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Expert Review of Clinical Pharmacology Sep 2016Chemotherapy-induced nausea and vomiting are adverse effects responsible for worsening quality of life in cancer patients. To assess the efficacy, safety and... (Comparative Study)
Comparative Study Meta-Analysis Review
Efficacy, safety and effectiveness of ondansetron compared to other serotonin-3 receptor antagonists (5-HT3RAs) used to control chemotherapy-induced nausea and vomiting: systematic review and meta-analysis.
INTRODUCTION
Chemotherapy-induced nausea and vomiting are adverse effects responsible for worsening quality of life in cancer patients. To assess the efficacy, safety and effectiveness of serotonin receptor antagonist in cancer patients undergoing chemotherapy, comparing ondansetron with granisetron, dolasetron, tropisetron and palonosetron.
AREAS COVERED
Systematic review and meta-analysis. The data were collected using CINAHL; CENTRAL; MEDLINE/PubMed; and LILACS databases; grey literature; and manual search. The methodological quality was assessed using the modified Jadad scale; Cochrane Collaboration's tool for assessing risk of bias in randomized clinical trials and the Newcastle-Ottawa Scale for observational studies. The search was completed in November, 2015. 26 studies were included in the meta-analysis. Ondansetron exhibited similar efficacy than granisetron and tropisetron, as well as greater efficacy than dolasetron for acute vomiting. Palonosetron exhibited greater efficacy than ondansetron for delayed nausea and acute and delayed vomiting. The comparison of granisetron with ondansetron in the cohort studies showed no difference. Expert commentary: In this review, palonosetron had increased efficiency compared with ondansetron, except in the subgroup analysis and acute nausea. Few cohort studies have been published addressing this topic.
Topics: Antiemetics; Antineoplastic Agents; Humans; Nausea; Neoplasms; Ondansetron; Quality of Life; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Agonists; Vomiting
PubMed: 27180992
DOI: 10.1080/17512433.2016.1190271 -
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 -
Canadian Journal of Anaesthesia =... Dec 2015Palonosetron, a second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA), has unique characteristics relative to first-generation 5-HT3RAs such as... (Comparative Study)
Comparative Study Meta-Analysis Review
PURPOSE
Palonosetron, a second-generation 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA), has unique characteristics relative to first-generation 5-HT3RAs such as ondansetron. Nevertheless, it remains unclear if palonosetron is better than ondansetron for the prevention of nausea and vomiting during the first 24 hr after surgery and is thus the focus of this systematic review.
METHODS
We conducted a systematic search of the MEDLINE®, EMBASE™, Cochrane Central Register of Controlled Trials and Web of Science® databases to identify randomized controlled trials (RCTs) that addressed a comparison of the prophylactic antiemetic efficacy between palonosetron and ondansetron within 24 hr after surgery. The primary outcomes were the proportion of participants who experienced postoperative nausea (PON), postoperative vomiting (POV), or both, in the early (0-6 hr) or late (6-24 hr) period. The pooled relative risks (RRs) were calculated along with their corresponding 95% confidence intervals (CIs).
RESULTS
We identified nine RCTs that comprised 741 participants. Palonosetron was superior to ondansetron in the reduction of early PON [RR, 0.51; 95% CI, 0.37 to 0.71], late PON (RR, 0.53; 95% CI, 0.36 to 0.77), and late POV (RR, 0.41; 95% CI, 0.28 to 0.62), but not early POV (RR, 0.77; 95% CI, 0.45 to 1.34).
CONCLUSION
Palonosetron provides more effective prophylaxis of early PON, late PON, and late POV compared with ondansetron. Future studies are required to investigate the role of palonosetron during 24-72 hr following surgery.
Topics: Antiemetics; Humans; Isoquinolines; Ondansetron; Palonosetron; Postoperative Nausea and Vomiting; Quinuclidines; Randomized Controlled Trials as Topic; Time Factors
PubMed: 26296300
DOI: 10.1007/s12630-015-0457-1 -
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 -
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 -
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