Prevention Of Chemotherapy-induced Nausea And Vomiting Research Articles

A nurse-led multidomain intervention to improve the management of chemotherapy-induced nausea and vomiting in patients with head and neck cancers: A randomized controlled trial

PurposeThis study aimed to investigate the effect of a nurse-led multidomain intervention on chemotherapy induced nausea and vomiting (CINV) in patients with head and neck squamous cell carcinomas (HNSCC). MethodsNinety-two HNSCC patients who received cisplatin-based chemotherapy were divided into intervention group (n = 45) and control group (n = 47). The control group received usual care of CINV, which consisted of administration of antiemetics according to physicians' preference, education about CINV control and dietary recommendations provided by primary nurses. The intervention group received nurse-led, evidence-based multidomain management, including nurse-led CINV risk factors assessment, education on prevention and control of CINV, antiemetics following guidelines, dietary strategies, and relaxation therapy. The number of patients who experienced CINV was collected. The severity of CINV was graded according to the Common Terminology Criteria for Adverse Events v3.0. The influence of CINV on patient's quality of life was assessed by the Functional Living Index-Emesis (FLIE). ResultsThe incidence and the severity of nausea and vomiting in the intervention group were significantly lower than those in the control group within 5 days after chemotherapy, and the scores of the dimension of nausea and vomiting in the intervention group were significantly higher than those in the control group [63.00 (50.00–63.00) vs 40.00(28.00–63.00), 63.00(63.00–63.00) vs 63.00 (43.00–63.00)], the differences were statistically significant (P < 0.05). ConclusionsNurse-led multidomain intervention can reduce the incidence and the severity of CINV in patients with HNSCC who were treated with cisplatin-based chemotherapy, and thus reduced the influence of CINV on patients' quality of life. The clinical trial registration numberNCT05792228.

2020 ASCO, 2023 NCCN, 2023 MASCC/ESMO, and 2019 CCO: a comparison of antiemetic guidelines for the treatment of chemotherapy-induced nausea and vomiting in cancer patients.

Chemotherapy-induced nausea and vomiting (CINV) is a common toxicity that may impair the quality of life of patients with various malignancies ranging from early to end stages. In light of frequent changes to the guidelines for optimal management of CINV, we undertook this narrative review to compare the most recent guidelines published by ASCO (2020), NCCN (2023), MASCC/ESMO (2023), and CCO (2019). The processes undertaken by each organization to evaluate existing literature were also described. Although ASCO, NCCN, MASCC/ESMO, and CCO guidelines for the treatment and prevention of CINV share many fundamental similarities, the literature surrounding low and minimal emetic risk regimens is lacking. Current data regarding adherence to these guidelines is poor and warrants further investigation to improve care.

Evaluation of aprepitant as an add-on therapy for prevention of chemotherapy induced nausea and vomiting in children

Background: Chemotherapy-induced nausea and vomiting (CINV), represents a common and distressing side effect associated with antineoplastic treatment in pediatric patients. Aprepitant, a selective neurokinin-1 receptor antagonist, is recommended for preventing CINV in combination with a standard antiemetic regimen in children undergoing chemotherapy. This study aimed to evaluate the effectiveness of aprepitant as an add-on therapy to the standard antiemetic regimen for the prevention of CINV in children. Methods: This randomized control study was conducted in the BSMMU, Dhaka, Bangladesh from February 2020 to October 2020. Forty-six children with malignancy undergoing chemotherapy were divided into two arms: the Aprepitant arm (23 patients receiving granisetron, dexamethasone, and aprepitant) and the control arm (23 patients receiving Granisetron and Dexamethasone). Data were analyzed using SPSS version 22.0. Results: The complete response rates for the aprepitant versus control arm during the acute and overall phase were 82% vs. 40% (p=0.003) and 65% vs. 26% (p=0.008), respectively. However, a higher percentage of patients who achieved complete response in the delayed phase was also observed, though statistically not significant (65% vs 40%, p=0.077). In the acute phase, there was a significant reduction in mild to moderate vomiting in the Aprepitant arm as compared to the control arm (p=0.01). In the overall phase, 35% of patients in the Aprepitant arm had mild to moderate vomiting as compared to 74% in the control group (p=0.027). No major adverse effects were reported by patients or caregivers. Conclusions: Adding Aprepitant to the standard antiemetic regimen was effective and safe in preventing CINV, especially in the acute phase, in pediatric patients receiving the moderately and highly emetogenic chemotherapy (HEC).

