Efficacy of NEPA, a novel combination of netupitant (NETU) and palonosetron (PALO), for prevention of chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 9512-9512 ◽  
Author(s):  
Paul Joseph Hesketh ◽  
Giorgia Rossi ◽  
Giada Rizzi ◽  
Marco Palmas ◽  
Anna Alyasova ◽  
...  
Keyword(s):  
Complete Response ◽  
Complete Protection ◽  
Ecg Changes ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Oral Dexamethasone ◽  
Parallel Group ◽  
Dose Combination ◽  
Oral Doses ◽  
Significant Nausea

9512 Background: Further progress in preventing CINV will require the introduction of novel agents providing maximal convenience and with efficacy for nausea as well as vomiting. NEPA is a single dose combination of NETU, a novel NK1 receptor antagonist (RA) and PALO, a pharmacologically distinct 5-HT3RA. This study was designed to determine the proper dose of NETU to combine with PALO. Methods: This was a randomized, double-blind, parallel group study in chemotherapy-naïve patients (pts) undergoing cisplatin-based HEC. Four study arms compared 3 oral doses of NEPA (NETU 100, 200, 300mg + PALO 0.50 mg) with oral PALO 0.50 mg, all given on day 1. All pts received oral dexamethasone (DEX) days 1-4. An exploratory aprepitant (APREP) + ondansetron/DEX arm was included. The primary endpoint was complete response (CR: no emesis, no rescue) in the overall (0-120h) phase. Results: 694 pts were enrolled with comparable characteristics across groups: males (57%), median age 55. Common cancers: lung (27%), head and neck (21%). Median cisplatin dose: 75 mg/m2. All NEPA groups showed superior CR rates compared with PALO during the overall and delayed phases, with NEPA300also superior to PALO during the acute phase. NEPA300was also superior to PALO during all phases for no emesis, no significant nausea and complete protection with incremental benefits over lower NEPA doses. AEs were comparable across groups with no dose-response. The % of pts developing ECG changes was comparable across groups. Conclusions: Each NEPA dose resulted in superior CR rates compared with PALO. NEPA300was the best dose studied, with an advantage over lower doses for all efficacy endpoints (including nausea). NEPA doses were well tolerated with similar safety profiles to PALO and APREP. NEPA combined with DEX is superior to PALO plus DEX in prevention of CINV following HEC. [Table: see text]

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting (CINV) in patients (pts) receiving anthracycline-cyclophosphamide (AC)-based chemotherapy.

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 208-208
Author(s):  
Daniel Powers ◽  
Ian D. Schnadig ◽  
Manuel R. Modiano ◽  
Sujata Arora ◽  
Lee Steven Schwartzberg
Keyword(s):  
Active Control ◽  
Rescue Medication ◽  
Complete Response ◽  
Controlled Study ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Post Hoc ◽  
And Control ◽  
Significant Nausea ◽  
Clinical Trial Information

208 Background: Rolapitant, a novel NK-1 receptor antagonist, demonstrated efficacy in the prevention of CINV in pts receiving moderately- or highly emetogenic chemotherapy (MEC; HEC). In this post-hoc analysis, we evaluated safety and efficacy outcomes in pts receiving AC-based therapy, now considered HEC. Methods: This double-blind, active-controlled study randomized pts to oral rolapitant 180 mg plus granisetron 2 mg and dexamethasone 20 mg or granisetron/dexamethasone alone (active control). Complete response (CR = no emesis and no use of rescue medication), no emesis, no significant nausea, and time to emesis or rescue medication during overall, acute, and delayed phases and treatment-emergent adverse events (AEs) are presented. Results: 703 pts received AC-based therapy, of which 97% had breast cancer. CR was significantly higher for rolapitant vs. active control for delayed and overall phases in pts receiving AC-based therapy (Table). Time to first emesis or use of rescue medication was significantly longer with rolapitant vs. active control (between-group comparison, p = 0.032); median was not reached in either treatment arm. A significantly greater proportion of pts on rolapitant (73.0%) vs. active control (60.2%) had no emesis during the overall phase (p < 0.001). Rates of no significant nausea were similar for rolapitant (63.7%) and active control (62.4%) in the overall phase (p = 0.728). Treatment-related AEs (TRAEs) during Cycle 1 occurred in 8.7% and 8.8% of pts on rolapitant vs. active control. Most frequent TRAEs were constipation (2.9% vs. 2.7%), fatigue (2.3% vs. 2.2%), and headache (2.3% vs. 3.3%). Conclusions: Rolapitant was superior to active control in preventing CINV during delayed and overall phases after AC-based chemotherapy. The safety profiles of the rolapitant and control arms were similar. These results are consistent with those of the overall pt population in this study. Clinical trial information: NCT01500226. [Table: see text]

