatin. Cisplatin is excreted via the multidrug and toxin release (MATE) transporter, and the involvement of the MATE transporter in cisplatin-induced kidney injury has been reported. The MATE transporter is also involved in the excretion of ondansetron, but the effects of 5-HT3 receptor antagonists used clinically for cisplatin-induced renal injury have not been elucidated. Therefore, the aim of this study was to investigate the effects of 5-HT3 receptor antagonists in a mouse model of cisplatin-induced kidney injury and to validate the results using medical big data analysis of more than 1.4 million reports and a survey of 3000 hospital medical records. The concomitant use of a first-generation 5-HT3 receptor antagonist (ondansetron, granisetron, or ramosetron) significantly increased cisplatin accumulation in the kidneys and worsened renal damage. Conversely, the concomitant use of palonosetron had no effect on renal function compared with the use of cisplatin alone. Furthermore, an analysis of data from the US Food and Drug Administration Adverse Event Reporting System and retrospective medical records revealed that the combination treatment of cisplatin and a first-generation 5-HT3 receptor antagonist significantly increased the number of reported renal adverse events compared with the combination treatment of cisplatin and a second-generation 5-HT3 receptor antagonist. These results suggest that compared with the first-generation antagonists, second-generation 5-HT3 receptor antagonists do not worsen cisplatin-induced acute kidney injury. The findings should be validated in a prospective controlled trial before implementation in clinical practice.

Effects of Palonosetron on Nausea and Vomiting Induced by Multiple-Day Chemotherapy: A Retrospective Study.

Patients who undergo multiple-day chemotherapy sessions experience hard-to-treat nausea and vomiting. Currently, there is no effective standard treatment for this condition. This study compared the preventive effect of first-generation 5-hydroxytryptamine 3 receptor antagonists (5-HT3 RAs) and second-generation 5-HT3 RAs palonosetron in multiple-day chemotherapy-induced nausea and vomiting. The design of this study was a retrospective case-control study of patients who received a five-day cisplatin-based chemotherapy and were treated with aprepitant, dexamethasone, granisetron, and ramosetron or palonosetron. The patients were divided into two groups: patients given granisetron and ramosetron (the first-generation group), and those given palonosetron (palonosetron group). The percentage of patients with a complete response or total control was assessed. They were divided into three phases: 0-216 h (overall phase), 0-120 h (remedial phase), and 120-216 h (after phase). The remedial phase was further divided into 0-24 h (early phase) and 24-120 h (later phase). Moreover, the nutritional status of each patient was assessed by noting the patients' total calorie-intake per day and total parenteral nutrition. First-generation 5-HT3 RAs and palonosetron were used for treatment in 18 and 28 patients, respectively. The complete response rate and caloric oral intake of the later phase were higher in the palonosetron group than in the first-generation group. We conclude that palonosetron treatment was more effective than first-generation 5-HT3 RAs in controlling multiple-day chemotherapy-induced nausea and vomiting.

NEPA as antiemetic prophylaxis after failure of 5HT3-RA plus dexamethasone in patients receiving carboplatin and gemcitabine chemotherapy: A monocentric real-life experience.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) may affect adherence to planned chemotherapy treatments and compromise patients' quality of life during the therapy. NEPA is an oral fixed combination of netupitant, a highly-selective NK1-RA and palonosetron, a 5HT3-RA, approved for the prevention of acute and delayed CINV. The aim of this study was to evaluate the efficacy and safety of NEPA with dexamethasone for CINV prophylaxis in the challenging setting of carboplatin and gemcitabine combination chemotherapy, after failure of prophylaxis with 5HT3 receptor antagonist. METHODS: Eligible patients were undergoing carboplatin and gemcitabine combination chemotherapy for metastatic non-small cell lung cancer (NSCLC), ovarian cancer or urothelial cancer and experienced nausea and/or vomiting after the first cycle of chemotherapy, despite an antiemetic prophylaxis with a 5HT3-RA and dexamethasone. Primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) obtained with NEPA, during the overall phase (0-120 h), after the start of chemotherapy. RESULTS: During the first cycle of chemotherapy, 15 out of 30 (50%) patients did not properly control CINV with a 5HT3-RA plus dexamethasone used as primary antiemetic prophylaxis and then were switched to NEPA from the subsequent cycle. During NEPA administration, 13 out of 15 patients (86.7%) achieved an overall CR (no emesis, no rescue medication). Antiemetic treatment with NEPA was very well tolerated with only two patients (13.3%) that experienced a grade 1 TEAE. CONCLUSIONS: Our experience showed that NEPA has proven to be very effective and well tolerated in the prophylaxis of CINV induced by carboplatin-based chemotherapy.

