Prevention Of Chemotherapy-induced Nausea And Vomiting Research Articles

Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting in lung cancer patients receiving carboplatin-based therapies.

e21685 Background: Chemotherapy-induced nausea and vomiting (CINV) is a distressing symptom of cancer treatment; in lung cancer, carboplatin is commonly used. In a post hoc analysis, we explored prevention of CINV in lung cancer patients with a single-day triple-antiemetic fosaprepitant (FA) regimen compared with a standard 3-day control regimen. Methods: This was a phase 3, global, randomized, double-blind, parallel-group study in adults scheduled to receive an intravenous (IV) dose of ≥1 moderately emetogenic chemotherapy (MEC) on treatment day 1 (NCT01594749). Subjects were randomly assigned 1:1 to a control or FA regimen. The control regimen consisted of 8 mg oral ondansetron, 20 mg dexamethasone, and IV saline as placebo before the first dose of MEC on day 1, and 8 mg oral ondansetron 8 hours after the first dose and every 12 hours on days 2 and 3. The FA regimen consisted of the same dose of oral ondansetron on day 1, along with 12 mg dexamethasone and a single dose of 150 mg IV FA before the first dose of MEC on day 1, with no additional prophylactic antiemetic beyond day 1. The primary end point was complete response (CR; no vomiting or rescue medication) in the delayed phase (25-120 hours). Results: Overall, 1000 subjects were included in the intention-to-treat population (FA: n = 502; control: n = 498). The primary end point was met ( P < 0.001; FA vs control). In a subset of 254 subjects with lung cancer (71% male), 129 in FA regimen and 125 in control regimen, most (98%) received carboplatin-based chemotherapy. CR in the delayed phase was achieved by 80.6% in the FA group and 74.4% in the control group (difference, 6.2%). More subjects had no vomiting episodes in the FA (85.3%) vs control (78.4%) groups within the delayed phase (difference, 6.9%), and overall time-to-first vomiting episode was longer for subjects in the FA group. Adverse events (AEs) were similar between groups: overall AEs occurred in 57.7% and 54.8%, and serious AEs occurred in 12.3% and 12.1% in the FA and control groups, respectively. No serious AEs were considered related to study medication. Conclusions: A single-day IV FA regimen is effective for preventing CINV in patients with lung cancer receiving carboplatin. Clinical trial information: NCT01594749.

Phase III study of NEPA, a fixed combination of netupitant and palonosetron, versus an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV).

10090 Background: Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize CINV control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a novel fixed combination of a highly selective NK1 receptor antagonist (RA), netupitant (300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3RA, has shown superior CINV prevention compared to PALO in cisplatin and AC-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen, with the primary objective being to demonstrate non-inferiority in preventing CINV. Methods: This randomized, double-blind, parallel group Phase III study conducted in an Asian population was designed to compare efficacy and safety of a single oral dose of NEPA with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at -10%. Secondary efficacy endpoints included no emesis and no significant nausea (NSN: < 25mm on 100mm VAS). Results: Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR; no emesis and NSN rates favored NEPA. Most frequent study drug-related adverse events (AEs) for NEPA included constipation (8.0%) and hiccups (2.7%). The type/incidence/severity of AEs were similar for NEPA and APR/GRAN. Conclusions: In this first study comparing NK1RA regimens and 4 days of DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC. [Table: see text]

Possible mechanisms of serotonin and aprepitant actions in chemotherapy induced nausea and vomiting (CINV): Insights into the mechanisms of serotonin and aprepitant actions in CINV—According to recent multi-institutional double-blind randomized clinical research on the AC regimen.

6587 Background: One of our interests has been whether palonosetron(P) would be superior to granisetron(G) when administering triplet antiemetic therapy for the prevention of CINV, since a prior trial demonstrated P to be superior to G for controlling CINV induced by highly emetogenic chemotherapy (HEC) in doublet therapy. In this study(TTT; trial for antiemetic therapy), we assessed the efficacies of P and G for use as triplet antiemetic therapy for AC, by monitoring CINV, focusing complete response (CR; no vomiting and no rescue medicine) in the delayed phase. The primary endpoint of TTT was a CR during the delayed phase with 5-HT3ra plus dexamethasone and aprepitant administration for AC. The purpose of gaining insights into the possible mechanism of action of aprepitant and P was to obtain ideas for the next strategy against CINV. Methods: Between 2012 and 2015, 491 breast cancer receiving AC were recruited from 11 institutions, and randomly assigned to either single-dose P(0.75mg) or G(40μg/kg) prior to AC on day 1, both with dexamethasone (9.9 mg) and aprepitant (125mg) on day 1 followed by additional doses (80mg) on days 2 and 3. Age, institution and habitual alcohol intake were used as stratification factors. The primary endpoint was a CR. Results: All 491 patients were included in efficacy analyses: 246 patients in the group P and 245 in the group G. The difference in CR during the delayed phase, i.e. 24 hrs after the administration of AC, did not reach statistical significance, however, there was a remarkable difference between 48 and 72 hrs in the day-to-day analysis(p < 0.02). Conclusions: P showed better efficacy in controlling CINV between 48 to 72 hours after AC, than G as triplet antiemetic therapy for AC. We can reasonably speculate that the influence of serotonin has two peaks (0-24 hrs and 48-72 hrs). For controlling CINV in the delayed phase, not only an NK1 receptor antagonist but also administering a 5-HT3ra with long life should be considered until 72 hrs after HEC. Clinical trial information: UMIN 000007882.