Retrospective Evaluation of a Dexamethasone Sparing Antiemetic Regimen: An Antiemetic Prophylaxis Study on NEPA (Netupitant Plus Palonosetron) for Preventing Chemotherapy-Induced Nausea and Vomiting (CINV) in Cancer Patients.

Background Corticosteroids, specifically dexamethasone (DEX), have been extensively utilized for the prevention of chemotherapy-induced nausea and vomiting (CINV). However, their usage is associated with a range of adverse events. In contrast, the combination of NetupitantPlus Palonosetron (NEPA) with a single dose of DEX provides comparable efficacy in preventing CINV over a five-day period following chemotherapy administration. This regimen offers the advantage of reducing the need for additional doses of DEX, particularly in the high-risk setting of HEC (Highly emetic chemotherapy). Objective To evaluate dexamethasone sparing anti-emetic regimen (single dose dexamethasone with NEPA) for prophylaxis of CINV in patients receiving HEC. Methodology This is a retrospective, observational, real-world, single-center study including data of 69 patients who received high-dose emetogenic chemotherapy and were administered DEX (8 or 12 mg) on day 1, with no dose ofDEX on days 2, 3, and 4, combined with an oral combination of tablet netupitant 300 mg and palonosetron 0.5 mg. NEPA was taken orally an hour prior to the start of the HEC cycle. The primary efficacy endpoint was complete response (CR) which is defined as no nausea, emesis, or no rescue medication during the Acute (< 24 hours) and Delayed Phase (25-120 hours) of chemotherapy. Results The overall CR achieved in the acute and delayed phase for vomiting is 100% at all four follow-ups. The CR achieved in the acute phase is 95.7% whereas 98.6% of patients showed CR in the delayed phase respectively. No patient required any rescue medication. No acute and delayed phase of vomiting was reported. Conclusion A simplified regimen of NEPA plus single-dose DEX offers effective CINV prevention throughout five days post-chemotherapy with the advantage of sparing patients additional doses of DEX in the high-emetic-risk setting chemotherapy.

Evaluation of palonosetron, fosaprepitant, and olanzapine as antiemetic prophylaxis for fludarabine and melphalan-based conditioning regimens prior to allogeneic hematopoietic stem cell transplants

BackgroundLimited data are available regarding efficacious antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). In patients aged 60 years or older, allogeneic HSCT is associated with improved survival, but tolerability of the transplant is a significant barrier. Fludarabine and melphalan (Flu–Mel) is a frequently utilized multi-day reduced intensity conditioning regimen for allogeneic HSCT. However, the optimal CINV prevention regimen is unknown. ObjectiveThe purpose of this study was to evaluate the efficacy of a novel CINV prophylaxis regimen prior to allogeneic HSCT with Flu–Mel compared to a historical control group. Study designThis was a retrospective, single-center, cohort review of 123 patients who received a Flu–Mel preparative regimen prior to allogeneic HSCT from January 1, 2019, to September 30, 2022. Fifty-nine patients received high dose ondansetron (HDO) for CINV prevention, while sixty-four patients received a combination of palonosetron, fosaprepitant, and olanzapine (PFO). The primary outcome was average number of rescue antiemetic doses administered per day. A key secondary outcome was time to first rescue antiemetic. ResultsThe median number of antiemetic doses used per day was significantly lower in patients who received PFO compared to HDO (1.94 doses [0.31–3.60] vs 3.31 doses [1.61–4.92]; p = 0.002). In addition, use of PFO significantly prolonged the median time to first rescue antiemetic compared to HDO (41.3 h [24.3–122.7] vs 26.2 h [14.7–48.1]; p = 0.016). ConclusionThe combination of palonosetron, fosaprepitant, and olanzapine is an effective antiemetic regimen for patients receiving a Flu–Mel-based preparative regimen.