The next generation of antiemetics for the management of postoperative nausea and vomiting.

Postoperative nausea and vomiting (PONV) afflict approximately 30% of patients overall and up to 80% of high-risk patients after surgery. Optimal pharmacological prophylaxis of PONV is challenging as it necessitates the consideration of PONV risk, drug efficacy, and potential adverse effects. Despite significant advances in our understanding of the pathophysiology and risk factors of PONV, its incidence has remained largely unchanged. Newer antiemetics have been introduced that may have improved safety profiles, longer duration of action, and better efficacy. This review aims to summarize the recent developments pertaining to these new agents and their potential application toward the management of PONV.

[Effect of palonosetron, ondansetron and dexamethasone in the prevention of postoperative nausea and vomiting in video cholecystectomy with total venous anesthesia with propofol-remifentanil - randomized clinical trial]. / Efeito da palonosetrona, ondansetrona e dexametasona na prevenção de náusea e vômito pós­operatório em videocolecistectomia com anestesia venosa total com propofol­remifentanil ­ ensaio clínico randomizado duplo cego.

INTRODUCTION AND OBJECTIVES: The incidence of Postoperative Nausea and Vomiting (PONV) after video cholecystectomy is high. Progress in pharmacological PONV prophylaxis includes a new generation of 5-HT3 antagonists. This study aims to assess the effect of the 5-HT3 antagonist in postanesthetic antiemetic management of patients submitted to laparoscopic cholecystectomy with total intravenous anesthesia. METHODS: Sixty individuals who underwent video cholecystectomy were randomized into three groups of 20 individuals according to the treatment administered: 0.125 mg of palonosetron (Group 1); 4 mg of ondansetron associated with 4 mg of dexamethasone (Group 2); 4 mg of dexamethasone (Group 3). General intravenous anesthesia was performed with propofol, remifentanil and rocuronium. The group to which the participant belonged was concealed from the investigator who assessed drug effect. PONV was assessed using the Rhodes Scale at 12 and 24 hours after surgery. Rescue medication was 0.655 to 1.5 mg of droperidol. RESULTS: Group 1 presented a lower incidence of PONV and required less rescue medication in the first postoperative hour. There was no significant difference among the three groups regarding PONV incidence in the first 12 postoperative hours. Groups 1 and 2 were superior to Group 3 regarding the control of PONV from 12 to 24 hours, and after rescue medication from 12 to 24 hours. Group 1 showed significantly superior nausea control in the first 12 postoperative hours. CONCLUSIONS: The present study showed evidence that palonosetron is superior to the drugs compared regarding a protracted antiemetic effect and less requirement of rescue drugs, mainly related to its ability to completely inhibit the uncomfortable symptom of nausea.

Effect of palonosetron, ondansetron and dexamethasone in the prevention of postoperative nausea and vomiting in video cholecystectomy with total venous anesthesia with propofol-remifentanil - randomized clinical trial / Efeito da palonosetrona, ondansetrona e dexametasona na prevenção de náusea e vômito pós-operatório em videocolecistectomia com anestesia venosa total com propofol-remifentanil - ensaio clínico randomizado duplo cego

