Prevention Of Chemotherapy-induced Nausea And Vomiting In Patients Research Articles

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.

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.

Aprepitant plus palonosetron versus dexamethasone plus palonosetron in preventing chemotherapy-induced nausea and vomiting in patients with moderate-emetogenic chemotherapy: A randomized, open-label, phase 3 trial.

SummaryBackgroundDespite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) by using dexamethasone combined with palonosetron for patients who received moderate-emetogenic chemotherapy (MEC), some of these patients still suffer from CINV. We evaluated whether aprepitant combined with palonosetron can improve the efficacy in the prevention of CINV in patients receiving MEC.MethodsThis was a single-centre, open-label, phase III, randomized controlled trial, which was done at the Sixth Affiliated Hospital of Sun Yat-sen University of China. The registered patients planned to receive mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) but had not received any chemotherapy previously. The patients were randomized in a 1:1 ratio to the aprepitant group (aprepitant 125 mg orally on day 1, 80 mg on day 2-3) and the dexamethasone group (dexamethasone 10 mg intravenously on day 1, 5 mg on days 2 and 3), both groups with palonosetron 0.25 mg intravenously on day 1. The primary endpoint was the proportion of patients who achieved a complete response (CR), defined as the absence of vomiting and no use of rescue medications in the overall phase (0–120 h). The primary outcome and safety were assessed in the modified intention-to-treat population, which excluded all patients who used estazolam within 24 h before registration and those who refused to keep a diary documenting the severity of nausea, frequency of vomiting, and the use of rescue therapy. This trial is registered with ClinicalTrials.gov, NCT02909478.FindingsBetween Sep 1, 2017, and Oct 23, 2019, 320 patients were enrolled, and 315 patients were evaluated. The proportion of patients who achieved CR was significantly higher with aprepitant than that noted with dexamethasone in the overall phase (88.8% vs. 74.2%; P = 0.0010; rate difference, RD 15%, 95% CI, 6% to 23%) and in the delayed phase (25–120 h), 90.6% vs. 75.5%, (P < 0.0001; RD 15%, 95%CI, 7% to 23%). No significant difference of CR rate was observed in the acute phase (0–24 h), 93.8% vs. 93.5%, (P = 0.94; RD 0%, 95% CI, -5% to 6%)). In the overall phase, the incidence of insomnia (P < 0.0010), dyspepsia (P = 0.038), and flushing (P = 0.0010) reported by the patients was significantly higher in the dexamethasone group than that in the aprepitant group.InterpretationAprepitant combined with palonosetron is superior to dexamethasone combined with palonosetron in patients who received the MEC regimen mFOLFOX6 in terms of preventing CINV.FundingThe National Key R&D Program of China (2019YFC1316000) and the National Natural Science Foundation of China (81974369).

POSA159 Cost-Effectiveness of Netupitant/Palonosetron in the Treatment of Chemotherapy-Induced Nausea and Vomiting in the UK

Chemotherapy-induced nausea and vomiting (CINV) is among the most common side-effects reported by cancer patients undergoing chemotherapy. This analysis aimed to evaluate the cost-effectiveness of fixed-combination netupitant/palonosetron (NEPA) compared with other commonly used antiemetic treatments for the prevention of CINV in patients undergoing highly emetogenic chemotherapy (HEC) in the UK.