Efficacy of Thalidomide in Preventing Delayed Nausea and Vomiting Induced by Highly Emetogenic Chemotherapy: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Trial (CLOG1302 study)

2017 ◽  
Vol 35 (31) ◽  
pp. 3558-3565 ◽  
Author(s):  
Lingyun Zhang ◽  
Xiujuan Qu ◽  
Yuee Teng ◽  
Jing Shi ◽  
Ping Yu ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Phase Iii ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Delayed Nausea

Purpose We examined the efficacy and safety of thalidomide (THD) for the prevention of delayed nausea and vomiting in patients who received highly emetogenic chemotherapy (HEC). Patients and Methods In a randomized, double-blind, active-controlled, phase III trial, chemotherapy-naive patients with cancer who were scheduled to receive HEC that contained cisplatin or cyclophosphamide-doxorubicin/epirubincin ≥ 50 mg/m2 regimens were randomly assigned to a THD group (100 mg twice daily on days 1 to 5) or placebo group, both with palonosetron (0.25 mg on day 1) and dexamethasone (12 mg on day 1; 8 mg on days 2 to 4). Primary end point was complete response to vomiting—no emesis or use of rescue medication—in the delayed phase (25 to 120 h). Nausea and anorexia on days 1 to 5 were evaluated by the 4-point Likert scale (0, no symptoms; 3, severe). Quality of life was assessed by the European Organization for Research and Treatment of Cancer QLQ-C30 version 3 questionnaire on days −1 and 6. Results Of 656 patients, 638 were evaluable: 317 in the THD group and 321 in the control group. Compared with placebo, delayed and overall (0 to 120 h) complete response rates to vomiting were significantly higher with THD: 76.9% versus 61.7% ( P < .001) and 66.1% versus 53.3% ( P = .001), respectively. Rates of no nausea were also higher in the THD group (delayed: 47.3% v 33.3%; P < .001; overall: 41% v 29.6%; P = .003), and mean scores of anorexia were lower overall (0.44 ± 0.717 v 0.64 ± 0.844; P = .003). Adverse effects were mild to moderate. The THD group had increased sedation, dizziness, constipation, and dry mouth, but experienced better quality of life after chemotherapy. Conclusion Thalidomide combined with palonosetron and dexamethasone significantly improved HEC-induced delayed nausea and vomiting prevention in chemotherapy-naive patients.

Co-administration of ondansetron and casopitant mesylate, a novel NK-1 receptor antagonist, results in augmented anti-emetic activity in the ferret

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18608-18608 ◽  
Author(s):  
R. C. Gagnon ◽  
A. G. King
Keyword(s):  
Receptor Antagonist ◽  
Complete Response ◽  
Clinical Development ◽  
Phase Iii ◽  
Pharmacokinetic Analysis ◽  
Depression And Anxiety ◽  
Complete Protection ◽  
Highly Emetogenic Chemotherapy ◽  
Phase Iii Trials ◽  
Latency Duration