Abstract Introduction and objectives: The incidence of Postoperative Nausea and Vomiting (PONV) after video cholecystectomy is high. Progress in pharmacological PONV prophylaxis includes a new generation of 5-HT3 antagonists. This study aims to assess the effect of the 5-HT3 antagonist in postanesthetic antiemetic management of patients submitted to laparoscopic cholecystectomy with total intravenous anesthesia. Methods: Sixty individuals who underwent video cholecystectomy were randomized into three groups of 20 individuals according to the treatment administered: 0.125 mg of palonosetron (Group 1); 4 mg of ondansetron associated with 4 mg of dexamethasone (Group 2); 4 mg of dexamethasone (Group 3). General intravenous anesthesia was performed with propofol, remifentanil and rocuronium. The group to which the participant belonged was concealed from the investigator who assessed drug effect. PONV was assessed using the Rhodes Scale at 12 and 24 hours after surgery. Rescue medication was 0.655 to 1.5 mg of droperidol. Results: Group 1 presented a lower incidence of PONV and required less rescue medication in the first postoperative hour. There was no significant difference among the three groups regarding PONV incidence in the first 12 postoperative hours. Groups 1 and 2 were superior to Group 3 regarding the control of PONV from 12 to 24 hours, and after rescue medication from 12 to 24 hours. Group 1 showed significantly superior nausea control in the first 12 postoperative hours. Conclusions: The present study showed evidence that palonosetron is superior to the drugs compared regarding a protracted antiemetic effect and less requirement of rescue drugs, mainly related to its ability to completely inhibit the uncomfortable symptom of nausea.

Resumo Justificativa e objetivo: Náuseas e Vômitos no Pós-Operatório (NVPO) têm alta incidência após videocolecistectomia. Avanços na profilaxia farmacológica de NVPO incluem a nova geração de antagonista 5-HT3. O objetivo deste estudo foi avaliar o efeito do antagonista 5-HT3 no controle antiemético pós-anestésico em videocolecistectomia com anestesia venosa total. Método: Estudo realizado no HC-UFU (Hospital Terciário). Sessenta indivíduos submetidos a videocolecistectomia foram randomizados em três grupos de igual número, sendo administrados 0,125 mg de palonosetrona (Grupo 1); 4 mg de ondasetrona e 4 mg de dexametasona (Grupo 2); ou 4 mg de dexametasona (Grupo 3). A anestesia geral venosa foi realizada com propofol, remifentanil e rocurônio. O avaliador do efeito da droga desconhecia o grupo ao qual o indivíduo pertencia. NVPO foi avaliada aplicando a Escala de Rhodes após 12 e 24 horas do término da cirurgia. Para resgate terapêutico, foi estabelecido 0,655−1,5 mg de droperidol. Resultado: Observou-se no Grupo 1 menor incidência de NVPO e de resgate terapêutico na primeira hora de PO. Não foi observada diferença significativa entre os três grupos com relação a ocorrência de NVPO nas primeiras 12 horas de pós-operatório. Os grupos 1 e 2 foram superiores ao Grupo 3 no que se refere ao controle de NVPO de 12 a 24 horas e após o resgate de 12−24 horas. Observou-se que o controle de náuseas nas primeiras 12 horas de pós-operatório do Grupo 1 foi significantemente superior. Conclusão: O presente estudo mostrou evidências da superioridade da palonosetrona às demais drogas empregadas no que se refere ao efeito antiemético prolongado e menor necessidade de resgate, principalmente na capacidade de inibir completamente o desconfortável sintoma de náusea.

Comparison of palonosetron-dexamethasone and ondansetron-dexamethasone for prevention of postoperative nausea and vomiting in middle ear surgery: a randomized clinical trial / Comparação entre palonosetrona-dexametasona e ondansetrona-dexametasona na prevenção de náuseas e vômitos no pós-operatório de cirurgia do ouvido médio: estudo clínico randomizado