English

BACKGROUND Chemotherapy-induced nausea and vomiting (CINV) is a frequent and feared adverse effect of cancer chemotherapy. International guidelines recommend combinations of 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists, dexamethasone, and/or neurokinin-1 (NK1) receptor antagonists for the control of CINV in patients receiving highly emetogenic chemotherapy (HEC) as a part of their treatment. Even though, nausea in delayed period is less controlled and poses a major concern for these patients. METHODS This open label, prospective study was conducted in a rural medical college in Etawah District in Uttar Pradesh, India from November 2017 to November 2018 over a period of 1 year to observe the efficacy of low dose (5 mg OD) olanzapine in combination with standard anti-emetic regimen for the prevention of CINV. Olanzapine is a food and drug administration (FDA) approved antipsychotic drug that has anti-emetic activity and has shown to improve CINV. Low dose olanzapine along with a standard combination of ondansetron, dexamethasone and aprepitant was given to patients receiving highly emetogenic chemotherapy (Cisplatin &gt;70 mg/m2 or doxorubicin-cyclophosphamide combination). CINV was assessed using common toxicity criteria of adverse events (CTCAE) version 5.0. RESULTS Complete response to nausea was observed in 90.90 %, 60.60 % and 54.54 % in acute, delayed and overall period respectively. Complete response to vomiting was observed in 96.96 %, 69.69 % and 66.66 % in acute, delayed and overall period respectively. Complete response to Grade-2 (or above) nausea was observed in 96.96 %, 93.93 % and 90.90 % in acute, delayed and overall period, respectively. Daytime Grade -3 somnolence which was seen in 2/33 patients (6.06 %) was attributable to olanzapine. Patients receiving olanzapine were more likely to have complete response of nausea and emesis in the early, late, and overall assessment periods especially of higher grade (G2 and G3). CONCLUSIONS The authors concluded that low dose olanzapine 5 mg OD combined with an NK1- receptor antagonist, a 5-HT3–receptor antagonist, and dexamethasone is safe and efficacious in the prevention of CINV in patients receiving HEC. KEYWORDS Olanzapine, Low Dose, CINV, HEC

Prevention of chemotherapy-induced nausea and vomiting in the real-world setting in Spain

PurposeProper monitoring and management of chemotherapy-induced nausea and vomiting (CINV) with antiemetics is crucial for cancer patients. This study aimed to evaluate the use of antiemetics for the treatment of highly emetogenic chemotherapy (HEC) including carboplatin in the real-world setting in Spain.MethodsA representative panel of cancer specialists was asked to collect information about the antiemetic treatments provided to patients receiving chemotherapy. Records formed part of the Global Oncology Monitor© database (Ipsos Healthcare, London, UK). Chemotherapy data were extrapolated using Ipsos Healthcare’s projection methodology.ResultsA total of 73 experts were finally included. Data from 9519 patients, estimated to be representative of 202,084 patients, were collected. HEC (and carboplatin-based chemotherapy) was administered to 73,118 (36%) patients, cisplatin-based therapy being the most frequent treatment (n = 34,649, 47.38%). Neurokinin-1 receptor antagonists (NK1RAs) alone or in combination were used as prophylaxis for CINV in 14,762 (20%) patients, while the combination of NK1RA with 5-hydroxytryptamine-3 receptor antagonist (5-HT3RAs) and dexamethasone as recommended by the international guidelines was used in 5849 (8%) patients only. No antiemetic prophylaxis was administered to 8.46% of the patients receiving HEC (n = 6189). Physicians classified cisplatin-, anthracycline-cyclophosphamide (AC-), and carboplatin-based regimens as HEC in 63%, 22% and 4% of the cases, respectively.ConclusionsThe use of NK1RA-containing regimens for CINV prevention in patients treated with HEC was less than expected, suggesting poor adherence to international antiemetic guidelines.

Antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting: An updated systematic review and meta-analysis.

To systematically evaluate the efficacy and safety of antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) and provide updated information for clinical practice. Pubmed, Embase, the Cochrane Library, and 3 Chinese literature databases were systematically searched. Randomized controlled trials comparing standard regimen (5-hydroxytryptamine-3 receptor antagonist and glucocorticoid) with aprepitant triple regimen (aprepitant plus the standard regimen) for preventing CINV were screened. Literature selection, data extraction, and quality evaluation were performed by 2 reviewers independently. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the meta-analysis using RevMan 5.3 software. A total of 51 randomized controlled trials were finally included in the systematic review. Compared with the standard regimen, the aprepitant triple regimen significantly improved the complete response in the overall (OR 1.88, 95% CI 1.71-2.07), acute (OR 1.96, 95% CI 1.65-2.32) and delayed (OR 1.96, 95% CI 1.70-2.27) phases, regardless of emetogenic risk of chemotherapy. Aprepitant could also significantly enhance the proportions of patients who have no emesis, nausea, or use of rescue medication respectively in the overall, acute and/or delayed phases. Aprepitant was found to be associated with decreased risk of constipation (OR 0.85, 95% CI 0.74-0.97), but increased the incidence of hiccup (OR 1.26, 95% CI 1.05, 1.51). There were no statistically significant differences between the 2 groups on other safety outcomes. The aprepitant triple regimen is effective for the prevention of CINV in patients being treated with moderately or highly emetogenic chemotherapy, and has a significant tendency to reduce the risk of constipation and increase the incidence of hiccup.

