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Therapeutics and Clinical Risk... 2021Our aim was to compare the antiemetic efficacy of the triple combination of aprepitant, dolasetron and dexamethasone with the combination of dolasetron and dexamethasone...
PURPOSE
Our aim was to compare the antiemetic efficacy of the triple combination of aprepitant, dolasetron and dexamethasone with the combination of dolasetron and dexamethasone for chemotherapy-induced nausea and vomiting (CINV) in hepatocellular carcinoma (HCC) patients receiving hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil and leucovorin (FOLFOX).
PATIENTS AND METHODS
This was a retrospective study. In the dolasetron plus dexamethasone group (D group), the patients received dolasetron (100 mg, i.v., on day 1) and dexamethasone (10 mg, i.v., on day 1) 30 min before starting administration of chemotherapeutic drugs. In the aprepitant plus dolasetron and dexamethasone group (AD group), the patients received dolasetron and dexamethasone as described above, and aprepitant (125 mg, p.o.) on day 1 followed by 80 mg on days 2 and 3. The primary endpoint was the complete response rate (CR, defined as no emetic episodes and no rescue medication use) during the first cycle of hepatic arterial infusion chemotherapy.
RESULTS
Between January 2018 and August 2019, 302 eligible patients were included: 197 in AD group and 105 in D group. Patients in AD group had significantly higher complete response rates than those in D group during the first cycle (85.8% vs 71.4%, P = 0.003) and all cycles (73.6% vs 49.5%, P<0.001). Patients in AD group had lower rescue therapy (1.5% vs 26.7%, P<0.001) and lower incidence of disruption related to chemotherapy-induced nausea and vomiting (0.5% vs 6.7%, P = 0.002) than patients in D group.
CONCLUSION
Aprepitant, dolasetron plus dexamethasone is more effective to prevent chemotherapy-induced nausea and vomiting in hepatocellular carcinoma patients treated with FOLFOX-HAIC therapy than dolasetron plus dexamethasone.
PubMed: 33519205
DOI: 10.2147/TCRM.S283192 -
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 -
BMC Medicine Jun 2015Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients, but these agents may be harmful. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Serotonin (5-HT3) receptor antagonists are commonly used to decrease nausea and vomiting for surgery patients, but these agents may be harmful. We conducted a systematic review on the comparative safety 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 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, 120 studies and 27,787 patients were included after screening of 7,608 citations and 1,014 full-text articles. Significantly more patients receiving granisetron plus dexamethasone experienced an arrhythmia relative to placebo (odds ratio (OR) 2.96, 95 % confidence interval (CI) 1.11-7.94), ondansetron (OR 3.23, 95 % CI 1.17-8.95), dolasetron (OR 4.37, 95 % CI 1.51-12.62), tropisetron (OR 3.27, 95 % CI 1.02-10.43), and ondansetron plus dexamethasone (OR 5.75, 95 % CI 1.71-19.34) in a NMA including 31 randomized clinical trials (RCTs) and 6,623 patients of all ages. No statistically significant differences in delirium frequency were observed across all treatment comparisons in a NMA including 18 RCTs and 3,652 patients.
CONCLUSION
Granisetron plus dexamethasone increases the risk of arrhythmia.
Topics: Antiemetics; Humans; Postoperative Nausea and Vomiting; Registries; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 26084332
DOI: 10.1186/s12916-015-0379-3 -
Structure (London, England : 1993) Oct 2020Inaccurately perceived as niche drugs, antiemetics are key elements of cancer treatment alleviating the most dreaded side effect of chemotherapy. Serotonin 5-HT3...
Inaccurately perceived as niche drugs, antiemetics are key elements of cancer treatment alleviating the most dreaded side effect of chemotherapy. Serotonin 5-HT3 receptor antagonists are the most commonly prescribed class of drugs to control chemotherapy-induced nausea and vomiting. These antagonists have been clinically successful drugs since the 1980s, yet our understanding of how they operate at the molecular level has been hampered by the difficulty of obtaining structures of drug-receptor complexes. Here, we report the cryoelectron microscopy structure of the palonosetron-bound 5-HT3 receptor. We investigate the binding of palonosetron, granisetron, dolasetron, ondansetron, and cilansetron using molecular dynamics, covering the whole set of antagonists used in clinical practice. The structural and computational results yield detailed atomic insight into the binding modes of the drugs. In light of our data, we establish a comprehensive framework underlying the inhibition mechanism by the -setron drug family.