Efficacy of olanzapine for prevention of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis.

e21692 Background: Olanzapine is an atypical antipsychotic medication which has shown efficacy in prevention of chemotherapy-induced nausea and vomiting (CINV) in multiple trials. This study aims to investigate the efficacy of Olanzapine to prevent CINV with an up-to-date systematic review and meta-analysis. Methods: A literature search of Ovid MEDLINE, Embase and Cochrane library was performed to identify randomized controlled trials of olanzapine compared to other antiemetic therapy (5HT3 and/or NK1 antagonist with or without steroids) for prevention of CINV in patients age >=18 years up until December 2016. The primary endpoint was no emesis or nausea episodes in acute (0-24hrs), delayed (24-120hrs) and overall (0-120hrs) period in patients receiving highly or moderately emetogenic chemotherapy (HEC or MEC). Statistical analysis was performed using Review Manager (RevMan 5.3). The Mantel–Haenszel method was applied and random effect analysis model was used to calculate risk ratios. Results: From the literature, 12 RCTs met the inclusion criteria. The age range of patients was 18-89 years. Seven trials included only patients who received HEC while 5 trials included patients receiving either HEC or MEC in various proportions. Olanzapine was statistically superior for 5 primary endpoints except for no nausea in acute period (Table 1). In the non-steroids cohort, olanzapine was superior for no emesis in all 3 periods but statistically significant only for delayed period. Conclusions: Olanzapine is superior to other antiemetic therapy for prevention of CINV. It is less expensive and can improve patient’s quality of life and chemotherapy adherence. [Table: see text]

APF530 versus ondansetron, each in a guideline-recommended three-drug regimen, for the prevention of chemotherapy-induced nausea and vomiting due to anthracycline plus cyclophosphamide-based highly emetogenic chemotherapy regimens: a post hoc subgroup analysis of the Phase III randomized MAGIC trial.

BackgroundAPF530, a novel extended-release granisetron injection, was superior to ondansetron in a guideline-recommended three-drug regimen in preventing delayed-phase chemotherapy-induced nausea and vomiting (CINV) among patients receiving highly emetogenic chemotherapy (HEC) in the double-blind Phase III Modified Absorption of Granisetron In the prevention of CINV (MAGIC) trial.Patients and methodsThis MAGIC post hoc analysis evaluated CINV prevention efficacy and safety of APF530 versus ondansetron, each with fosaprepitant and dexamethasone, in patient subgroup receiving an anthracycline plus cyclophosphamide (AC) regimen. Patients were randomized 1:1 to APF530 500 mg subcutaneously (granisetron 10 mg) or ondansetron 0.15 mg/kg intravenously (IV) (≤16 mg); stratification was by planned cisplatin ≥50 mg/m2 (yes/no). Patients were to receive fosaprepitant 150 mg IV and dexamethasone 12 mg IV on day 1, then dexamethasone 8 mg orally once daily on day 2 and twice daily on days 3 and 4. Patients were mostly younger females (APF530 arm, mean age 54.1 years, female, 99.3%; ondansetron arm, 53.8 years, female 98.3%). The primary end point was delayed-phase (>24–120 hours) complete response (CR).ResultsAPF530 versus ondansetron regimens achieved numerically better CINV control in delayed and overall (0–120 hours) phases for CR, complete control, total response, rescue medication use, and proportion with no nausea. APF530 trends are consistent with the overall population, although not statistically superior given the underpowered AC subgroup analysis. The APF530 regimen in this population was generally well tolerated, with safety comparable to that of the overall population.ConclusionAPF530 plus fosaprepitant and dexamethasone effectively prevented CINV among patients receiving AC-based HEC, a large subgroup in whom CINV control has traditionally been challenging.

Management of Chemotherapy-Induced Nausea and Vomiting in Pediatric Patients.