Cost effectiveness analysis of additional NK-1 receptor antagonist to olanzapine, ondansetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin.

e19398 Background: NK-1 receptor antagonist (NK1RA) is a standard anti-emetic agent in chemotherapy-induced nausea and vomiting (CINV) prevention in patients receiving high-dose (HD) cisplatin. However, in limited-resource settings, three-drug regimen including olanzapine, ondansetron and dexamethasone is affordable and effective in CINV prevention in these patients. Objectives: To evaluate cost effectiveness of additional NK1RA for CINV prevention in Thai patients receiving HD cisplatin in 3-cycle horizon, societal perspective. Methods: During January to December 2019, 20 patient receiving HD cisplatin were prospectively enrolled to receive standard three-drug regimen at King Chulalongkorn Memorial Hospital. Total medical resource utility, non-medical cost and clinical outcomes were actually collected and used for establishing decisional-tree model and cost-effectiveness analysis. Three arms decisional-tree model was constructed. First, standard strategy, a real-world practice in Thailand, patients received three-drug regimen in all cycles of chemotherapy. Second, NK1RA-rescue strategy, patients received three-drug regimen in the first cycle and additional NK1RA in subsequent cycles if the patients experienced CINV. Third, NK1RA upfront strategy, patients received four drug NK1RA-containing regimen in all cycles. Complete response (CR) rate was assumed to be 92.5% in NK1RA-containing regimen based on clinical trials. The study endpoint is to compare cost and QALYs in term of incremental cost-effectiveness ratio (ICER). Results: CR rates were 90% and 71% in first and second cycle in patients receiving standard regimen. The NK1RA upfront strategy produced greatest QALYs of 0.0351, followed by 0.0328 and 0.0292 in NK1RA-rescue strategy and standard strategy respectively. Mean total costs were 10420.46, 3332.19 and 2841.30 Thai baht (THB) respectively. The ICER of NK1RA-rescue strategy relative to standard strategy was 135,774 THB per QALY and the ICER of NK1RA upfront strategy relative to NK1RA-rescue strategy was 3,096,654 THB per QALY. Therefore, the ICER of NK1RA-rescue strategy but not NK1RA upfront strategy is considered to be cost effective at the willingness-to-pay level of 160,000 THB per QALY. Conclusions: Our findings suggested that the additional NK1RA as a rescue strategy is cost-effective in patients receiving HD cisplatin in Thai health care.

Abstract P2-12-04: Efficacy of intravenous (IV) NEPA and oral NEPA, fixed NK1/5-HT3 receptor antagonist (RA) combination agents, for prevention of chemotherapy-induced nausea and vomiting (CINV) following anthracycline-cyclophosphamide (AC)-based chemotherapy