Prevention of CINV in Patients with Multiple Myeloma or Lymphoma Undergoing Hematopoietic Stem Cell Transplantation: NEPA Versus Ondansetron. a Monocentric Real-Life Experience

INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) are adverse events that compromise quality of life and treatment compliance in patients undergoing autologous hematopoietic stem cell transplantation (ASCT). Polychemotherapy regimens, used as conditioning regimens for ASCT in lymphomas, and high-dose melphalan (≥140 mg/mq), used in multiple myeloma (MM), have high emetogenic risk. Control of CINV is difficult and there is no uniformity for its prophylaxis. Antiemetic guidelines recommend, for prophylaxis, co-administration of a triplet regimen of a serotonine (5-HT3) receptor antagonist (RA), as Ondansetron, a neurokinin-1 RA, and dexamethasone. Netupitant-Palonosetron (NEPA), an oral formulation derived from the combination of Netupitant (NK1-RA) and Palonsetron, has been approved as prophylaxis of CINV but its experience in the stem cell transplant setting is still limited. AIMS: The primary aim of this study was to compare the efficacy of Ondansetron versus NEPA in terms of reduction of CINV in patients affected by lymphoma or MM who undergone ASCT. The secondary aims included comparing the duration of CINV, based on the use of Ondansetron or NEPA, and their safety profile in terms of reduction of extrahaematological toxicity (as mucositis or diarrhea). METHODS: In this retrospective monocentric study, we enrolled 76 patients (48 with MM and 28 with lymphoma), who underwent ASCT between March 2021 and March 2022. All patients with MM received high dose of melphalan, those with lymphoma received FEAM. Regarding antiemetics patients were divided according to whether they received NEPA or Ondansetron .Patients' characteristics are in Table 1. RESULTS: Among all, fifty patients (65%) reported CINV of any grade. In particular, the group experiencing CINV included about half of patients treated with NEPA (56%) and almost all those treated with Ondansetron (91%). Among the 26 patients who didn't report CINV (35%), the majority received NEPA (92%) (P = 0.0032)(Fig. 1a). Focusing on patients with MM, 33 experienced CINV (68%), and they were 59% of MM patients treated with NEPA and 93% of those treated with Ondansetron. Fifteen patients did not experience CINV (32%) and almost all of them (93%) had been treated with NEPA (P = 0.037)(Fig. 1b). Sixty-one percent of the 28 patients with lymphoma reported CINV (P= 0.1914) (Fig. 1c). Mean duration of CINV was significantly shorter for patients treated with NEPA than for those treated with Ondansetron (4.8 days vs 9.2 days) (P= 0.002) (Fig. 1d). Regarding extraematological toxicity of chemotherapy, as mucositis and diarrhea, we didn't find any significant difference between the two groups of patients. Regarding the outcome to NEPA, complete response rate (no emesis, no rescue medication) was 37% during overall phases of CINV, 28% of patients had complete control (complete response with no more than mild nausea) and 31% had uncontrolled nausea. Conversely, in the Ondansetron group, only 5% of patients had complete response and 95% had uncontrolled nausea (Fig. 1e). All patients with uncontrolled nausea required a rescue therapy. According to CTCAE, 69% of patients receiving NEPA had grade 1 nausea and 6% had none, while all patients receiving Ondansetron had CINV and 85% of them had grade 2 nausea. CONCLUSIONS: In our experience, NEPA has shown superiority in the prevention of CINV, in highly emetogenic regimens in both patients with myeloma or lymphoma, with advantages on the severity and the duration of CINV. Given the high burden of CINV in the whole population analyzed in the study, regardless of the antiemetic used, it would be useful to identify patients at greatest risk and standardize CINV prophylaxis and treatment protocols depending on the different chemotherapy regimens and their emetogenic risk.

Using Follow-Up Telephone Calls to Identify Obstacles to Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting.