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life and is perceived by patients as a major adverse effect of the treatment. This review summarizes the safety and efficacy of current antiemetic agents for the prevention of CINV in children. Information on antiemetic prophylaxis for CINV in children was obtained from a literature review of current peer-reviewed articles and recent international guidelines. The literature review and the international antiemetic guidelines provide recommendations for use of specific antiemetics in children based on the emetogenicity of the chemotherapy. 5-Hydroxytryptamine-3 (5-HT3) receptor antagonists have been safe and effective in the prevention of acute emesis with a few patients experiencing mild headache. No adequate studies have been conducted to date for specific recommendations for the prevention of delayed nausea and vomiting in children. The neurokinin (NK)-1 receptor antagonist aprepitant has been approved by the US FDA for use in children of a specific age and weight. No studies for the NK1 receptor antagonists netupitant and rolapitant in children have been conducted. Olanzapine, an antipsychotic, has been shown to be safe and effective in preventing nausea and emesis in adult patients receiving chemotherapy. Its use in children has been limited to children with poor control of CINV; more studies are necessary in this population. In conclusion, practitioners should follow international antiemetic guidelines to provide patients with the specific antiemetics in the recommended dose for the highest possible quality of care.

New options and controversies in the management of chemotherapy-induced nausea and vomiting

An expanding array of options for prevention and treatment of chemotherapy-induced nausea and vomiting (CINV), including regimens containing olanzapine or recently approved neurokinin 1 (NK1) receptor antagonists, are reviewed. Up to 80% of patients receiving chemotherapy have CINV. Current practice guidelines recommend that patients treated with highly emetogenic chemotherapy also receive a 3-drug antiemetic regimen initiated on the day of and continued for 3 days after chemotherapy administration, with the most commonly used 3-drug regimen consisting of an NK1 receptor antagonist, a 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, and dexamethasone. Developments in the area of CINV management in recent years include the use of olanzapine in combination with a 5-HT3 antagonist and dexamethasone; Food and Drug Administration (FDA) approval of the NK1 receptor antagonist rolapitant, which provides a longer duration of effect than aprepitant; FDA approval of a combination product containing palonosetron and the NK1 receptor antagonist netupitant; and revisions of U.S. practice guidelines ending palonosetron's status as the preferred 5-HT3 antagonist for prevention of CINV associated with moderately or highly emetogenic chemotherapy. Newer therapeutic options for the management of CINV are equivalent to standard-of-care regimens in terms of efficacy and toxicity. While the NK1 receptor antagonist rolapitant and a product combining palonosetron and netupitant have potential advantages over standard therapy in terms of convenience or pharmacologic properties, their relatively high costs must be considered.

Rolapitant Absolute Bioavailability and PET Imaging Studies in Healthy Adult Volunteers

Rolapitant, a selective, long-acting neurokinin-1 (NK-1) receptor antagonist, demonstrated efficacy in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving highly or moderately emetogenic chemotherapy. Two studies in healthy volunteers evaluated 1) absolute bioavailability and 2) NK-1 receptor occupancy of oral rolapitant. Absolute bioavailability, determined by the ratio of dose-normalized exposure following a 180-mg oral dose vs. an intravenous microdose, was ∼100%. Brain imaging by positron emission tomography 120 h after a single dose showed that NK-1 receptor occupancy increased with escalating doses (4.5-180 mg) but was not dose-proportional; a 180-mg dose resulted in near-saturable binding to NK-1 receptors (mean ± standard deviation: 94% ± 9%). A pharmacokinetic-pharmacodynamic model predicted that rolapitant plasma concentrations >348 ng/mL would result in >90% NK-1 receptor occupancy in the cortex up to 120 h postdose. These results support administration of a single 180-mg oral dose of rolapitant for CINV prevention.

Efficacy and safety of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis.

Olanzapine is an anti-psychotic drug that has been used for preventing and treating Chemotherapy-Induced Nausea and Vomiting (CINV). This study aimed to systematically review and meta-analyze the efficacy and safety of olanzapine for prophylaxis and treatment of CINV. We conducted a systematic literature search of MEDLINE, EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Trials-CENTRAL up to July 15, 2016. All observational and intervention studies were included, but only the intervention studies were pooled for meta-analysis. The efficacy outcome was the proportion of patients achieving complete response (CR) - no emesis and no rescue therapy, in the acute, delayed, and overall phases. The safety outcomes were the adverse events associated with olanzapine according to Common Terminology Criteria for Adverse Events (CTCAE). Sixteen studies were eligible: 15 clinical trials and 1 observational study. Nine of the interventional studies were pooled for meta-analysis. The CR of olanzapine was superior to other anti-emetic regimens, in both the delayed and overall phases (RR=1.27, 95% CI 1.07-1.49, RR=1.32, 95% CI 1.08-1.62, respectively). However, olanzapine was not better than standard CINV prophylaxis of the nausea and emesis outcome in the acute phase. Drowsiness and constipation were the most reported adverse events. No grade 3 or 4 adverse events were reported. Olanzapine is effective and safe at reducing during the delayed and overall phase of the CINV prevention. Other regimens might be added, in cases of CINV during the acute phase of CINV.

