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The Cochrane Database of Systematic... Feb 2016Nausea and vomiting remain a problem for children undergoing treatment for malignancies despite new antiemetic therapies. Optimising antiemetic regimens could improve... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Nausea and vomiting remain a problem for children undergoing treatment for malignancies despite new antiemetic therapies. Optimising antiemetic regimens could improve quality of life by reducing nausea, vomiting, and associated clinical problems. This is an update of the original systematic review.
OBJECTIVES
To assess the effectiveness and adverse events of pharmacological interventions in controlling anticipatory, acute, and delayed nausea and vomiting in children and young people (aged less than 18 years) about to receive or receiving chemotherapy.
SEARCH METHODS
Searches included the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, PsycINFO, conference proceedings of the American Society of Clinical Oncology, International Society of Paediatric Oncology, Multinational Association of Supportive Care in Cancer, and ISI Science and Technology Proceedings Index from incept to December 16, 2014, and trial registries from their earliest records to December 2014. We examined references of systematic reviews and contacted trialists for information on further studies. We also screened the reference lists of included studies.
SELECTION CRITERIA
Two review authors independently screened abstracts in order to identify randomised controlled trials (RCTs) that compared a pharmacological antiemetic, cannabinoid, or benzodiazepine with placebo or any alternative active intervention in children and young people (less than 18 years) with a diagnosis of cancer who were to receive chemotherapy.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted outcome and quality data from each RCT. When appropriate, we undertook meta-analysis.
MAIN RESULTS
We included 34 studies that examined a range of different antiemetics, used different doses and comparators, and reported a variety of outcomes. The quality and quantity of included studies limited the exploration of heterogeneity to narrative approaches only.The majority of quantitative data related to the complete control of acute vomiting (27 studies). Adverse events were reported in 29 studies and nausea outcomes in 16 studies.Two studies assessed the addition of dexamethasone to 5-HT3 antagonists for complete control of vomiting (pooled risk ratio (RR) 2.03; 95% confidence interval (CI) 1.35 to 3.04). Three studies compared granisetron 20 mcg/kg with 40 mcg/kg for complete control of vomiting (pooled RR 0.93; 95% CI 0.80 to 1.07). Three studies compared granisetron with ondansetron for complete control of acute nausea (pooled RR 1.05; 95% CI 0.94 to 1.17; 2 studies), acute vomiting (pooled RR 2.26; 95% CI 2.04 to 2.51; 3 studies), delayed nausea (pooled RR 1.13; 95% CI 0.93 to 1.38; 2 studies), and delayed vomiting (pooled RR 1.13; 95% CI 0.98 to 1.29; 2 studies). No other pooled analyses were possible.Narrative synthesis suggests that 5-HT3 antagonists are more effective than older antiemetic agents, even when these agents are combined with a steroid. Cannabinoids are probably effective but produce frequent side effects.
AUTHORS' CONCLUSIONS
Our overall knowledge of the most effective antiemetics to prevent chemotherapy-induced nausea and vomiting in childhood is incomplete. Future research should be undertaken in consultation with children, young people, and families that have experienced chemotherapy and should make use of validated, age-appropriate measures. This review suggests that 5-HT3 antagonists are effective in patients who are to receive emetogenic chemotherapy, with granisetron or palonosetron possibly better than ondansetron. Adding dexamethasone improves control of vomiting, although the risk-benefit profile of adjunctive steroid remains uncertain.
Topics: Adolescent; Antiemetics; Antineoplastic Agents; Child; Dexamethasone; Drug Therapy, Combination; Humans; Nausea; Neoplasms; Randomized Controlled Trials as Topic; Serotonin Antagonists; Vomiting
PubMed: 26836199
DOI: 10.1002/14651858.CD007786.pub3 -
BMC Medicine Jun 2015Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients. We conducted a systematic review on the comparative... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients. We conducted a systematic review on the comparative efficacy of 5-HT3 receptor antagonists.