18608 Background: As monotherapies, ondansetron (a 5HT3 receptor antagonist) and casopitant mesylate ( GW679769 ) are effective anti-emetics in models of chemotherapy-induced nausea and vomiting in the ferret. To demonstrate the potential benefit of combination therapy, suboptimal doses of both ondansetron and casopitant mesylate were administered to ferrets receiving cisplatin. Methods: A 4x4 factorial design was utilized to test for therapeutically synergistic anti-emetic activity. Suboptimal doses (administered as monotherapy, which reduced vomiting and retching by >50% compared to control ferrets but did not result in complete protection) of each compound alone and in combination (0.3, 0.1, and 0.03 mg/kg) were administered 25 minutes prior to injection with cisplatin (10 mg/kg, IP). All emetic events/behaviors were recorded digitally via camera and DVR. Normal behaviors (eating, drinking, urination, defecation), emetic events (vomits, retches), and peri-emetic events (excessive mouth licking, burrowing, eye squinting, backward walking, and body scratching) were recorded temporally. All events were analyzed by finding the cumulative sum of events over time. Therapeutic synergy calculations were determined by analysis of variance. Results: Analysis of emetic events demonstrated the combination of ondansetron and casopitant mesylate resulted in significantly fewer events than either agent alone. Similar activity was demonstrated for vomits, retches, event latency, duration of emesis, water intake, food intake, and complete response. Conclusions: Co-administration of ondansetron and casopitant mesylate results in therapeutically synergistic anti-emetic and potential anti-nausea activity in this cisplatin-induced emesis model in ferrets. Pharmacokinetic analysis indicated no alteration of disposition of either agent. Therefore, we believe the synergy observed between ondansetron and casopitant mesylate is the result of their complementary mechanisms of pharmacologic action. Casopitant mesylate is currently in phase III trials for the prevention of PONV and CINV from moderately and highly emetogenic chemotherapy. It is also in clinical development for depression and anxiety. [Table: see text]

Impact on patients’ daily life activities of NEPA, the oral fixed-dose combination of netupitant, a new NK1 receptor antagonist (RA), and palonosetron (PALO) plus dexamethasone (DEX) versus PALO plus DEX for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC).

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 66-66 ◽  
Author(s):  
Matti S. Aapro ◽  
Giorgia Rossi ◽  
Giada Rizzi ◽  
Maria Elisa Borroni ◽  
Norman G. Nagl
Keyword(s):  
Complete Response ◽  
Emetogenic Chemotherapy ◽  
Fixed Dose Combination ◽  
Phase Iii ◽  
Fixed Dose ◽  
Double Blind ◽  
Efficacy Analysis ◽  
Daily Life Activities ◽  
Dose Combination ◽  
Delayed Phase

66 Background: Certain antiemesis guidelines recommend combining a 5-HT3 RA, a NK1RA and DEX for prevention of CINV associated with highly emetogenic chemotherapy (HEC) and with anthracycline + cyclophosphamide (AC)-based MEC. The objective of this analysis was to determine if using the oral fixed-dose combination NEPA prior to initiating AC-based chemotherapy resulted in no impact on daily living (NIDL) for patients. Methods: This phase III, multinational, randomized, double-blind, double-dummy, active-controlled, parallel group trial enrolled patients with solid tumors who were naïve to cytotoxics and scheduled to initiate AC-based chemotherapy. Patients received oral NEPA (netupitant 300 mg + PALO 0.5 mg) + oral DEX 12 mg on Day 1, or oral PALO 0.5 mg + oral DEX 20 mg on Day 1. The primary efficacy endpoint was Complete Response (CR: no emesis/no rescue medication) in the delayed phase (25-120 hours after chemotherapy) in cycle 1. Secondary endpoints including NIDL for patients was assessed using the Functional Living Index—Emesis (FLIE) during the first 120 hours. Results: 1,455 patients were randomized; 1,449 were included in the efficacy analysis. Significantly more patients achieved CR during the delayed phase in the NEPA arm compared with the PALO arm (76.9% vs 69.5%, respectively: p = 0.001). Significantly more patients in the NEPA arm reported NIDL via the FLIE (78.5% vs 72.1%: p = 0.005). A greater proportion of NEPA-treated patients reported no personal hardship imposed and no daily functioning affected (75.3% vs 70.5% and 77.1% vs 71.6%, respectively, as scored by the nausea domain of the FLIE; 95.2% vs 89.2% and 95.6% vs 89.2%, respectively, as scored by the vomiting domain of the FLIE). Adverse events were similar for both groups. Conclusions: NEPA significantly improved efficacy vs PALO for prevention of CINV in AC MEC and significantly more patients experienced NIDL compared to PALO. Both regimens were generally well tolerated.