Despite advances in antiemetic regimens, uncontrolled chemotherapy-induced nausea and vomiting (CINV) remains a problem for patients receiving oncology treatment, leading to decreased quality of life and worse treatment outcomes. The purpose of this pilot project was to use follow-up telephone calls to identify barriers related to successful management and prevention of CINV on a single-center outpatient chemotherapy infusion unit. A mixed-methods descriptive design was used for this project. Quantitative data were used to assess barriers to management and prevention of CINV. Secondary multiple regression analysis was used to determine whether barriers could predict CINV. Qualitative data were used to analyze common barriers and themes. Of the patients called (N = 132), 50% identified a barrier to managing and treating CINV, with the most common barrier being knowledge gaps related to proper use of antiemetics.

Efficacy and safety of Aprepitant-containing triple therapy for the prevention and treatment of chemotherapy-induced nausea and vomiting: A meta-analysis.

Most cancer patients suffer from the pain of chemotherapy-induced nausea and vomiting (CINV). This meta-analysis was performed to evaluate the efficacy and safety of a regimen consisting of aprepitant, dexamethasone, and 5-HT3 receptor antagonists in the prevention and treatment of CINV. A systematic literature search was conducted across multiple databases, including PubMed, EMbase, Cochrane Library, MEDLINE, CENTRAL, HEED, CNKI, Wanfang, and VIP, to identify randomized controlled trials (RCTs) investigating the use of triple therapy (aprepitant, 5-HT3 receptor antagonist, and dexamethasone) to prevent and treat CINV. Meta-analysis was performed using RevMan 5.4 and Stata17 software, employing either a fixed-effect or random-effect model based on statistical heterogeneity. A meta-analysis of 23 randomized controlled trials (RCTs) involving 7956 patients was conducted. Efficacy: Results showed significantly improved complete responses (CRs) for CINV in the test group versus the control group in the overall, acute, and delayed phases. Furthermore, in the test group, substantial alleviation of nausea symptoms was observed in the delayed and overall phases but not in the acute phase. Safety: There was no statistically significant difference in the incidence of febrile neutropenia, diarrhea, anorexia, and headache between the 2 groups. The incidence of fatigue and hiccups in the test group was higher than that in the control group; however, the incidence of constipation was significantly lower. Aprepitant-containing triple therapy is highly effective in the prevention and treatment of CINV, with reliable medication safety.

A Randomized Clinical Trial Investigating an Integrated Nursing Educational Program to Mitigate Chemotherapy-Induced Nausea and Vomiting in Cancer Patients: The NIV-EC Trial

Background: In addition to pharmacological prevention, chemotherapy-induced nausea and vomiting (CINV) can be mitigated through patient education; written supporting materials can be beneficial. Methods: This is a randomized, controlled trial which randomly assigned patients undergoing first chemotherapy cycle to receive oral information regarding CINV prevention and management (control arm) or oral information plus an informative booklet (experimental arm). Overall, 384 cancer patients fulfilling the following inclusion criteria were enrolled: age ≥18 years; life expectancy ≥6 months; no cognitive impairment; written informed consent. After the first cycle, CINV occurrence and its impact on daily activities were assessed using the Functional Living Index Emesis (FLIE). Results: Severe nausea was self-reported by 3.0% and 10.8% of patients in the experimental and control group, respectively (difference: 7.8%; 95% confidence interval: 2.3% to 13.1%). Moderate/high impact of nausea on daily activities was lower in patients also receiving the booklet than in the control group (4.2% and 10.1%, respectively; difference: 5.9%; 95% confidence interval: 0.3% to 11.5%). Vomiting was not statistically different between study arms. Conclusions: This integrated nursing approach was effective in aiding cancer patients in CINV self-management. Although the beneficial effect was moderate, this intervention demands minimal resources in terms of costs and time.

Efficacy and safety of 5HT3RA, DEX, and NK1RA for the prevention of FOLFIRINOX-induced nausea and vomiting in patients with pancreatic cancer: a retrospective cohort study.