Abstract P5-11-15: Rolapitant for the prevention of chemotherapy-induced nausea and vomiting in breast cancer patients receiving multiple cycles of emetogenic chemotherapy

Abstract Background: Patients (pts) with breast cancer often receive highly emetogenic chemotherapy, such as anthracycline plus cyclophosphamide (AC). Additionally, young age and female gender are risk factors for chemotherapy-induced nausea and vomiting (CINV) in response to emetogenic chemotherapy. We assessed the ability of the long-acting neurokinin-1 receptor antagonist (RA), rolapitant, in the prevention of CINV over multiple cycles in pts with breast cancer Methods: This is a post hoc analysis of the prevention of CINV in a subset of pts with breast cancer from 3 similarly-designed, randomized, placebo-controlled phase 3 trials in which pts received a single oral dose of 180 mg rolapitant or placebo before chemotherapy. All pts received an oral 5-HT3 RA + dexamethasone (active control). The regimens were cisplatin-based (n=36), AC-based (n=681) or other (n=166; carboplatin, cyclophosphamide, etc). Pts who completed cycle 1 could continue the same antiemetic treatment in multiple cycles. Endpoints for cycle 1 of chemotherapy included complete response (CR; no emesis and no use of rescue medication) and no emesis, and no nausea (maximum visual analogue scale [VAS] <5 mm), in the overall (0–120 h), acute (≤24 h), and delayed (>24–120 h) phases. On days 6-8 of each subsequent chemotherapy cycle, pts self-reported the incidence of emesis or nausea interfering with normal daily life. Results: In cycle 1, CR in both the overall (62.9% rolapitant, 55.1% control; p=0.018) and delayed (66.7% rolapitant, 59.7% control; p=0.032) phases were higher with rolapitant vs control . Rolapitant also improved no emesis rates in the overall (74.4% rolapitant, 62.6% control; p<0.001) and delayed (77.2% rolapitant, 68.5% control; p=0.004) phases. Although less pts were available for follow up over multiple cycles, a numerically greater proportion of rolapitant-treated pts than control pts reported no emesis (cycles 2-6) and no interfering nausea (cycles 2-5) (table). The incidence of treatment-emergent adverse events (TEAEs) was similar for rolapitant (85.2%) and control (83.2%) during cycles 1-6. The most common TEAEs occurred at comparable rates in the rolapitant and control arms: fatigue (28.5% and 29.4%, respectively), alopecia (28.5% and 31.2%, respectively), and constipation (20.0% and 20.9%, respectively). Conclusions: Rolapitant added to 5-HT3 RA and dexamethasone therapy improved CINV control and was safe and well-tolerated in pts with breast cancer receiving multiple cycles of emetogenic chemotherapy, mostly AC and carboplatin, historically a high-risk population for CINV. Pt-Reported Response in Multiple Cycles, % (n/N)* No Emesis No Interfering Nausea CycleRolapitant 180 mgActive Controlp-value *Rolapitant 180 mgActive Controlp-value *288.3 (323/366)80.0 (308/385)0.00271.6 (262/366)68.3 (263/385)0.329390.5 (297/328)80.5 (293/364)<0.00173.8 (242/328)65.9 (240/364)0.025487.5 (266/304)82.4 (277/336)0.07579.3 (241/304)72.0 (242/336)0.033594.9 (111/117)88.2 (127/144)0.05987.2 (102/117)80.6 (116/144)0.152695.3 (102/107)88.9 (120/135)0.07184.1 (90/107)83.0 (112/135)0.811* Unstratified Cochran-Mantel-Haenszel test for between rolapitant and control difference in response rate. Citation Format: Schwartzberg L, Navari R, Arora S, Powers D, Jordan K, Rapoport B. Rolapitant for the prevention of chemotherapy-induced nausea and vomiting in breast cancer patients receiving multiple cycles of emetogenic chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-11-15.