Abstract Background: The antiemetic guideline-based standard of care for prevention of CINV in patients receiving AC-based chemotherapy is the combination of an NK1 RA, a 5-HT3 RA, and dexamethasone (DEX). An IV formulation of NEPA (fixed combination of the NK1 RA, fosnetupitant and 5-HT3 RA, palonosetron) was recently approved in the United States. Two studies were completed in patients receiving cisplatin (Phase 3) or AC (Phase 3b) to assess the safety of IV NEPA, with specific attention paid to injection-site/hypersensitivity reactions as such events have occurred with other NK1 RAs, particularly in the AC setting. No treatment-related injection-site reactions were reported in &amp;gt;1300 infusions of IV NEPA. Oral NEPA was previously shown to be superior to palonosetron in a Phase 3 AC study. This analysis presents the efficacy data of IV NEPA and oral NEPA in the AC setting. Methods: Data is compiled from the IV NEPA Phase 3b study as well as from an oral NEPA registration study in females with breast cancer undergoing AC-based chemotherapy. IV NEPA was administered as a single 30-minute infusion and oral NEPA was given as a single capsule 60 minutes prior to AC. Patients also received DEX prior to AC on Day 1 only. Complete response (CR: no emesis/no rescue medication) rates are summarized for the acute (Day 1), delayed (Days 2-5) and overall (Days 1-5) phases of Cycle 1 for each treatment/study and also pooled for oral NEPA across the 2 studies. No formal statistical comparisons were performed. Results: Patient characteristics were similar in both studies. CR rates were comparable for IV NEPA and oral NEPA in the individual studies as well as with oral NEPA when pooled across the 2 studies (Table). Cycle 1 Complete Response IV NEPA StudyOral NEPA Study Pooled Studies % Patients IV NEPAOral NEPAOral NEPAOral NEPA(N = 200)(N = 202)(N = 708)(N = 910)Acute (0-24 h)86.588.688.388.4Delayed (25-120 h)75.578.776.476.9Overall (0-120 h)73.077.273.974.6 Conclusions: Both IV and oral formulations of NEPA in combination with DEX represent guideline-compliant single-dose antiemetic agents that are highly effective over 5 days in patients receiving AC-based chemotherapy. Citation Format: Matti Aapro, Lee Schwartzberg. Efficacy of intravenous (IV) NEPA and oral NEPA, fixed NK1/5-HT3 receptor antagonist (RA) combination agents, for prevention of chemotherapy-induced nausea and vomiting (CINV) following anthracycline-cyclophosphamide (AC)-based chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-04.

A randomized, double-blind, placebo-controlled phase III trial evaluating olanzapine 5 mg combined with standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy: J-FORCE Study.

11503 Background: Olanzapine (OLZ) 10 mg added to standard antiemetic therapy including aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) has been recommended for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy (HEC). Guidelines suggest that a dose of 5 mg should be taken into consideration in patients at risk of sedation. OLZ 5 mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate OLZ 5 mg in addition to standard antiemetic therapy for the prevention of CINV in patients receiving cisplatin-based chemotherapy. Methods: Patients receiving cisplatin (≥ 50 mg/m2) were randomly assigned to either OLZ 5 mg or placebo on days 1–4, combined with APR, PALO and DEX. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120 h). A total of 690 patients were required to detect a 10% increase in CR from 65% in the placebo to 75% in the OLZ, with a one-sided alpha of 2.5% and a power of 80%. Results: A total of 710 patients were enrolled (OLZ 356 and placebo 354). CR in the delayed phase was 79.1% (95% CI: 74.9–83.3) in the OLZ 5 mg and 65.8% (95% CI: 60.9–70.8) in the placebo ( p &lt; 0.001). Other efficacy results are summarized in Table. The most common treatment-related adverse events was somnolence (43.1% for OLZ vs. 33.0% for placebo). Conclusions: OLZ 5 mg combined with APR, PALO and DEX can be considered a new standard antiemetic therapy in patients receiving cisplatin-based chemotherapy. Clinical trial information: UMIN000024676. [Table: see text]

OLANZAPINE FOR THE PREVENTION AND TREATMENT OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING

Chemotherapy-induced nausea and vomiting (CINV) has tremendous negative impact on daily life of cancer patients and their quality of life. In this article we analyzed current clinical guidelines in preventive measures and treatment of CINV as well as efficacy of recommended standard regimens for CINV prevention in patients receiving high emetogenic chemotherapy (HEC). We summarized existing data about olanzapine – affordable antipsychotic agent with potent antiemetogenic activity which is quite useful for CINV prophylaxis in patients receiving HEC. We highlighted possible future directions for research of olanzapine in oncology and reasons that preclude integration of this drug in routine clinical practice in Russia.