Modified FOLFIRINOX (mFFX), a standard chemotherapy regimen for advanced pancreatic cancer (APC), is expected to be associated with a higher risk of chemotherapy-induced nausea and vomiting (CINV). Herein, we conducted a retrospective cohort study to evaluate the efficacy and safety of a three-drug combination of 5-hydroxytryptamine-3 receptor antagonists (5HT3RA), dexamethasone (DEX), and neurokinin 1 receptor antagonists (NK1RA) for the prevention of CINV during mFFX therapy. This study enrolled patients with APC who received mFFX as initial therapy with a combination of 5HT3RA, DEX, and NK1RA as antiemetic prophylaxis. The primary endpoint was the complete response (CR) rate during cycle 1, which was defined as no emetic episodes and no rescue medication use during the overall period (0-120h). Safety was also evaluated with a focus on hyperglycemia, which is a concern in patients with APC. Seventy patients were eligible for this retrospective analysis. The CR rate during the overall period was 51.4%. Significant nausea, defined as grade 2 or higher, peaked to 77.1% on days 4-5, but remained above 65% until day 7. Hyperglycemia occurred in 37.1% of patients, and 34.3% were grade 3 hyperglycemia. CINV induced by mFFX was poorly controlled even with prophylactic antiemetic therapy using 5HT3RA, DEX, and NK1RA, and was found to persist beyond 5days. Enhanced antiemetic measures for mFFX are desirable. However, in patients with diabetes mellitus complications, sparing of steroids and glycemic control should be considered.

Olanzapine within steroid-sparing antiemetic regimen to prevent chemotherapy-induced nausea and vomiting in patients with acute leukemia receiving multi-day intensive chemotherapy.

Olanzapine use for chemotherapy-induced nausea and vomiting (CINV) in hematological malignancies, for multi-day chemotherapy, and with a steroid-sparing antiemetic strategy is poorly understood. This study investigated if olanzapine is associated with improved prevention of CINV when added to a steroid-sparing antiemetic regimen in patients with acute leukemia receiving intensive, moderately emetogenic, multi-day chemotherapy. This was a single-center, retrospective cohort study in patients with acute leukemia. Patients who received olanzapine for CINV prevention were compared to those who did not. All patients received a 5-HT3 antagonist. Adult patients receiving moderately emetogenic, multi-day, intensive chemotherapy for acute leukemia were included. Patients were excluded if they received steroids greater than physiological doses during the study period. The primary endpoint was the complete response of CINV (no emesis or rescue antiemetic usage). This study included 58 patients, 12 patients received olanzapine and 46 patients were in the control group. Baseline demographics were similar. In the study population, 89.7% had acute myeloid leukemia, median age was 54 (interquartile range 42-63) years, 34.5% were female, 27.6% had prior CINV. Complete response of CINV was similar between groups, 4 (33.3%) and 15 (32.6%) patients in the olanzapine and control groups, respectively. Safety events were similar between groups. Patients with acute leukemia receiving multi-day intensive chemotherapy are at high risk for CINV. The limited data in this study suggests that olanzapine use within a steroid-sparing antiemetic regimen was well tolerated and associated with similar incidence and severity of CINV compared to the control group.

Efficacy and Safety of Olanzapine for the Prevention of Chemotherapy-induced Nausea and Vomiting in Children: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Chemotherapy-induced nausea and vomiting (CINV) remain the most distressing event in patients receiving highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC). This meta-analysis was conducted to evaluate the efficacy and safety of olanzapine containing regimen in preventing CINV in children on HEC and MEC. We searched PubMed, Embase, and Cochrane central register of controlled trials electronic databases to identify randomized clinical trials that compared 2 groups who either got olanzapine (olanzapine group) or placebo/no olanzapine (control group) for the prevention of CINV in children. The primary outcome was to determine the efficacy of olanzapine (complete response). The secondary outcomes were nausea control, the need for rescue medications, and adverse events of olanzapine. Three randomized clinical trials (n=394 patients) were included in this meta-analysis (olanzapine group, n=194, and placebo/control group, n=200). The pooled analysis of this meta-analysis found that olanzapine had a higher complete response in all phases of emesis in the HEC group and only in the acute phase in HEC/MEC groups compared with the control group. Olanzapine had higher nausea control in all phases of HEC but no nausea control in HEC/MEC. Olanzapine also reduced the need for rescue medications. A significant number of patients in the olanzapine group experienced somnolence (grades 1 and 2), but none of the participants discontinued the study due to side effects. In conclusion, this meta-analysis showed that olanzapine significantly prevented CINV in HEC. There was also a lesser need for rescue medications in the olanzapine group. Somnolence was higher in the olanzapine group, but it was clinically insignificant.