METHODS
Searches were done in MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify studies comparing 5-HT3 receptor antagonists with each other, placebo, and/or combined with other antiemetic agents for patients undergoing surgical procedures. Screening search results, data abstraction, and risk of bias assessment were conducted by two reviewers independently. Random-effects pairwise meta-analysis and network meta-analysis (NMA) were conducted. PROSPERO registry number: CRD42013003564.
RESULTS
Overall, 450 studies and 80,410 patients were included after the screening of 7,608 citations and 1,014 full-text articles. Significantly fewer patients experienced nausea with any drug relative to placebo, except for ondansetron plus metoclopramide in a NMA including 195 RCTs and 24,230 patients. Significantly fewer patients experienced vomiting with any drug relative to placebo except for palonosetron plus dexamethasone in NMA including 238 RCTs and 12,781 patients. All agents resulted in significantly fewer patients with postoperative nausea and vomiting versus placebo in a NMA including 125 RCTs and 16,667 patients.
CONCLUSIONS
Granisetron plus dexamethasone was often the most effective antiemetic, with the number needed to treat ranging from two to nine.
Topics: Antiemetics; Humans; Postoperative Nausea and Vomiting; Registries; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 26084277
DOI: 10.1186/s12916-015-0371-y -
BMC Pharmacology & Toxicology Jan 2015Patients may experience nausea and vomiting when undergoing chemotherapy or surgery requiring anesthesia. Serotonin 5-hydroxytryptamine 3 (5-HT3) receptor antagonists... (Review)
Review
BACKGROUND
Patients may experience nausea and vomiting when undergoing chemotherapy or surgery requiring anesthesia. Serotonin 5-hydroxytryptamine 3 (5-HT3) receptor antagonists are effective antiemetics, yet may cause adverse cardiac events, such as arrhythmia. We aimed to identify interventions that mitigate the cardiac risk of 5-HT3 receptor antagonists.
METHODS
Electronic databases, trial registries, and references were searched. Studies on patients undergoing chemotherapy or surgery examining interventions to monitor cardiac risk of 5-HT3 receptor antagonists were included. Search results were screened and data from relevant studies were abstracted in duplicate. Risk of bias of included studies was assessed using the Cochrane Effective Practice and Organisation of Care (EPOC) group's risk-of-bias tool. Due to a dearth of included studies, meta-analysis was not conducted.
RESULTS
Two randomized clinical trials (RCT) and 1 non-randomized clinical trial (NRCT) were included after screening 7,637 titles and abstracts and 1,554 full-text articles. Intravenous administration of different dolasetron doses was examined in the NRCT, while dolasetron versus ondansetron and palonosetron versus ondansetron were examined in the RCT. Electrocardiogram (ECG) was the only intervention examined to mitigate cardiac harm. No differences in ECG evaluations were observed between dolasetron or palonosetron versus ondansetron after 15 minutes, 24 hours, and 1 week post-administration in the 2 RCTs. Four deaths were observed in one RCT, which were deemed unrelated to palonosetron or ondansetron administration. Minor increases in PR and QT intervals were observed in the NRCT for dolasetron dosages greater than 1.2 mg/kg 1-2 hours post-administration, but were deemed not clinically relevant.
CONCLUSIONS
ECG monitoring of chemotherapy patients administered with 5-HT3 receptor antagonists did not reveal clinically significant differences in arrhythmia between the medications at the examined time periods. The usefulness of ECG to monitor chemotherapy patients administered with 5-HT3 receptor antagonists remains unclear, as all patients received ECG monitoring.
TRIAL REGISTRATION
PROSPERO registry number: CRD42013003565.
Topics: Antiemetics; Antineoplastic Agents; Arrhythmias, Cardiac; Drug Therapy, Combination; Electrocardiography; Humans; Indoles; Isoquinolines; Ondansetron; Palonosetron; Quinolizines; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists
PubMed: 25623303
DOI: 10.1186/2050-6511-16-1 -
The Oncologist Jun 2019It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer...
