Dataset Information

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

ABSTRACT: PURPOSE:The 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 Methods:Patients 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 sex, 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. RESULTS:A 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. CONCLUSION:In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

SUBMITTER: Kang JH

PROVIDER: S-EPMC7373869 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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

Kang Jin Hyoung JH Kwon Jung Hye JH Lee Yun-Gyoo YG Park Keon Uk KU An Ho Jung HJ Sohn Joohyuk J Seol Young Mi YM Lee Hyunwoo H Yun Hwan-Jung HJ Ahn Jin Seok JS Yang Ji Hyun JH Song Hunho H Koo Dong-Hoe DH Kim Jin Young JY Kim Gun Min GM Kim Hwa Jung HJ

Cancer research and treatment 20200318 3

<h4>Purpose</h4>The 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.<h4>Materials and methods</h4>Patients 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, ...[more]

PMID: 32192275

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Project description:BackgroundDespite 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).

Project description:BackgroundFor the prevention of chemotherapy-induced nausea and vomiting (CINV) during the delayed phase (24-120 hours) after moderately emetogenic chemotherapy (MEC), the use of 3-day dexamethasone (DEX) is often recommended. This study compared the efficacy and safety of two DEX-sparing regimens with 3-day DEX, focusing on delayed nausea.Patients and methodsThis open-label, randomized, phase III study was designed to demonstrate noninferiority of two DEX-sparing regimens: ondansetron + DEX on day 1 + metoclopramide on days 2-3 (MCP arm), and palonosetron + DEX on day 1 (PAL arm) versus ondansetron on day 1 + DEX on days 1-3 (DEX arm) in chemotherapy-naïve patients receiving MEC. Primary efficacy endpoint was total control (TC; no emetic episodes, no use of rescue medication, no nausea) in the delayed phase. Noninferiority was defined as a lower 95% CI greater than the noninferiority margin set at -20%. Secondary endpoints included no vomiting, no rescue medication, no (significant) nausea, impact of CINV on quality of life, and antiemetics-associated side effects.ResultsTreatment arms were comparable for 189 patients analyzed: predominantly male (55.7%), median age 65.0 years, colorectal cancer (85.7%), and oxaliplatin-based chemotherapy (81.5%). MCP demonstrated noninferiority to DEX for delayed TC (MCP 56.1% vs. DEX 50.0%; 95% CI, -11.3%, 23.5%). PAL also demonstrated noninferiority to DEX (PAL 55.6% vs. DEX 50.0%; 95% CI, -12.0%, 23.2%). There were no statistically significant differences for all secondary endpoints between treatment arms.ConclusionThis study showed that DEX-sparing regimens are noninferior to multiple-day DEX in terms of delayed TC rate in patients undergoing MEC. ClinicalTrials.gov identifier. NCT02135510.Implications for practiceChemotherapy-induced nausea and vomiting (CINV) in the delayed phase (24-120 hours after chemotherapy) remains one of the most troublesome adverse effects associated with cancer treatment. In particular, delayed nausea is often poorly controlled. The role of dexamethasone (DEX) in the prevention of delayed nausea after moderately emetogenic chemotherapy (MEC) is controversial. This study is the first to include nausea assessment as a part of the primary study outcome to better gauge the effectiveness of CINV control and patients' experience. Results show that a DEX-sparing strategy does not result in any significant loss of overall antiemetic control: DEX-sparing strategies incorporating palonosetron or multiple-day metoclopramide are safe and at least as effective as standard treatment with a 3-day DEX regimen with ondansetron in controlling delayed CINV-and nausea in particular-following MEC.

Project description:Background:Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize chemotherapy-induced nausea and vomiting (CINV) control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK1 receptor antagonist, netupitant (300?mg), and the pharmacologically distinct 5-HT3RA, palonosetron (PALO 0.50?mg), has shown superior CINV prevention compared with PALO in cisplatin and anthracycline/cyclophosphamide-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen. Patients and methods:This randomized, double-blind phase III study conducted in Asia was designed with the primary objective to demonstrate non-inferiority of a single oral dose of NEPA compared 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, no rescue medication, and no significant nausea (NSN). 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 [NEPA 73.8% versus APR/GRAN 72.4%, 95% CI (-4.5%, 7.5%)]. No emesis [NEPA 75.0% versus APR/GRAN 74.0%, 95% CI (-4.8%, 6.9%)] and NSN rates [NEPA 75.7% versus APR/GRAN 70.4%, 95% CI (-0.6%, 11.4%)] were similar between groups, but significantly more NEPA patients did not take rescue medication [NEPA 96.6% versus APR/GRAN 93.5%, 95% CI (0.2%, 6.1%)]. NEPA was well tolerated with a similar safety profile to APR/GRAN. Conclusions:In this first study comparing NK1RA regimens and DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC.

Dataset Information

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

Publications

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

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