Cost-effectiveness analysis of olanzapine-containing antiemetic therapy for managing highly emetogenic chemotherapy in Southeast Asia: a multinational study.

Recent studies suggested that olanzapine, together with dexamethasone and serotonin-3 receptor antagonist (5HT3RA), is effective in preventing chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC). This regimen is particularly useful in Southeast Asia (SEA) countries where resources are limited. We aimed to evaluate the cost-effectiveness of incorporating olanzapine into standard antiemetic regimens for the prevention of CINV in patients receiving HEC among SEA countries. Using a decision tree model, clinical and economic outcomes associated with olanzapine-containing regimen and standard antiemetic regimen (doublet antiemetic regimen: dexamethasone+first generation 5HT3RA) in most SEA countries except in Singapore (triplet antiemetic regimen: dexamethasone+first generation 5HT3RA + aprepitant) for CINV prevention following HEC were evaluated. This analysis was performed in Thailand, Malaysia, Indonesia, and Singapore, using societal perspective method with 5-day time horizon. Input parameters were derived from literature, network meta-analysis, government documents, and hospital databases. Outcomes were incremental cost-effectiveness ratio (ICER) in USD/quality-adjusted life year (QALY) gained. A series of sensitivity analyses including probabilistic sensitivity analysis were also performed. Compared to doublet antiemetic regimen, addition of olanzapine resulted in incremental QALY of 0.0022-0.0026 with cost saving of USD 2.98, USD 27.71, and USD 52.20 in Thailand, Malaysia, and Indonesia, respectively. Compared to triplet antiemetic regimen, switching aprepitant to olanzapine yields additional 0.0005 QALY with cost saving of USD 60.91 in Singapore. The probability of being cost-effective at a cost-effectiveness threshold of 1 GDP/capita varies from 14.7 to 85.2% across countries. The use of olanzapine as part of standard antiemetic regimen is cost-effective for the prevention of CINV in patients receiving HEC in multiple SEA countries.

Olanzapine as antiemetic drug in oncology: a retrospective study in non-responders to standard antiemetic therapy

Background The role of olanzapine in the treatment of chemotherapy-induced nausea and vomiting (CINV) in addition to the antiemetic therapeutic combination with aprepitant, setrons, and corticosteroids has not been well defined. Objective To investigate the effectiveness of the addition of olanzapine to a standard triplet therapy for the prevention of CINV in patients who experienced CINV during their first chemotherapy course, despite receiving a well-managed prevention protocol. Setting One comprehensive cancer centre in France. Method In a retrospective study with comparator, patients with a high risk of emesis were assigned to two groups during two different 6-month periods, before and after the introduction of olanzapine in clinical practice, respectively. In the olanzapine group, the antiemetic protocol for the second course of chemotherapy was reinforced by the addition of olanzapine at 5mg/day from day 1 to 5 in contrast with the control group. Main outcome measure The proportion of patients who experienced neither nausea nor emesis during the delayed phase (24-120h). Results The 25 patients in each group exhibited comparable characteristics and emetic chemotherapy level. During the first course, no significant difference was observed. During the second course, nausea and vomiting were ameliorated in 12 patients in the olanzapine group and 4 patients in the control group (p < 0.05). Nausea (12 vs. 4, p < 0.05) and vomiting (18 vs. 11, p < 0.05) also significantly improved. In the OLZ group, no adverse event was linked to olanzapine use. Conclusion The addition of olanzapine was observed to effectively restore CINV prevention in patients who did not respond to standard antiemetic therapy.

Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy.