BACKGROUND
It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis.
METHODS
Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided.
RESULTS
We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56-1.97, and OR, 2.25; 95% CrI, 1.66-3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR.
CONCLUSION
Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients.
IMPLICATIONS FOR PRACTICE
Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Drug Costs; Humans; Nausea; Neoplasms; Network Meta-Analysis; Olanzapine; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Vomiting
PubMed: 30333194
DOI: 10.1634/theoncologist.2018-0140 -
The Oncologist Dec 2019A dexamethasone-sparing regimen consisting of palonosetron plus 1-day dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) has been... (Meta-Analysis)
Meta-Analysis
One-Day Versus Three-Day Dexamethasone in Combination with Palonosetron for the Prevention of Chemotherapy-Induced Nausea and Vomiting: A Systematic Review and Individual Patient Data-Based Meta-Analysis.
BACKGROUND
A dexamethasone-sparing regimen consisting of palonosetron plus 1-day dexamethasone for the prevention of chemotherapy-induced nausea and vomiting (CINV) has been studied previously. Here, we evaluate the noninferiority of the dexamethasone-sparing regimen in overall antiemetic control using a meta-analysis based on individual patient data (IPD).
MATERIALS AND METHODS
We conducted a systematic review for randomized trials reporting CINV outcomes for the comparison of palonosetron plus 1-day dexamethasone (d1 arm) versus the same regimen followed by dexamethasone on days 2-3 after chemotherapy (d3 arm) in chemotherapy-naïve adult patients undergoing either moderately emetogenic chemotherapy (MEC) or anthracycline plus cyclophosphamide (AC)-containing chemotherapy. PubMed and MEDLINE were searched electronically. A manual search was also conducted. The primary endpoint was complete response (CR; no emesis and no rescue medication) in the overall 5-day study period. The noninferiority margin was set at -8.0% (d1 arm-d3 arm).
RESULTS
Five studies ( = 1,194) were eligible for analysis and all IPD was collected. In the overall study period, the d1 arm showed noninferiority to the d3 arm for CR as well as complete control (pooled risk difference in CR rate - 1.5%, 95% confidence interval [CI] -7.1 to 4.0%, I = 0%; in complete control rate - 2.4%, 95% CI -7.7 to 2.9%, I = 0%). There was no significant interaction between dexamethasone regimen and risk factors (type of chemotherapy, sex, age, and alcohol consumption).
CONCLUSION
This IPD meta-analysis indicates that the dexamethasone-sparing regimen is not associated with a significant loss in overall antiemetic control in patients undergoing MEC or AC-containing chemotherapy, irrespective of known risk factors for CINV.
IMPLICATIONS FOR PRACTICE
Although dexamethasone in combination with other antiemetic agents has been used to prevent chemotherapy-induced nausea and vomiting (CINV), it is of clinical importance to minimize total dose of dexamethasone in patients undergoing multiple cycles of emetogenic chemotherapy. This individual-patient-data meta-analysis from five randomized controlled trials (1,194 patients) demonstrated a noninferiority of the dexamethasone-sparing regimen for complete response and complete control of CINV. The outcomes were comparable across patients with different characteristics. These findings thus help physicians minimize use of the steroid and further reduce the burden of dexamethasone-related side effects in patients undergoing multiple consecutive courses of emetogenic chemotherapy.
Topics: Dexamethasone; Drug Dosage Calculations; Female; Humans; Male; Middle Aged; Nausea; Palonosetron; Vomiting
PubMed: 31217343
DOI: 10.1634/theoncologist.2019-0133 -
Frontiers in Public Health 2021The aim of this systematic review is to assess the published cost-effectiveness analyses of aprepitant for patients with chemotherapy-induced nausea and vomiting...