Abstract Background: Postoperative nausea and vomiting is the second most common complaint in the postoperative period after pain. The incidence of postoperative nausea and vomiting was 60-80% in middle ear surgeries in the absence of antiemetic prophylaxis. Because of this high incidence of postoperative nausea and vomiting, we aimed to assess the effect of palonosetron-dexamethasone and ondansetron-dexamethasone combination for the prevention of postoperative nausea and vomiting in patients of middle ear surgery. Methods: Sixty-four patients, scheduled for middle ear surgery, were randomized into two groups to receive the palonosetron-dexamethasone and ondansetron-dexamethasone combination intravenously before induction of anesthesia. Anesthesia technique was standardized in all patients. Postoperatively, the incidences and severity of nausea and vomiting, the requirement of rescue antiemetic, side effects and patient satisfaction score were recorded. Results: Demographics were similar in the study groups. The incidence difference of nausea was statistically significant between groups O and P at a time interval of 2-6 hours only (p = 0.026). The incidence and severity of vomiting were not statistically significant between groups O and P during the whole study period. The overall incidence of postoperative nausea and vomiting (0-24 hours postoperatively) was 37.5% in group O and 9.4% in group P (p = 0.016). Absolute risk reduction with palonosetron-dexamethasone was 28%, the relative risk reduction was 75%, and the number-needed-to-treat was 4. The patient's satisfaction score was higher in group P than group O (p = 0.016). The frequency of rescue medication was more common in group O than in group P patients (p = 0.026). Conclusion: The combination of palonosetron-dexamethasone is superior to ondansetron-dexamethasone for the prevention of postoperative nausea and vomiting after middle ear surgeries.

Resumo Justificativa: Náusea e vômito no pós-operatório é a segunda queixa pós-operatória mais frequente após a dor. Sem profilaxia antiemética, a incidência de náusea e vômito no pós-operatório foi de 60−80% após cirurgia do ouvido médio. Dada a alta incidência relatada de náusea e vômito no pós-operatório, nosso objetivo foi avaliar o efeito da combinação de palonosetrona-dexametasona e ondansetrona-dexametasona na prevenção de náusea e vômito no pós-operatório em pacientes submetidos a cirurgia do ouvido médio. Método: Sessenta e quatro pacientes programados para cirurgia de ouvido médio foram aleatoriamente divididos em dois grupos. Um recebeu a combinação de palonosetrona-dexametasona (grupo P) e o outro ondansetrona-dexametasona (grupo O) por via intravenosa antes da indução anestésica. A técnica anestésica foi padronizada em todos os pacientes. No pós-operatório, foram registradas incidência e gravidade das náuseas e vômitos, necessidade de antiemético de resgate, efeitos colaterais e índice de satisfação dos pacientes. Resultados: As características demográficas foram semelhantes nos grupos estudados. A diferença na incidência de náusea foi estatisticamente significante entre os grupos O e P apenas no intervalo de tempo entre 2 e 6 horas (p = 0,026). A incidência e gravidade de vômito não foram estatisticamente significantes entre os grupos O e P durante todo o período do estudo. A incidência geral de náusea e vômito no pós-operatório (0−24 horas de pós-operatório) foi de 37,5% no grupo O e de 9,4% no grupo P (p = 0,016). A combinação palonosetrona-dexametasona associou-se com redução do risco absoluto de 28%, redução do risco relativo de 75%, e o número necessário para tratar foi 4. O escore de satisfação do paciente foi maior no grupo P (p = 0,016). A frequência da medicação de resgate foi mais comum no grupo O (p = 0,026). Conclusão: A combinação de palonosetrona-dexametasona é superior à ondansetrona-dexametasona na prevenção da náusea e vômito no pós-operatório após cirurgia de ouvido médio.

[Comparison of palonosetron-dexamethasone and ondansetron-dexamethasone for prevention of postoperative nausea and vomiting in middle ear surgery: a randomized clinical trial]. / Comparação entre palonosetrona­dexametasona e ondansetrona­dexametasona na prevenção de náuseas e vômitos no pós­operatório de cirurgia do ouvido médio: estudo clínico randomizado.