Topics: Animals; Antiemetics; Binding Sites; Cryoelectron Microscopy; Hydrogen Bonding; Mice; Molecular Dynamics Simulation; Palonosetron; Protein Conformation; Receptors, Serotonin, 5-HT3; Serotonin; Serotonin 5-HT3 Receptor Antagonists
PubMed: 32726573
DOI: 10.1016/j.str.2020.07.004 -
The Journal of International Medical... Jun 2022To investigate the occurrence rate and risk factors of postoperative nausea and vomiting (PONV) in lung cancer patients following lobectomy and application of analgesic...
OBJECTIVE
To investigate the occurrence rate and risk factors of postoperative nausea and vomiting (PONV) in lung cancer patients following lobectomy and application of analgesic pumps.
METHODS
This retrospective study reviewed clinical data from patients that had undergone lobectomy for lung cancer under general anaesthesia. The risk factors of PONV were analysed using binary logistic regression models.
RESULTS
A total of 203 patients (97 females) were enrolled. The rate of PONV was 29.6% (60 of 203 patients) for all patients, 42.3% (41 of 97 patients) for female patients and 17.9% (19 of 106 patients) for male patients. Female patients undergoing thoracotomy (odds ratio [OR] 7.770, 95% confidence interval [CI] 1.747, 34.568) or having surgery durations ≥120 min (OR 4.493, 95% CI 1.502, 12.851) were significantly more susceptible to PONV. The risk of PONV in female patients that received postoperative dolasetron (100 mg, once a day) was significantly lower (OR 0.075, 95% CI 0.007, 0.834). For male patients, the risk of PONV was significantly lower in those with a body mass index ≥24 kg/m (OR 0.166; 95% CI 0.035, 0.782).
CONCLUSION
Female and male patients have different risk factors for PONV following lobectomy for lung cancer and application of analgesic pumps.
Topics: Analgesics; Antiemetics; Female; Humans; Incidence; Lung Neoplasms; Male; Postoperative Nausea and Vomiting; Retrospective Studies; Risk Factors
PubMed: 35735025
DOI: 10.1177/03000605221105343 -
European Journal of Hospital Pharmacy :... May 2017Patients can benefit from the coadministration of several medications because of the shorter infusion time and more rapid administration. The use of extemporaneously...
OBJECTIVES
Patients can benefit from the coadministration of several medications because of the shorter infusion time and more rapid administration. The use of extemporaneously prepared admixtures of dexamethasone sodium phosphate (DSP) and 5-HT receptor antagonists (5-HT3RAs) must be supported by sufficient documentation of their compatibility. The objective of this study was to comprehensively investigate the compatibility of DSP with 5-HT3RAs in infusion solutions.
METHODS
Admixtures of DSP with six different 5-HT3RAs (ondansetron hydrochloride, tropisetron hydrochloride, dolasetron mesylate, azasetron hydrochloride, palonosetron hydrochloride and ramosetron hydrochloride) were prepared in non-polyvinyl chloride (non-PVC) infusion bags filled with 5% glucose or 0.9% NaCl. Bags were stored at ambient temperature (25±2°C) without protection from light. Samples were taken immediately after preparation (0 hour) and at predetermined intervals (12, 24 and 48 hours after preparation). Particulate matter of admixtures was inspected visually and particles were counted with a particle counter. The pH of each sample was also determined. Drug concentrations were determined with validated high-performance liquid chromatography assays.
RESULTS
No visible haze or particulate formation, colour change or gas evolution and no notable changes in pH were observed, and particulate matter was acceptable up to 48 hours. All preparations maintained more than 90.0% of the initial concentration over the study period.