The aim of this systematic review is to assess the published cost-effectiveness analyses of aprepitant for patients with chemotherapy-induced nausea and vomiting (CINV). A systematic literature search was performed on PubMed, EMbase, the Cochrane Library, CNKI, WANFANG DATA, and CBM database. The date of publication is up to January 2019. Two reviewers independently reviewed titles, abstracts, and articles sequentially to select studies for data abstraction based on the inclusion and exclusion criteria. Disagreements were resolved and reviewers reached a consensus. The quality of the included studies was assessed according to the 24-item checklist of the consolidated health economic evaluation reporting standards (CHEERS). The costs reported by the included studies were converted to US dollars purchasing power parities (PPP) in the year 2019 using the CCEMG-EPPI-Certer Cost Converter. Thirteen articles were included based on the inclusion criteria for cost-effectiveness analysis and cost-utility analysis. Twelve studies were rated as good quality and one as a moderate quality based on the CHEERS checklist. Eight studies compared aprepitant plus 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and dexamethasone with the standard regimen (5-HT3RA and dexamethasone). It was concluded that aprepitant plus standard regimen was a cost-effective strategy for preventing CINV. Only one study that compared aprepitant plus 5-HT3RA with 5-HT3RA, concluded that the addition of aprepitant reduced the incidence of severe nausea, and it might also provide an economic benefit in the overall management. Four studies that compared aprepitant with other antiemetic drugs concluded that aprepitant is a cost-effective strategy for preventing CINV compared with metoclopramide. However, netupitan + palonosetron and olanzapine are cost-effective compared with aprepitant. This study is the first systematic evaluation of adding aprepitant to standard regimens for patients with CINV. Most economic evaluations of antiemetic medications are reported to be of good quality. Adding aprepitant to standard regimens is found to be a cost-effective strategy for preventing CINV.
Topics: Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Humans; Nausea; Vomiting
PubMed: 34513778
DOI: 10.3389/fpubh.2021.660514 -
Supportive Care in Cancer : Official... Aug 2015Delayed chemotherapy-induced nausea and vomiting (CINV) remains an important adverse effect of moderately emetogenic chemotherapy not containing anthracyclines and... (Review)
Review
Prophylactic treatment for delayed chemotherapy-induced nausea and vomiting after non-AC based moderately emetogenic chemotherapy: a systematic review of randomized controlled trials.
PURPOSE
Delayed chemotherapy-induced nausea and vomiting (CINV) remains an important adverse effect of moderately emetogenic chemotherapy not containing anthracyclines and cyclophosphamide (non-AC MEC). In this review, we summarize current literature to update recommendations for delayed CINV prophylaxis after non-AC MEC.
METHODS
We conducted a systematic search in PubMed and conference proceedings from ASCO, ESMO, and MASCC. Included randomized controlled trials (RCTs) aimed to prospectively evaluate the efficacy of two or more antiemetic strategies in the prevention of delayed CINV after the administration of non-AC MEC. At least one of the following endpoints was used: complete response, complete control, no nausea, no vomiting, and/or no use of rescue medication.
RESULTS
Our search provided 247 publications. Nine met the predefined criteria. Included RCTs reported outcomes on palonosetron, aprepitant, casopitant, netupitant/palonosetron (NEPA), olanzapine, and megestrol acetate.
CONCLUSIONS
Superiority of palonosetron over first-generation 5-HT3 receptor antagonists for the prevention of acute and delayed CINV after non-AC MEC has not been proven. The addition of an NK1 receptor antagonist to first-generation 5-HT3 receptor antagonists does not significantly improve the incidence of delayed CINV after non-AC MEC. The efficacy of a single-day regimen of dexamethasone with palonosetron is non-inferior to multiday dexamethasone. NEPA, olanzapine, and megestrol acetate show highly effective complete response (CR) rates.
Topics: Antiemetics; Antineoplastic Agents; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Humans; Nausea; Vomiting
PubMed: 26041480
DOI: 10.1007/s00520-015-2778-6