Abstract P2-11-01: Non interventional study with netupitant/ palonosetron (NEPA) as CINV prophylaxis in highly or moderately emetogenic chemotherapy

Abstract Background Nausea and Vomiting due to cancer therapy is still a problem for patients and physicians and therefore an ongoing item of research in oncology. International antiemetic guidelines (ASCO, NCCN, MASCC/ESMO) have been published and new drugs are introduced into the market. The fixed oral combination of the NK1-receptor antagonist (RA) netupitant and the 5-HT3-RA palonosetron (NEPA) was recently approved in US and EU for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in cancer patients receiving cisplatin-based highly emetogenic (HEC) or moderately emetogenic chemotherapy (MEC). The MASCC guidelines 2016 recommend a triple combination of 5-HT3- and NK1-RA and dexamethasone given on day 1 for patients receiving HEC, anthracycline / cyclophosphamide (AC)-containing chemotherapy as well as for carboplatin-based MEC for the prevention of chemotherapy-induced nausea and vomiting (CINV). Objectives The primary endpoint of this non interventional study is the evaluation of quality of life in adult cancer patients receiving NEPA for CINV prevention in MEC or HEC. Secondary endpoints are efficacy and safety of NEPA. Methods This non-interventional study evaluates CINV prophylaxis with NEPA and QoL in 2500 cancer patients receiving single day or two day MEC or HEC in an ambulatory setting in German cancer hospitals and specialized cancer practices. NEPA is prescribed in accordance with the EU marketing authorization. Quality of life is recorded by FLIE questionnaires. Efficacy - measured as complete response (CR, no vomiting, no rescue medication) –as well as additional medication, safety and adverse events (AEs) are documented by an online questionnaire filled by the physician and a patient diary. 3 consecutive chemotherapy cycles are documented online using the ODM QuaSi documentation system. All specifications in the online documentation must be verifiable. Results 700 patients from 175 centers (93 gynaecologic oncology, 79 medical oncology, 3 urologic oncology) are included to date. The majority of patients were women (88.7%). 71% of all patients had breast cancer. 92.6% had an ECOG performance status of 0-1. 77.6% received (neo)adjuvant chemotherapy. Most common chemotherapy regimens were AC-based regimens (53.9%), carboplatin-based regimens (15.9%) and cisplatin-based regimens (12%). Efficacy data are available for 486 patients in cycle 1 and 350 patients over 3 cycles. During 3 consecutive chemotherapy cycles, 89% of patients had a CR on day 1 as recorded by patient diaries. In the delayed phase (days 2-5), 85% of patients had a CR. 93% recorded no vomiting during the entire 5 days at risk following chemotherapy and 69% reported no or only mild nausea. > 90% of the medical staff rated the efficacy of the CINV-prophylaxis with NEPA as good or very good over 3 cycles. Adverse events (AE), mostly constipation were rare and mild and only of grade 1 or 2. No serious AEs were observed. Summary NEPA is a safe and efficacious option for the prophylaxis of nausea and vomiting in highly and moderately emetogenic chemotherapy. Citation Format: Schilling JP, Karthaus M, Klare P, Guth D, Ortner PA. Non interventional study with netupitant/ palonosetron (NEPA) as CINV prophylaxis in highly or moderately emetogenic chemotherapy [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-11-01.

The risk factors for vomiting and nausea in patients with oxaliplatin-based chemotherapy: Subgroup analysis of SENRI trial.

779 Background: We previously reported, in the SENRI trial, usefulness of aprepitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in colorectal cancer patients receiving an oxaliplatin-based regimen which is classified as moderately emetogenic cancer chemotherapy. In this study, we assessed the risk factors for CINV in colorectal cancer patients who received Oxaliplatin-based chemotherapy. Methods: A total of 370 patients was analyzed as for the rate of vomiting, and significant nausea in overall phase. We also assessed the proportion of CINV in patients divided by gender. Results: First, we analyzed the risk factors for vomiting and nausea. Female gender and aprepitant use were associated with the incidence of vomiting and significant nausea. Significantly more women suffered from vomiting than men (84.5 % vs. 92.9 % in women and men, respectively; P= 0.0001). The rate of no nausea, complete response, complete protection, and total control was also lower in women. The rate of use of rescue therapy was significantly higher in women. We compared the rate of CINV between aprepitant and control groups and found that, in women, the rate of no nausea, no vomiting, and total control was higher in the aprepitant group than in the control group. Conclusions: Gender and no aprepitant use were risk factors of CINV in colorectal patients who received oxaliplatin-based chemotherapy.Aprepitant therapy was more effective for women than for men in the prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen. Clinical trial information: NCT01344304.

Comparison of Antiemetic Effectiveness of Palonosetron Versus Ondansetron in Patients on Cancer Chemotherapy: A Prospective Observational Study in South Indians.