Olanzapine treatment effectively relieves breakthrough chemotherapy-induced nausea and vomiting: a real-world experience

BackgroundOlanzapine treatment prevents chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly emetogenic chemotherapy (HEC). However, its role in the secondary prevention of breakthrough CINV in real-world cancer care should be further evaluated.MethodWe conducted a retrospective study on patients receiving olanzapine to prevent breakthrough CINV refractory to standard antiemetic therapy. The major outcome was improvement in CINV, defined as any downgrade in CINV symptoms, according to the Common Terminology Criteria for Adverse Events. Comprete response was defined as no symptoms in CINV, i.e., Grade 0. These outcomes were compared in the HEC versus non-HEC groups and the standard- (5 or 10 mg/day) versus low- (2.5 mg/day) dose groups. The other outcome measurement was adverse events (AEs).ResultsWe analyzed 127 patients, including 92 women, with a median age of 50 years (range: 19–89 years). Baseline CINV severity was grade 1, 2, and 3 in 18%, 69%, and 13% of the patients, respectively. After prophylaxis with olanzapine at doses of 2.5, 5, or 10 mg/day, improvement was observed in 105 (83%) patients, with a complete response in 42 patients (33%). The improvement and complete remission rates for the HEC (n = 96) and non-HEC (n = 31) groups were 86% and 71% (p = 0.048) versus 38% and 19% (p = 0.062), respectively. The rates for the standard- (n = 98) and low- (n = 29) dose groups were 86% and 82% (p = 0.568) versus 28% and 52% (p = 0.015), respectively. Thirty-four patients (27%) experienced olanzapine-related AEs, mainly somnolence (n = 28). Grade 3 or higher AEs were not observed.ConclusionOur study results support the clinical application of olanzapine for the secondary prevention of breakthrough CINV.

The role of NEPA, a combination of netupitant and palonosetron, in the prevention of nausea and vomiting: case report and literature review

Chemotherapy-induced nausea and vomiting (CINV) is one of the most common complications of the systemic anticancer treatment. The manifestations of this complication are largely determined by subjective perceptions and individual characteristics of patients, but this complication may have unprecedented negative impact on the quality of life of cancer patients. There were significant advances in CINV prophylaxis in the recent decades, with many effective antiemetic drugs entering routine clinical practice. Current clinical guidelines for antiemetic therapy provide various possible strategies for CINV prevention, but do not give any specific guidance on the selection of individual agents within each class of emetogenic potential. NEPA, which is a fixed-dose combination of NK1-antagonist netupitant and 5-HT3 antagonist palonosteron, is the most recent antiemetic drug in clinical practice. This article reviews current data on the effectiveness of this drug and aims to define its “niche” in antiemetic therapy. The results of historical and most relevant studies demonstrating the effectiveness of NEPA in CINV prevention, pharmacological features of the drug and its potential advantages are discussed. The role of the drug in the existing therapeutic arsenal was evaluated using the example of a clinical report of treatment of a patient with an aggravated history (type 2 diabetes mellitus with poorly controlled hyperglycaemia) The patient achieved a complete response to the antiemetic therapy: no episodes of vomiting during treatment, the severity of nausea did not exceed the 1st grade, no additional prescription of antiemetic drugs was required.

Treatment of breakthrough and prevention of refractory chemotherapy-induced nausea and vomiting in pediatric cancer patients: Clinical practice guideline update.

This clinical practice guideline update provides recommendations for treating breakthrough chemotherapy-induced nausea and vomiting (CINV) and preventing refractory CINV in pediatric patients. Two systematic reviews of randomized controlled trials in adult and pediatric patients informed the recommendations. In patients with breakthrough CINV, escalation of antiemetic agents to those recommended for chemotherapy of the next higher level of emetogenic risk is strongly recommended. A similar recommendation to escalate therapy is made to prevent refractory CINV in patients who did not experience complete breakthrough CINV control and are receiving minimally or low emetogenic chemotherapy. A strong recommendation to use antiemetic agents that controlled breakthrough CINV for the prevention of refractory CINV is also made.