BACKGROUND: Postoperative nausea and vomiting is the second most common complaint in the postoperative period after pain. The incidence of postoperative nausea and vomiting was 60-80% in middle ear surgeries in the absence of antiemetic prophylaxis. Because of this high incidence of postoperative nausea and vomiting, we aimed to assess the effect of palonosetron-dexamethasone and ondansetron-dexamethasone combination for the prevention of postoperative nausea and vomiting in patients of middle ear surgery. METHODS: Sixty-four patients, scheduled for middle ear surgery, were randomized into two groups to receive the palonosetron-dexamethasone and ondansetron-dexamethasone combination intravenously before induction of anesthesia. Anesthesia technique was standardized in all patients. Postoperatively, the incidences and severity of nausea and vomiting, the requirement of rescue antiemetic, side effects and patient satisfaction score were recorded. RESULTS: Demographics were similar in the study groups. The incidence difference of nausea was statistically significant between groups O and P at a time interval of 2-6hours only (p=0.026). The incidence and severity of vomiting were not statistically significant between groups O and P during the whole study period. The overall incidence of postoperative nausea and vomiting (0-24hours postoperatively) was 37.5% in group O and 9.4% in group P (p=0.016). Absolute risk reduction with palonosetron-dexamethasone was 28%, the relative risk reduction was 75%, and the number-needed-to-treat was 4. The patient's satisfaction score was higher in group P than group O (p=0.016). The frequency of rescue medication was more common in group O than in group P patients (p=0.026). CONCLUSION: The combination of palonosetron-dexamethasone is superior to ondansetron-dexamethasone for the prevention of postoperative nausea and vomiting after middle ear surgeries.

Comparison of two different intravenous serotonin antagonists used for chemotherapy-induced nausea and vomiting prophylaxis in patients treated with moderately emetogenic risk regimens: A retrospective analysis from a large academic medical center.

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) can be a serious and debilitating adverse effect that is highly feared by cancer patients. For patients receiving moderately emetogenic chemotherapy regimens at our institution in the ambulatory infusion center, palonosetron was selected as the preferred serotonin (5-HT3) antagonist for CINV prophylaxis per the 2016 NCCN Guidelines, when a neurokinin1 antagonist was not included in the prophylactic regimen. The purpose of this study was to evaluate the efficacy of dexamethasone and palonosetron versus granisetron for the prevention of CINV in patients receiving moderately emetogenic chemotherapy regimens. METHODS: This study is an Institutional Review Board-approved, single-center retrospective review of electronic health records including patients who received moderately emetogenic chemotherapy regimens with CINV prophylaxis with dexamethasone and either palonosetron or granisetron. RESULTS: A total of 268 eligible patients were included in the study. Eighty-eight patients received palonosetron and 180 patients received granisetron as their 5-HT3 receptor antagonist between October 31, 2014 and October 31, 2016. There were no statistically significant differences between the two antiemetic groups for the primary outcome of presence of any change in day 1 intravenous prophylactic antiemetics. Nine (10.23%) palonosetron patients and 15 (8.33%) granisetron patients required a change in their day 1 intravenous prophylactic antiemetics (P = 0.610). CONCLUSIONS: Despite palonosetron's better efficacy, longer half-life, and higher binding affinity, the results of this retrospective review demonstrates that the choice of serotonin antagonist, palonosetron or granisetron, did not result in a change in day 1 intravenous prophylactic antiemetics or antiemetic outpatient medications for patients undergoing moderately emetogenic chemotherapy regimens.

Oral versus intravenous palonosetron in Chinese cancer patients receiving moderately emetogenic chemotherapy: A non-inferiority phase III trial.

OBJECTIVE: The 5-hydroxytryptamine-3 receptor antagonist palonosetron (PALO) is approved (United States/Europe) as an oral formulation for prevention of chemotherapy-induced nausea and vomiting in adult cancer patients undergoing moderately emetogenic chemotherapy (MEC) for the acute phase only, in the United States, or as intravenous (IV) formulation in patients undergoing MEC or highly emetogenic chemotherapy. This phase III study compares the efficacy/safety of oral versus IV PALO in Chinese patients. METHODS: Chemotherapy-naive patients with solid tumours scheduled for MEC received oral PALO 0.50 mg or IV PALO 0.25 mg. The primary objective was to demonstrate non-inferiority in terms of patients with complete response in the acute phase (0-24 hr post-chemotherapy). RESULTS: Complete response rates (acute phase), evaluated in 318/320 randomised patients, were 84.6% and 85.9% for oral and IV PALO respectively. Non-inferiority was demonstrated; the two formulations showed similar efficacy/safety. CONCLUSION: Non-inferiority of oral versus IV PALO in the acute phase was demonstrated in Chinese patients. CLINICAL TRIAL REGISTRATION: CTR20140711.