Chemotherapy Induced Nausea and Vomiting (CINV) is the most distressing side effect of cancer chemotherapy. It can seriously produce an impact on patient's quality of life. Prevention of CINV is far more effective than treatment of an established CINV. If the patient receives an optimal antiemetic regimen during the initial course of chemotherapy, the likelihood of developing emesis is greatly reduced. Although, all first generation 5HT3 antagonists demonstrate reasonable efficacy in preventing acute CINV, delayed CINV still remains a problem. To compare the effectiveness and safety of palonosetron versus ondansetron as an antiemetic agent in patients receiving cancer chemotherapy. A prospective observational study was conducted in 106 patients in each treatment arm. Study duration was 12 months from January 2013 to January 2014. Consecutive patients diagnosed with cancer satisfying inclusion criteria, who were about to receive moderately or highly emetogenic chemotherapy were enrolled into the study after getting informed written consent. Each patient received either Intravenous (IV) palonosetron 0.25 mg or ondansetron 8 mg half an hour before chemotherapy as antiemetic. Patients were followed up for a period of five days following chemotherapy. Number of episodes, severity of vomiting and nausea and antiemetic rescue given if any were recorded. The data were graded using NCI-CTCAE (VERSION 3.0). Proportion of patients with nausea and vomiting during acute (0-24 hours), delayed (24-120 hours) and overall period (0-120 hours) in both the study groups were compared. Outcome was assessed in terms of symptom control and response. Data were analysed using SPSS-16.0 statistical software (IBM). Chi-square test was used to compare the difference in clinical response. Complete response during acute phase in ondansetron group was 80.2%, while for palonosetron it was 89.6%. During delayed phase, ondansetron and palonosetron produced complete response in 70.8% and 86.8% respectively. A total of 65.1% and 82.1% of subjects experienced complete response during the overall period in the ondansetron and palonosetron groups respectively. The difference in the response to antiemetic prophylaxis was statistically significant between the two groups for delayed (p-value = 0.006) and overall phase (p-value = 0.008). Palonosetron is clinically more efficacious than ondansetron in controlling CINV especially in delayed phase and overall period of emesis.

Rolapitant in the Current Management of Chemotherapy-induced Nausea and Vomiting

Chemotherapy-induced nausea and vomiting (CINV) has a severe detrimental effect on the quality of life of patients with cancer receiving chemotherapy, and remains one of the most feared adverse events associated with chemotherapy. However, physicians and oncology nurses often underestimate the incidence of CINV, as well as the impact of this toxicity on patients’ daily lives. Many challenges remain in the prevention and treatment of CINV, particularly in the delayed phase. The 5-hydroxytryptamine type 3 receptor antagonists (5-HT3 RAs) have demonstrated efficacy in CINV control during the acute phase (≤24 hours) but have limited utility in the delayed phase (>24–120 hours). The more recently introduced neurokinin-1 (NK-1) RAs have represented a relevant improvement in the prevention of CINV associated with the administration of highly and moderately emetogenic chemotherapy, particularly in the delayed phase. One of these, rolapitant, when given as one dose on the first day of the chemotherapy cycle, has been shown to protect against CINV during the complete cycle of chemotherapy in randomised controlled trials, as well as being effective in multiple cycles of chemotherapy.

Rolapitant for the prevention of delayed nausea and vomiting over initial and repeat courses of emetogenic chemotherapy

ABSTRACTIntroduction: Chemotherapy-induced nausea and vomiting (CINV) is a debilitating side effect of many cytotoxic chemotherapy regimens. Although sustained antiemetic control across repeated chemotherapy cycles is important for cancer treatment continuation, few studies have investigated the efficacy of antiemetic prophylaxis over multiple chemotherapy cycles.Areas covered: Here we discuss the use of antiemetic hydroxytryptamine type 3 (5-HT3) receptor and neurokinin (NK)-1 receptor antagonists for prevention of CINV, limiting our review to clinical trials in the context of multiple-cycle chemotherapy, with a focus on the NK-1 receptor antagonist rolapitant. 5-HT3 receptor antagonists may be effective in controlling CINV over repeated chemotherapy cycles, but evidence comes primarily from noncomparative studies. NK-1 receptor antagonists provide increased protection against CINV but differences in endpoint selection and methods of analysis preclude meaningful comparisons between agents. Rolapitant shows sustained control of emesis and nausea over multiple cycles of chemotherapy, and compared to other NK-1 receptor antagonists, has a longer half-life and reduced potential for cytochrome P450 3A4-mediated drug-drug interactions.Expert commentary: Trial design should be a key consideration in future studies of CINV therapies, including analytical methods utilized, choice of endpoints, and methods for accounting for nonresponders and patient attrition over multiple cycles of chemotherapy.