Fosnetupitant for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Short Review and Clinical Perspective.

Chemotherapy-induced nausea and vomiting (CINV) is often ranked by patients as one of the most distressing and feared consequences of chemotherapy. The novel neurokinin-1 (NK1) receptor antagonist fosnetupitant, a phosphorylated prodrug formulation of netupitant, was approved in Japan in 2022. Fosnetupitant is one of the standard treatments for the prevention of CINV in patients who are receiving highly (any treatment where CINV occurs in more than 90% of patients) or moderately (where CINV occurs in 30-90% of patients) emetogenic chemotherapies. The aim of this commentary is to describe the mechanism of action, tolerability, and antiemetic efficacy of single-agent fosnetupitant in the prevention of CINV, and to discuss its clinical application, in order to aid optimal use.

Effect of Mirtazapine for the Prevention of Nausea and Vomiting in Patients With Thoracic Cancer Receiving Platinum-based Chemotherapy.

Mirtazapine, which exerts an antagonistic effect on 5-hydroxytryptamine type 5-HT2A, 5-HT2C, 5-HT3 and H1 receptors, is considered useful for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). This study investigated the efficacy and safety of mirtazapine for the prevention of CINV in patients with thoracic cancer receiving platinum-based chemotherapy. A retrospective cohort study was conducted in patients with thoracic cancer receiving platinum-based chemotherapy with 15 mg mirtazapine once daily as a prophylactic antiemetic drug between January 2014 and December 2021. The effects of mirtazapine added to the standard antiemetic regimen for the prevention of CINV were evaluated in patients who had poor control of CINV in a preceding cycle and in patients who received the standard antiemetic therapy plus mirtazapine from their first cycle. A total of 35 patients were evaluated. Of these, 14 had poor control of CINV in a preceding cycle and received the standard antiemetic therapy plus mirtazapine in the next cycle. The rate of complete response in the delayed period in these patients was significantly improved from the preceding cycle to the next cycle (35.7% vs. 85.7%, p=0.018). In contrast, the other 21 patients had received the standard antiemetic regimen plus mirtazapine from the first cycle. The rate of complete response in the delayed period in these patients receiving the triplet antiemetic regimen plus mirtazapine as part of a cisplatin-based or carboplatin-based regimen and in patients receiving a doublet antiemetic regimen plus mirtazapine in a carboplatin-based regimen was 100%, 85.7% and 100%, respectively. No severe adverse events, including somnolence, were observed with the addition of mirtazapine. The addition of mirtazapine to the standard antiemetic regimen for CINV may be beneficial with acceptable safety when administered in association with platinum-based regimens to patients with thoracic cancer.

Addressing adherence to guidelines on prevention of acute chemotherapy-induced nausea and vomiting in pediatric patients.

Chemotherapy-induced nausea and vomiting (CINV) is a distressing adverse effect in children receiving cancer treatment. There are evidence-based pediatric clinical practice guidelines (CPG) on chemotherapy emetogenicity and acute CINV prevention, but adherence to these guidelines is low. A quality improvement-based study was conducted at McMaster Children's Hospital. The SMART aim was to increase adherence to guidelines on prevention of acute CINV in hospitalized patients receiving high (HEC) and moderately emetogenic chemotherapy (MEC) from baseline 25% to more than 70% by June 2021. Barriers were identified by process mapping, and a series of interventions were implemented. Guideline adherence was assessed in 270 inpatient chemotherapy administrations (HEC, MEC). Data were collected on 131 charts pre interventions and 139 charts post interventions. Interventions included education, addition of guideline-recommended anti-emetics to the inpatient formulary, and implementation of a standardized CPG tool. Initial rates of total CINV guideline adherence were 25%, which improved to 72% post intervention (p<.001). In subgroup analysis, guideline adherence in the MEC group improved from 13% to 34% (p=.015), and in the HEC group from 32% to 93% (p<.001). The most common reason for nonadherence in the HEC group was failure to use aprepitant as anti-emetic, and in MEC was option for ondansetron monotherapy prophylaxis. Using quality improvement methodology, barriers to guideline adherence were identified and interventions implemented. Guideline adherence for prevention of CINV improved, particularly in the HEC group but less for the MEC group. Future steps will include sustainability of interventions and addressing adherence in the MEC group.

