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BMC Medicine Dec 2016Although serotonin (5-HT) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Although serotonin (5-HT) receptor antagonists are effective in reducing nausea and vomiting, they may be associated with increased cardiac risk. Our objective was to examine the comparative safety and effectiveness of 5-HT receptor antagonists (e.g., dolasetron, granisetron, ondansetron, palonosetron, tropisetron) alone or combined with steroids for patients undergoing chemotherapy.
METHODS
We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception until December 2015 for studies comparing 5-HT receptor antagonists with each other or placebo in chemotherapy patients. The search results were screened, data were abstracted, and risk of bias was appraised by pairs of reviewers, independently. Random-effects meta-analyses and network meta-analyses (NMAs) were conducted.
RESULTS
After screening 9226 citations and 970 full-text articles, we included 299 studies (n = 58,412 patients). None of the included studies reported harms for active treatment versus placebo. For NMAs on the risk of arrhythmia (primary outcome; three randomized controlled trials [RCTs], 627 adults) and mortality (secondary outcome; eight RCTs, 4823 adults), no statistically significant differences were observed between agents. A NMA on the risk of QTc prolongation showed a significantly greater risk for dolasetron + dexamethasone versus ondansetron + dexamethasone (four RCTs, 3358 children and adults, odds ratio 2.94, 95% confidence interval 2.13-4.17). For NMAs on the number of patients without nausea (44 RCTs, 11,664 adults, 12 treatments), number of patients without vomiting (63 RCTs, 15,460 adults, 12 treatments), and number of patients without chemotherapy-induced nausea or vomiting (27 RCTs, 10,924 adults, nine treatments), all agents were significantly superior to placebo. For a NMA on severe vomiting (10 RCTs, 917 adults), all treatments decreased the risk, but only ondansetron and ramosetron were significantly superior to placebo. According to a rank-heat plot with the surface under the cumulative ranking curve results, palonosetron + steroid was ranked the safest and most effective agent overall.
CONCLUSIONS
Most 5-HT receptor antagonists were relatively safe when compared with each other, yet none of the studies compared active treatment with placebo for harms. However, dolasetron + dexamethasone may prolong the QTc compared to ondansetron + dexamethasone. All agents were effective for reducing risk of nausea, vomiting, and chemotherapy-induced nausea or vomiting.
TRIAL REGISTRATION
This study was registered at PROSPERO: ( CRD42013003564 ).
Topics: Adult; Antiemetics; Antineoplastic Agents; Drug Therapy, Combination; Glucocorticoids; Humans; Nausea; Network Meta-Analysis; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 28007031
DOI: 10.1186/s12916-016-0761-9 -
PloS One 2016Previous randomized controlled trials have reported conflicting findings on the superiority of palonosetron over ramosetron for preventing postoperative nausea and... (Comparative Study)
Comparative Study Meta-Analysis Review
Previous randomized controlled trials have reported conflicting findings on the superiority of palonosetron over ramosetron for preventing postoperative nausea and vomiting (PONV). Therefore, the present systematic review was registered in PROSPERO (CRD42016038120) and performed to compare the efficacy of perioperative administration of palonosetron to that of ramosetron for preventing PONV. We searched MEDLINE, EMBASE, and CENTRAL to identify all randomized controlled trials that compared the effectiveness of perioperative administration of palonosetron to that of ramosetron. The primary endpoints were defined as the incidence of postoperative nausea (PON), postoperative vomiting (POV), and PONV. A total of 695 patients were included in the final analysis. Subgroup analysis was performed through administration times which were divided into two phases: the early phase of surgery and the end of surgery. Combined analysis did not show differences between palonosetron and ramosetron in the overall incidence of PON, POV or PONV. Palonosetron was more effective than ramosetron, when the administration time for the 5-HT3 receptor antagonist was during the early phase of the operation. Otherwise, ramosetron was more effective than palonosetron, when the administration time was at the end of surgery. However, the quality of evidence for each outcome was low or very low and number of included studies was small, limiting our confidence in findings.
Topics: Benzimidazoles; Female; Humans; Isoquinolines; Male; Palonosetron; Postoperative Nausea and Vomiting; Quinuclidines; Randomized Controlled Trials as Topic
PubMed: 27992509
DOI: 10.1371/journal.pone.0168509 -
International Journal of Surgery... Dec 2016A systematic review and meta-analysis of published randomized controlled trials was performed to update the present evidence about the safety and efficacy of... (Meta-Analysis)
Meta-Analysis Review
Dexamethasone combined with other antiemetics versus single antiemetics for prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy: An updated systematic review and meta-analysis.
OBJECTIVE
A systematic review and meta-analysis of published randomized controlled trials was performed to update the present evidence about the safety and efficacy of dexamethasone combined with other antiemetics versus single antiemetics for the prevention of postoperative nausea and vomiting after laparoscopic cholecystectomy.
METHODS
A computer literature search of PubMed, Scopus, Web of Science and Embase was conducted to identify the relevant randomized controlled trials. In addition, a manual search of reference lists of the retrieved articles was conducted. Relevant outcomes were pooled as odds ratio (OR) by RevMan version 5.3 for windows.
RESULTS
Pooled data from 14 RCTs (1542 patients) favored dexamethasone combined with other antiemetics over single antiemetics as a prophylaxis against postoperative nausea and vomiting after laparoscopic cholecystectomy in the early postoperative period (OR = 0.39, 95% CI [0.27 to 0.54], p < 0.00001), late postoperative period (OR = 0.36, 95% CI [0.23 to 0.56], p < 0.00001), and overall postoperative period (OR = 0.34, 95% CI [0.23 to 0.51], p < 0.00001). Subsequently, rescue antiemetic usage was significantly lower in the combination group (OR = 0.25, 95% CI [0.16 to 0.41], p < 0.00001). Subgroup analysis showed that all combinations of dexamethasone and other antiemetics were superior to corresponding singel antiemetics except for the combination of dexamethasone and ramosetron which was not superior to ramosetron alone in all postoperative periods and the combination of dexamethasone and granisetron which was not superior to granisetron alone in the early postoperative period (OR = 0.26, 95% CI [0.07 to 1.01], p = 0.05). For all adverse events, there was no significant difference between the two groups.
CONCLUSION
Dexamethasone combined with other antiemetics provided better prophylaxis than single antiemetics against postoperative nausea and vomiting after laparoscopic cholecystectomy. The underlying mechanism of dexamethasone action and its optimal dose should be further investigated.
Topics: Antiemetics; Benzimidazoles; Cholecystectomy, Laparoscopic; Dexamethasone; Drug Therapy, Combination; Granisetron; Humans; Isoquinolines; Metoclopramide; Ondansetron; Palonosetron; Postoperative Nausea and Vomiting; Quinuclidines; Randomized Controlled Trials as Topic
PubMed: 27793640
DOI: 10.1016/j.ijsu.2016.10.034 -
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 -
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