Chemotherapy-Induced Nausea and Vomiting (CINV) - First Results of a German Non-Interventional Study with NEPA - a Netupitant/Palonosetron Fixed Dose Combination

Introduction: Platinum and anthracyclin chemotherapy regimens are frequently used in hematology pts and compromised by severe acute and delayed CINV. NEPA, a fixed dose combination of the long lasting NK1-receptor antagonist (RA) netupitant and the pharmacological distinct 5HT3-RA palonosetron, has been approved by FDA and EMA for the prevention of acute and delayed CINV receiving highly emetogenic cisplatin- and AC-based as well as moderately emetogenic chemotherapy. A German non-interventional study is currently investigating NEPA's efficacy and impact on quality of life in adult cancer patients by PRO and physicians' personal assessment under real life conditions.Objectives: Primary objective is to evaluate quality of life (QoL) in adult patients receiving NEPA for CINV prevention. Secondary endpoints are efficacy and safety of NEPA.Methods: This open label, non-interventional, prospective, national, multicenter study evaluates CINV prevention and patients' QoL with NEPA in 2,500 pts receiving either highly or moderately emetogenic cytostatics on up to 2 consecutive days. NEPA is prescribed in accordance with the EU marketing authorization. QoL is evaluated by the validated FLIE questionnaire for 3 chemotherapy cycles 24 hours before, within 24 hours after and additional 4 days after chemotherapy. Efficacy is documented via patient diaries for the same time period. Safety and physicians' overall satisfaction is reported via eCRF. The interim analysis reports on the first 20% of the pre-planned number of patients.Results: Between June 2015 and July 2016 a total of 583 patients were enrolled. Median age was 56 (range of 28-88) with 521 out of 583 patients that completed documentation. A total of 291 patients (56%) received AC-based chemotherapy. Efficacy, evaluated by physicians’ personal assessment on a 4-point scale, was rated very good or good for 486 (90.7%), 409 (93.4%) and 350 (92.9%) patients in cycle 1, 2 and 3, respectively. Complete response was analyzed based on 87 completed patient diaries. Here, 88.5% reported no emesis and no rescue medication in the acute phase (0-24h post chemotherapy), while 85.1% and 79.3% reported complete response in the delayed (>24-120h post chemotherapy) and overall phase (0-120h post chemotherapy). A high percentage of patients did not suffer from any emesis (94%, 99% and 93% in acute, delayed and overall phase). The study is ongoing.Conclusions: NEPA proved to be highly effective for prevention of chemotherapy-induced emesis and nausea. Patient reported outcome was rated very good or good in more than 90% of Ctx cycles in the acute as the delayed phase of highly and moderately emetogenic Ctx including cisplatin or anthracyclin based therapy. DisclosuresKarthaus:HELSINN: Honoraria; RIEMSER: Honoraria. Schilling:RIEMSER: Honoraria.

Chemotherapy-Induced Nausea and Vomiting (CINV) in Hematologic Malignancy Patients Receiving Multi-Day Highly Emetogenic Chemotherapy (HEC)

INTRODUCTIONDespite recent advances in CINV prophylaxis, many questions remain unanswered including optimal treatment for hematologic malignancy (HM) patients receiving multi-day chemotherapy regimens. As preparation for stem cell transplant (SCT) and for high grade HM, highly emetogenic chemotherapy (HEC) containing regimens are often utilized. International guidelines recommend a three-drug combination of a 5-HT3receptor antagonist (5-HT3 RA), an NK-1 receptor antagonist (NK-1 RA) and dexamethasone (dex) before HEC. Little is known about CINV prevention in HM multi-day regimens.METHODSWe conducted a prospective observational study in U.S. research centers with expertise in HM and SCT surveying providers and adult patients receiving up to 7 consecutive days of chemotherapy including at least one HEC drug. Those receiving concurrent radiation therapy were excluded as were patients taking antiemetics or having nausea and vomiting prior to initiation of chemotherapy. Patients completed a diary and a modified Functional Living Index - Emesis (FLIE) questionnaire daily, beginning at screening, during chemotherapy, and for up to 5 days after the last day of treatment. Daily use of scheduled antiemetics and rescue medication was collected. The primary objective was to survey patterns of CINV care for multi-day chemotherapy in HM and assess efficacy of the intervention.RESULTSSeventy-six patients were enrolled at 5 centers (range 8 -25 patients per center) between May 2015 and February 2016. Of the patients, 72 underwent pre-SCT conditioning and 4 multi-day chemotherapy for HM. Forty-nine (68%) were male and 58 (81%) were Caucasian; median age was 58 (range 22-74). The most common diagnoses were NHL, 27 (36%); multiple myeloma, 19 (25%); and AML, 15 (20%). Seventy-one patients completed all surveys. All received ≥ 1 HEC drug on day 1. The most common chemotherapy regimens were BEAM, 28 (37%), high-dose melphalan, 18 (26%), melphalan, fludarabine, and campath, 8 (11%) and fludarabine and cyclophosphamide, 4 (5%). Anti-emetic therapy was highly variable, both prior to day 1 chemotherapy and throughout multi-day treatment. On day 1 the most common regimens included: a combination of 5-HT3 RA, NK-1 RA, dex in 28 (37%); 5-HT3 RA + dex in 24 (32%); 5-HT3 RA alone in 9 (12%); 5-HT3 RA and metoclopramide in 2 (3%); other 10 (13%) and none documented 3 (4%). Complete response rate (defined as no vomiting and no use of rescue medications) was observed in 15 patients (20%); complete response by day ranged from 95% on day 1 to 46% on end of study day (p=0.041). Mean±SD nausea scores by FLIE increased from 19.9±3.1 pretreatment to 22.4±3.3 overall (p=0.0031).CONCLUSIONApproaches to CINV in SCT and HM patients receiving multi-day HEC regimens are highly variable. A large majority of patients receiving multi-day chemotherapy are not achieving adequate control of nausea or vomiting. Additional clinical trials and development of evidence-based approaches to CINV prophylaxis in HM patients throughout multi-day chemotherapy are critical to improve supportive care. DisclosuresSchwartzberg:Helsinn: Consultancy, Research Funding; Eisai: Consultancy; Tesaro: Consultancy; Heron: Consultancy. Roeland:Teva: Speakers Bureau; Insys: Consultancy; Helsinn: Consultancy; Heron: Consultancy; AstraZeneca: Consultancy, Research Funding; Eisai: Speakers Bureau.