Netupitant/palonosetron (NEPA) for prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in multiple cycles of chemotherapy.

2015 ◽  
Vol 33 (29_suppl) ◽  
pp. 211-211
Author(s):  
Lee Steven Schwartzberg ◽  
Richard J. Gralla ◽  
Kimia Kashef ◽  
Hope Rugo
Keyword(s):  
Oral Dose ◽  
Single Oral Dose ◽  
Complete Response ◽  
Control Group ◽  
Double Blind ◽  
Report Data ◽  
Multiple Cycles ◽  
To Receive ◽  
Delayed Phase ◽  
Significant Nausea

211 Background: Prevention of CINV in the delayed phase (24-120 h post-chemotherapy) and over multiple cycles of chemotherapy remains a challenge. NEPA, a fixed combination of the NK1 receptor antagonist (RA) netupitant (300 mg) and the 5-HT3 RA palonosetron (PALO; 0.5 mg), has demonstrated efficacy in multiple studies, in both acute and delayed phases, during the first cycle of moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) regimens. Two clinical trials evaluated NEPA over multiple cycles of chemotherapy. We report data for the delayed phase for each cycle. Methods: Both studies were Phase 3, double-blind, active-controlled studies. In study 1 (MEC), patients were randomized 1:1 to receive a single oral dose of NEPA (n = 724) or PALO 0.5 mg (n = 725) on Day 1; following cycle 1, patients could participate in a multi-cycle extension phase. In study 2 (MEC or HEC), patients were randomized 3:1 to receive a single oral dose of NEPA on Day 1 (n = 309) or oral aprepitant (APR) 125 mg plus oral PALO 0.5 mg on Day 1, then APR 80 mg/d on days 2 and 3 of each cycle (n = 103). In both studies, all patients also received dexamethasone. Efficacy endpoints included complete response (CR; no emesis, no rescue medication) and no significant nausea. Results: In both studies, CR rates were consistently numerically higher with NEPA (Study 1 range: 77%-89%; Study 2 range: 83%-93%) than with PALO (Study 1; range: 69%-83%) or APR/PALO (Study 2; range: 78%-88%) in each cycle up to cycle 6 (Table). In both studies, rates of no significant nausea in the NEPA group were similar to or higher than in the control group. NEPA was well tolerated in both studies; treatment-related adverse events included constipation and headache. Conclusions: These studies demonstrate sustained efficacy of NEPA (administered as a single dose on Day 1) across multiple cycles of MEC or HEC for prevention of CINV in the delayed phase. Clinical trial information: 2009-016775-30; 2010-023297-39. [Table: see text]

scholarly journals Ramosetron versus Palonosetron in Combination with Aprepitant and Dexamethasone for the Control of Highly-Emetogenic Chemotherapy-Induced Nausea and Vomiting

2020 ◽  
Vol 52 (3) ◽  
pp. 907-916 ◽  
Author(s):  
Jin Hyoung Kang ◽  
Jung Hye Kwon ◽  
Yun-Gyoo Lee ◽  
Keon Uk Park ◽  
Ho Jung An ◽  
...  
Keyword(s):  
Daily Life ◽  
Complete Response ◽  
Risk Difference ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Complete Protection ◽  
Highly Emetogenic Chemotherapy ◽  
Secondary Endpoints ◽  
To Receive

PurposeThe purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting. Materials and MethodsPatients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.ResultsA total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.ConclusionIn all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

Prevention of Highly Emetogenic Chemotherapy-Induced Vomiting: A Double Blind, Randomized Crossover Study to Compare Pancopride (LAS 30451) and Pancopride plus Dexamethasone

1995 ◽  
Vol 81 (6) ◽  
pp. 432-434 ◽  
Author(s):  
Enrique Aranda ◽  
Isidoro C. Barneto ◽  
Ma. Jesus Rubio ◽  
Rosario Gonzalez ◽  
Antonio Garcia ◽  
...  
Keyword(s):  
Side Effects ◽  
Crossover Study ◽  
Receptor Antagonist ◽  
Emetogenic Chemotherapy ◽  
Nausea And Vomiting ◽  
Complete Protection ◽  
Highly Emetogenic Chemotherapy ◽  
Double Blind ◽  
Order Of Administration ◽  
Randomized Crossover Study