BackgroundChemotherapy-induced nausea and vomiting (CINV) is a major adverse toxicity of cancer chemotherapy. Recommended treatments for prevention of CINV vary among published guidelines, and optimal care for CINV caused by moderately emetogenic chemotherapy has not been established. This study assessed the efficacy and safety of triple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant for carboplatin-based chemotherapy. Chemotherapy-naïve patients with lung cancer scheduled for a first course of a carboplatin-containing regimen formed the study cohort. Patients were pretreated with antiemetic therapy comprising palonosetron (0.75 mg, i.v.) and dexamethasone (9.9 mg, i.v.) on day 1, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. Primary endpoint was the proportion of patients who did not experience vomiting and did not require rescue medication [complete response (CR)] in the acute phase (0–24 h), late phase (24–168 h) and overall. Secondary endpoint was the proportion of patients who experienced no vomiting episodes and no more than mild nausea without the need for rescue medication [complete control (CC)].ResultsPrevalence of a CR during the acute phase, delayed phase, and overall was 100, 91.9 and 91.9%, whereas that of CC was 100, 84.4 and 84.4%, respectively. The most common adverse event was mild constipation; severe adverse events related to antiemetic treatment were not observed.ConclusionTriple antiemetic therapy comprising palonosetron, dexamethasone and aprepitant shows excellent effects in the prevention of CINV in patients receiving a carboplatin-containing regimen.

Disparities in the availability of and access to antiemetics recommended by the international antiemetic guidelines in Serbia, Japan, and Nepal.

117 Background: Guideline-consistent antiemetic therapy requires 4 classes of antiemetics (AEs) to be available and accessible for the optimal prevention of chemotherapy induced nausea and vomiting (CINV): serotonin3 receptor antagonists (5HT3RAs), neurokinin 1 receptor antagonists (NK1RAs), dopamine receptor antagonists (DOPRAs) and dexamethasone. To evaluate disparities in the availability and accessibility of AEs recommended by the international antiemetic guidelines for the prevention of CINV inpatients treated in governmental hospitals in Nepal (low), Serbia (upper-middle) and Japan (high-income). Methods: Availability was evaluated by the formulary availability and marketing authorization (MA) in Serbia (RS), Japan (JP) and Nepal (NP). Accessibility was assessed by the National Health Insurance Fund (NHIF) coverage in Serbia and Japan and by the affordability in Nepal. Off-label use of medications is not legitimate in Serbia and Japan. Results: Barriers are presented in Table. Serbia has no access to NK1RAs and palonosetron for the prevention of CINV after HEC-AC and carboplatin. There are no barriers in Japan to provide all 4 classes of AEs. In Nepal all AEs are payed out of pocket and the guideline implementation completely depends on the affordability. Olanzapine is accessible in Nepal, but not in Japan and Serbia due to restricted off-label use of medications. Conclusions: The real life implementation of antiemetic guidelines for the prevention of CINV in various countries depends on the availability of and access to AEs recommended by the guideline. Identified barriers in Serbia and Nepal preclude physicians from providing optimal supportive care. [Table: see text]

Ramosetron Versus Ondansetron in Combination With Aprepitant and Dexamethasone for the Prevention of Highly Emetogenic Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Randomized Phase III Trial, KCSG PC10-21.

A combination of serotonin receptor (5-hydroxytryptamine receptor type 3) antagonists, NK-1 receptor antagonist, and steroid improves the complete response (CR) of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Ramosetron's efficacy in this triple combination regimen has not been investigated. This prospective, multicenter, single-blind, randomized, phase III study compares a combination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic CINV. Aprepitant and dexamethasone were orally administered for both arms. Ramosetron and ondansetron were intravenously given to the RAD and OAD groups. The primary endpoint was no vomiting and retching and no need for rescue medication during the acute period (day 1); the noninferiority margin was -15%. A total of 299 modified intention-to-treat cancer patients who received RAD (144 patients) and OAD (155 patients) were eligible for the efficacy analysis. The CR rates of RAD versus OAD were 97.2% versus 93.6% during the acute period, 77.8% versus 73.6% during the delayed period (day 2-5), and 77.1% versus 71.6% during the overall period. Furthermore, RAD was noninferior to OAD in subgroups stratified by age, cancer type, chemotherapeutic agents, and schedule. Repeated measures analysis showed that in male patients, RAD was superior to OAD. Profiles of adverse events were similar in both groups. RAD is as effective and tolerable as OAD for CINV prevention in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered one of the best partners for aprepitant.