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.

Applicability of the National Comprehensive Cancer Network/Multinational Association of Supportive Care in Cancer Guidelines for Prevention and Management of Chemotherapy-Induced Nausea and Vomiting in Southeast Asia: A Consensus Statement.

A meeting of regional experts was convened in Manila, Philippines, to develop a resource-stratified chemotherapy-induced nausea and vomiting (CINV) management guideline. In patients treated with highly emetogenic chemotherapy in general clinical settings, triple therapy with a serotonin (5-hydroxytryptamine-3 [5-HT3]) antagonist (preferably palonosetron), dexamethasone, and aprepitant is recommended for acute CINV prevention. In resource-restricted settings, triple therapy is still recommended, although a 5-HT3 antagonist other than palonosetron may be used. In both general and resource-restricted settings, dual therapy with dexamethasone (days 2 to 4) and aprepitant (days 2 to 3) is recommended to prevent delayed CINV. In patients treated with moderately emetogenic chemotherapy, dual therapy with a 5-HT3 antagonist, preferably palonosetron, and dexamethasone is recommended for acute CINV prevention in general settings; any 5-HT3 antagonist can be combined with dexamethasone in resource-restricted environments. In general settings, for the prevention of delayed CINV associated with moderately emetogenic chemotherapy, corticosteroid monotherapy on days 2 and 3 is recommended. If aprepitant is used on day 1, it should be continued on days 2 and 3. Prevention of delayed CINV with corticosteroids is preferred in resource-restricted settings. The expert panel also developed CINV management guidelines for anthracycline plus cyclophosphamide combination schedules, multiday cisplatin, and chemotherapy with low or minimal emetogenic potential, and its recommendations are detailed in this review. Overall, these regional guidelines provide definitive guidance for CINV management in general and resource-restricted settings. These consensus recommendations are anticipated to contribute to collaborative efforts to improve CINV management in Southeast Asia.

Impact of adherence to antiemetic guidelines on the incidence of chemotherapy-induced nausea and vomiting and quality of life.

Background International guidelines are tools enabling physicians to incorporate the latest evidence based clinical information into practice. Objective This study aimed to evaluate the impact of antiemetic guidelines adherence on the incidence of chemotherapy-induced nausea and vomiting (CINV) and patient quality of life. Setting Marmara University Pendik Training and Research Hospital chemotherapy unit, Istanbul, Turkey. Method The study included 100 chemotherapy naive patients. Antiemetic prescribing patterns and their consistency with MASCC/ESMO 2014 guidelines were assessed. Patients recorded incidences of vomiting in a daily dairy and described their nausea using a 7-item Likert Scale. The incidence of CINV was recorded over five days. To assess the patient's quality of life, a modified Turkish version of the Functional Living Index-Emesis (FLIE) questionnaire was administered before and after receiving chemotherapy. A questionnaire on the existence and severity of side effects was developed and administered. Main outcome measures Incidence of side effects on CINV and quality of life according to the FLIE. Results The primary outcome revealed differences in complete control (no emetic episodes, rescue therapy or nausea), FLIE scores and side effects. Guidelines consistency was observed more with acute (A) than with delayed (D) prevention of CINV, with significant differences in complete control between the guideline adherent group (GAG) and the guideline nonadherent group (GNG). Significant differences in the FLIE score were noticed between GAG(D) and GNG(D), and GNG(D) had a higher incidence of diarrhoea, headache, swallowing difficulties and dark-coloured stool. Conclusion Consistency with guidelines resulted in significant reduction in the incidence of both cute and delayed CINV and other side effects, and with improvement of the patient quality of life.