Aims Pancopride (PNC) is a new 5HT3 receptor antagonist which has demonstrated complete protection from nausea and vomiting in 25-73% of patients treated with highly emetogenic chemotherapy. A double-blind, randomized crossover study was carried out to assess whether the addition of dexamethasone (DXM) to PNC increases the antiemetic efficacy. Methods PNC (0.2 mg/kg. i.v. 30 min before chemotherapy) plus placebo (PLC) was compared with PNC (same dose and schedule) plus DXM (20 mg. i.v. immediately before PNC). In the second cycle, patients received the alternative antiemetic treatment. Eighty patients were included in the study (PNC+DXM=39, PNC+PLC=41), 29 of whom were women and 51 men. Fifty-four percent of the patients in the PNC+DXM group and 59% of those in the PNC+PLC group received chemotherapy containing cisplatin. Seventy-seven patients completed the first cycle and 70 the second. Results Complete protection was obtained in 19/16 patients (50/46%) with PNC+PLC and in 32/22 (82/63%) with PNC+DXM (P<0.001). Latency was significantly longer in the PNC+DXM group. The efficacy of both treatments was unaffected by the order of administration. Side effects were mild in both groups. Conclusions The combination of PNC+DXM is more efficacious than PNC+PLC in protection against highly emetogenic chemotherapy-induced vomiting.

Assessing duration of breakthrough chemotherapy-induced nausea and vomiting (CINV): A pooled study analysis of NEPA versus aprepitant.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 12091-12091
Author(s):  
Rudolph M. Navari ◽  
Gary Binder ◽  
Erminio Bonizzoni ◽  
Rebecca Clark-Snow ◽  
Silvia Olivari Tilola ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Strong Predictor ◽  
Complete Response ◽  
Pooled Analysis ◽  
Nausea And Vomiting ◽  
Chi Square ◽  
Double Blind ◽  
Phase Duration ◽  
Antiemetic Prophylaxis ◽  
Significant Nausea

12091 Background: The historical standard clinical trial endpoint for preventing chemotherapy-induced nausea and vomiting (CINV) has been assessment of complete response (CR: no emesis and no rescue medication use) over five days. Recent evaluations focused on the duration of breakthrough CINV suggest that long duration of CINV results in more lost work time and impaired activity and is also a strong predictor for CINV in subsequent cycles. A recent pooled analysis of three similarly designed registration trials of NEPA, a fixed oral combination NK1 receptor antagonist (RA) (netupitant)/5-HT3RA (palonosetron), showed significantly higher CR rates during the delayed phase (≥24-120h) for NEPA compared to an aprepitant (APR) regimen. In this post-hoc analysis, we evaluated the extent and duration of breakthrough CINV in these pooled studies. Methods: Chemotherapy-naïve patients who received cisplatin-based chemotherapy and antiemetic prophylaxis of either a single dose of NEPA plus dexamethasone (DEX) or a 3-day APR/5-HT3 RA/DEX regimen from three randomized, double-blind pivotal trials were included. Patients without a CR were defined as treatment failures. Extent of CINV was evaluated using proportions of patients with treatment failure, emesis, and significant nausea (defined as >25 mm on a 100 mm visual analog scale). Over the 5-day overall phase, duration was categorized as 1-2, and ≥3 days. Pearson’s chi-square test was employed to compare risks between treatments for each duration category in each of the previously mentioned endpoints. Results: Among all 621 NEPA and 576 APR patients, a significantly greater proportion of APR patients experienced treatment failure, emesis, and significant nausea for ≥3 days. Specifically, among patients with treatment failure, 31% (41/134) who received NEPA and 43% (61/143) who received APR experienced breakthrough CINV for ≥3 days. Conclusions: Expanding on data suggesting single-day NEPA is more effective than 3-day APR in preventing delayed CINV, NEPA is also more effective in minimizing the extent and duration of CINV in patients with breakthrough emesis and nausea.[Table: see text]

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