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) over multiple cycles of highly or moderately emetogenic chemotherapy (HEC, MEC).

210 Background: The long-acting neurokinin-1 receptor antagonist (NK-1 RA) rolapitant has demonstrated efficacy for CINV prevention in patients receiving HEC and MEC during Cycle 1. The efficacy and safety of rolapitant was examined during subsequent cycles 2–6 in a pooled analysis. Methods: In 4 double-blind, active-controlled studies, patients were randomized to oral rolapitant 180 mg or placebo 1–2 hours before chemotherapy. All patients received active control: 5HT3 receptor antagonist + oral dexamethasone. Patients completing Cycle 1 could receive the same anti-emetic treatment in subsequent cycles. On Days 6-8 of subsequent cycles, patients self-reported the incidence of emesis, or of nausea interfering with normal daily life following Day 1 of chemotherapy. Results: A greater proportion of patients on rolapitant than on active control reported no emesis or interfering nausea separately for each subsequent cycle. Results of individual studies and pooled analysis are shown in the Table. During cycles 2-6, the incidence of treatment-related adverse events (AEs) was similar for rolapitant (5.5%) and control (6.8%). The most common treatment-related AEs were similar in both arms: constipation (rolapitant: 1.2%; control: 0.8%) and fatigue (rolapitant: 1.3%; control: 1.8%). Conclusions: Rolapitant was superior to active control in reducing CINV when administered over multiple cycles of moderately or highly emetogenic chemotherapy, with no increase in toxicity. Clinical trial information: NCT00394966 - NCT01500213 - NCT01500226 - NCT01499849. [Table: see text]

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in non–anthracycline/cyclophosphamide (AC)-based moderately emetogenic therapy (MEC).

209 Background: Rolapitant, a novel NK-1 receptor antagonist, showed efficacy in CINV prevention in patients (pts) receiving MEC (anthracycline/cyclophosphamide (AC) and other regimens) in a global phase 3 trial. Recent anti-emetic guidelines consider AC based regimens to be highly emetogenic. In this post hoc analysis, the efficacy and safety of rolapitant was assessed in Cycle 1 in pts receiving non-AC MEC, and in the subset of pts receiving carboplatin-based MEC. Methods: In a double-blind, active-controlled study, pts were randomized to oral rolapitant 180 mg or placebo 1–2 hours before MEC. All pts received granisetron 2 mg oral on days 1-3 and oral dexamethasone 20 mg on day 1. Complete response (CR = no emesis + no use of rescue medication), no emesis, and no nausea were assessed in overall (0-120 h), acute (0-24 h), and delayed ( &gt; 24-120 h) phases. Results: CR was significantly (P &lt; 0.01) higher with rolapitant than active control in overall and delayed phases in the carboplatin subset and in all 3 phases in the non-AC population (Table). No emesis rates were significantly (p &lt; 0.05) higher with rolapitant in the carboplatin subset in the overall phase. No nausea rates were significantly (P &lt; 0.05) higher with rolapitant in the overall and delayed phases in carboplatin-based MEC. Incidences of treatment-related AEs in Cycle 1 with rolapitant vs. active control were 11.3% vs. 6.7% in the carboplatin-based subset. Most common AEs with rolapitant and active control were constipation, fatigue, and headache. Conclusions: Rolapitant was superior to active control in preventing CINV in pts receiving non-AC MEC, including in the subgroup receiving carboplatin. Rolapitant was well tolerated with low incidence of AEs. Clinical trial information: NCT01500226. [Table: see text]

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in moderately emetogenic therapy (MEC).

9622 Background: Rolapitant, a novel NK-1 receptor antagonist, showed efficacy for prevention of CINV in patients (pts) receiving MEC (anthracycline/cyclophosphamide (A/C) and other regimens) in a ...