The Effect and Safety of Olanzapine on Nausea and Vomiting in Children Receiving Moderately Emetogenic Chemotherapy.

In order to improve the complete recovery of nausea and vomiting, we conducted a study with the aim of preventing acute and delayed nausea and vomiting in children undergoing moderate emetogenic chemotherapy. A clinical trial study was done on 130 children received chemotherapy. Patients received olanzapine and placebo. All groups received granisetron along with dexamethasone (DEX). The severity of chemotherapy-induced nausea and vomiting (CINV) induced by chemotherapy was compared in two groups. The severity of nausea on the first, second, third, and fourth days was not significantly different (P > .05) in two groups. The number of patients without vomiting was significantly different during the first 24 hours after chemotherapy between patients in the two groups (82.3% vs 64.5%; P = .016). This study showed that olanzapine, which acts as an inhibitor of neurotransmitters, had a favorable efficacy in controlling acute and delayed CINV. More studies with large sample size are needed to compare the effect of olanzapine with other agents including aprepitant and palonosetron in the prevention of CINV.

A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of olanzapine plus triple antiemetic regimen for the prevention of multiday highly emetogenic chemotherapy-induced nausea and vomiting (OFFER study).

Evidence supports prophylactic use of olanzapine for the treatment of chemotherapy-induced nausea and vomiting (CINV). However, most studies to date have focused on patients with single-day highly emetogenic chemotherapy (HEC). Currently, administration of antiemetic therapies for nausea and vomiting induced by multiday chemotherapy regimens remains a challenge. In this study, we evaluated the efficacy of olanzapine combined with triple antiemetic therapy for the prevention of CINV in patients receiving multiday chemotherapy. We performed a randomized, double-blind, placebo-controlled phase 3 trial in 22 hospitals. Eligible patients were between 18 and 75 years old, were diagnosed with malignant solid tumors, and they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. All the study participants were scheduled to be treated with chemotherapy regimens containing 3-day cisplatin (3-day total dose ≥75mg/m2). Randomization was computer generated and stratified by gender and chemotherapy treatment history. Allocation was done via an interactive web response system. Enrolled patients were randomly assigned 1:1 to receive either 5mg olanzapine or placebo orally before bedtime for 5 days combined with intravenous fosaprepitant (150mg) 1h before the administration of cisplatin on day 1, ondansetron hydrochloride intravenously, and dexamethasone orally 30min before cisplatin from days 1 to 3. Dexamethasone was also administered at the same time on days 4 and 5. The primary endpoint was the proportion of subjects with complete response (no vomiting and no rescue therapy) within the overall phase (days 1-8) after starting chemotherapy. Baseline plasma concentrations of P-substance and 5-HT were measured for exploratory analysis. This study was registered at ClinicalTrials.gov, number NCT04536558. Between December 2020 and September 2021, 349 patients with malignant solid tumors were enrolled in the study, with 175 participants randomly assigned to receive olanzapine and 174 participants assigned to receive placebo. The proportion of patients who achieved a complete response in the overall phase was significantly higher in the olanzapine group than in the placebo group (69% vs. 58%, P=0.031). A complete response benefit was observed in the olanzapine group versus the placebo group in almost all the subgroups. Four factors were considered significantly associated with complete response in multivariable analysis: treatment group, gender, baseline plasma concentration of 5-HT, and prior radiotherapy. All the reported adverse events associated with olanzapine administration were grades 1 and2. Olanzapine (5mg) combined with fosaprepitant, ondansetron, and dexamethasone was better than triple antiemetic therapy alone for patients receiving multiday chemotherapy regimens. Based on these results, the four-drug combination should be recommended as the best antiemetic regimen given to patients receiving multiday cisplatin-based chemotherapy and baseline plasma concentration of 5-HT may be used to identify individuals who are prone to CINV. However, all these findings need to be further validated in future studies. Jiangsu Hansoh Pharmaceutical Group Co., Ltd. provided research grant and study drugs for this investigator-initiated study.