Real-world evidence of NEPA, netupitant-palonosetron, in chemotherapy-induced nausea and vomiting prevention: effects on quality of life.

Aim: To determine quality of life, effectiveness and safety of oral netupitant-palonosetron (NEPA)-based antiemetic prophylaxis in the real-world setting. Materials & methods: Prospective, noninterventional study in adults receiving highly or moderately emetogenic chemotherapy and NEPA for three cycles. NEPA was administered per summary of product characteristics. Results: A total of 2429 patients enrolled, 2173 were evaluable. 'No impact on daily life' due to vomiting was reported by 85%/82% of patients in the highly emetogenic chemotherapy/moderately emetogenic chemotherapy groups in cycle 1, with rates of 54%/59% for nausea. Overall, complete response rate was 89%/87%/83% in the acute/delayed/overall phases. NEPA was well tolerated. Conclusion: NEPA had beneficial effects on the quality of life of a heterogeneous group of cancer patients and was safe and effective in the real-world setting.

Netupitant/palonosetron (NEPA) and dexamethasone for prevention of emesis in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide: a multi-cycle, phase II study.

BACKGROUND: NEPA is an oral fixed-dose combination of netupitant, a new highly selective neurokinin-1 receptor antagonist, and palonosetron. This study was conducted to evaluate whether the efficacy of NEPA against chemotherapy-induced nausea and vomiting (CINV) in cycle 1 would be maintained over subsequent chemotherapy cycles in breast cancer patients receiving adjuvant anthracycline plus cyclophosphamide (AC). The study also describes the relationship between efficacy on day 1 through 5 (overall period) and control of CINV on day 6 through 21 (very late period) in each cycle. METHODS: In this multicentre, phase II study, patients received both NEPA and dexamethasone (12 mg intravenously) just before chemotherapy. The primary efficacy endpoint was overall complete response (CR; no emesis and no rescue medication use) in cycle 1. Sustained efficacy was evaluated during the subsequent cycles by calculating the rate of CR in cycles 2-4 and by assessing the probability of sustained CR over multiple cycles. The impact of both overall CR and risk factors for CINV on the control of very late events (vomiting and moderate-to-severe nausea) were also examined. RESULTS: Of the 149 patients enrolled in the study, 139 were evaluable for a total of 552 cycles; 97.8% completed all 4 cycles. The proportion of patients with an overall CR was 70.5% (90% CI, 64.1 to 76.9) in cycle 1, and this was maintained in subsequent cycles. The cumulative percentage of patients with a sustained CR over 4 cycles was 53%. NEPA was well tolerated across cycles. In each cycle, patients with CR experienced a significantly better control of very late CINV events than those who experienced no CR. Among the patients with CR, the only predictor for increased likelihood of developing very late CINV was pre-chemotherapy (anticipatory) nausea (adjusted odds ratio = 0.65-0.50 for no CINV events on cycles 3 and 4). CONCLUSION: The high anti-emetic efficacy seen with the NEPA regimen in the first cycle was maintained over multiple cycles of adjuvant AC for breast cancer. Preliminary evidence also suggests that patients achieving a CR during the overall period gain high protection even against very late CINV events in each chemotherapy cycle. TRIAL REGISTRATION: This trial was retrospectively registered at Clinicaltrials.gov identifier (NCT03862144) on 05/Mar/2019.

Extrapolation of Adult Efficacy to Pediatric Patients With Chemotherapy-Induced Nausea and Vomiting.

Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unnecessary clinical trials, improve efficiency, and increase the likelihood of success in obtaining a pediatric indication. The acceptability of the use of extrapolation depends on a series of evidence-based assumptions regarding the similarity of disease, response to intervention, and exposure-response relationships between adult and pediatric patients. This study evaluated publicly available summaries of data submitted to the US Food and Drug Administration for drugs approved for CINV to assess the feasibility of extrapolation for future development programs. Extracted data included trial design, emetogenic potential of chemotherapy, primary end points, participant enrollment criteria, and antiemetic pharmacokinetics. Adult and pediatric clinical trial designs for assessment of efficacy and safety shared key design elements. Antiemetic drugs found to be efficacious in adults were also efficacious in pediatric patients. Systemic drug concentrations at approved doses were similar for ondansetron, granisetron, and aprepitant, but an exposure-response analysis of palonosetron in children suggested that higher palonosetron systemic exposure is necessary for the prevention of CINV in the pediatric population. For 5-hydroxytryptamine-3 and neurokinin-1 receptor antagonist antiemetic drugs, efficacy in adults predicts efficacy in children, supporting the extrapolation of effectiveness of an antiemetic product in children from adequate and well-controlled studies in adult patients with CINV.

Design of a zero-order sustained release PLGA microspheres for palonosetron hydrochloride with high encapsulation efficiency.

Efficient encapsulation of hydrophilic drugs was substantially challenging when using emulsion solvent evaporation approach. The aim of present study was to design palonosetron hydrochloride-loaded PLGA microspheres (Pal-MS) with high encapsulation efficiency (EE) to sustain drug release for over several days. Pal-MS were prepared using emulsion-solvent evaporation method. Results showed that the pH of external phase could significantly affect the EE and the drug release rate of Pal-MS. By increasing the pH of external phase from 5.0 to 10.0, EE of Pal-MS increased from 55.64% to 94.33%. When the pH of external phase was 7.0, an ideal Pal-MS with EE of 86.51% and a zero-order drug release profile was obtained. The improved EE and drug release performance was proved to be associated with possible PLGA degradation, enhanced drug-PLGA interaction and reduced drug diffusion from organic phase to aqueous phase. After subcutaneous injection, such Pal-MS showed more steady drug plasma concentration (0.207-1.238 ng/ml) over the entire 6-day in comparison with those of multiple-day-dosing intravenous palonosetron hydrochloride solution. It was concluded that Pal-MS were successfully designed by the adjustment of the pH of external phase and could be promising for preventing both acute and delayed chemotherapy-induced nausea and vomiting (CINV).

Safety profile of HTX-019 administered as an intravenous push in cancer patients: a retrospective review.

Objectives: HTX-019 (Cinvanti®) is a novel injectable emulsion formulation of the neurokinin 1 receptor antagonist (RA) aprepitant, approved (as 30-min infusion and 2-min injection) for preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV). This retrospective analysis evaluated the safety of HTX-019 administered by 2-min injection in patients with cancer.Methods: At a single center, HTX-019 was evaluated as a 2-min injection within a guideline-recommended three-drug regimen for CINV prophylaxis in patients receiving highly (HEC) or moderately emetogenic chemotherapy (MEC). Treatment-emergent adverse events (TEAEs) were assessed 0-60 minutes following initiation of HTX-019 administration, focusing on infusion-site adverse events and hypersensitivity reactions.Results: Among 600 patients (78 MEC, 522 HEC), the most common diagnoses were lung (172) and breast (129) cancer. Patients received a 2-min injection of HTX-019, followed by a 5-hydroxytryptamine type 3 RA intravenously (IV) (palonosetron or ondansetron), dexamethasone IV, and chemotherapy regimen (most common was cisplatin-containing) via a central (76%) and peripheral line (24%). No TEAEs occurred within 60 min after start of HTX-019 administration.Conclusion: HTX-019 administered by 2-min injection has a tolerable safety profile in patients with cancer, representing a viable method of HTX-019 administration for CINV prevention.