CONCLUSIONS
All the admixtures of DSP and the 5-HT3RAs studied were compatible and stable for at least 48 hours in a 5% glucose injection or a 0.9% NaCl injection stored in non-PVC infusion bags under ambient conditions.
PubMed: 31156929
DOI: 10.1136/ejhpharm-2016-000980 -
The Oncologist Apr 2016Standard prophylaxis for chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a...
BACKGROUND
Standard prophylaxis for chemotherapy-induced nausea and vomiting (CINV) with highly emetogenic and anthracycline-cyclophosphamide-based chemotherapy includes a 5-hydroxytryptamine-3 receptor antagonist, a neurokinin-1 receptor antagonist (NK1RA), and corticosteroid therapy. NEPA is a fixed combination of netupitant and palonosetron. The primary objective of this analysis was to document the safety profile, including cardiac safety, of NEPA + dexamethasone in comparison with current therapies across all phase II/III trials.
MATERIALS AND METHODS
This pooled analysis was based on data from 3,280 patients in 4 randomized, double-blind clinical trials. Patients were categorized into 1 of 3 pooled groups on the basis of actual treatment received: NEPA + dexamethasone, palonosetron + dexamethasone, and aprepitant + ondansetron/palonosetron + dexamethasone. Safety was assessed by number and frequency of adverse events (AEs) and changes from baseline electrocardiogram measures.
RESULTS
Most patients were female and younger than 65 years of age. Demographic characteristics varied among studies and pooled groups. Frequencies of treatment-emergent AEs (TEAEs) and treatment-related AEs (TRAEs) were similar across groups. TEAEs were mostly mild and consistent with expected chemotherapy and disease-related AEs (hematologic events, hair loss, general weakness). TRAEs in ≥2% of patients were headache and constipation. Frequencies of cardiac TEAEs were similar across groups, with QT prolongation (1.6%), tachycardia (1.1%), and dyspnea (0.9%) the most common. Serious cardiac TEAEs were rare.
CONCLUSION
NEPA was well-tolerated, with an AE profile as expected for the regimen. Sample size, demographic characteristics, study design, chemotherapy, and antiemetic regimen differences across the four studies may have contributed to differences in frequencies of neutropenia and alopecia. Adding an NK1RA to a CINV prophylaxis regimen can improve outcomes without additional toxicity.
IMPLICATIONS FOR PRACTICE
Supportive care for cancer should ideally be efficacious, convenient, and well-tolerated. There have been concerns about cardiac safety with current antiemetic prophylactic agents, namely dolasetron and ondansetron. This pooled safety analysis demonstrates that the new oral fixed combination therapy NEPA can be safely added to an antiemetic regimen without increased toxicity.
Topics: Adult; Aged; Antiemetics; Biomarkers, Pharmacological; Dexamethasone; Drug Combinations; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Pyridines; Quinuclidines; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 27000465
DOI: 10.1634/theoncologist.2015-0301 -
The Journal of Community and Supportive... Jul 2014No clinical standard currently exists for the optimal management of nausea induced by emetogenic chemotherapy, 7particularly delayed nausea.
BACKGROUND
No clinical standard currently exists for the optimal management of nausea induced by emetogenic chemotherapy, 7particularly delayed nausea.
OBJECTIVES
To compare the effcacy and safety of palonosetron with older 5-HT3 receptor antagonists (RAs) in preventing chemotherapy-induced nausea.
METHODS
Data were pooled from 4 similarly designed multicenter, randomized, double-blind, clinical trials that compared single intravenous doses of palonosetron 0.25 mg or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg, administered 30 minutes before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Pooled data within each chemotherapy category (MEC: n = 1,132; HEC: n = 1,781) were analyzed by a logistic regression model. Nausea endpoints were complete control rates (ie, no more than mild nausea, no vomiting, and no rescue medication), nausea-free rates, nausea severity, and requirement for rescue antiemetic/antinausea medication over 5 days following chemotherapy. Pooled safety data were summarized descriptively.
RESULTS
Numerically more palonosetron-treated patients were nausea-free on each day, and fewer had moderate-severe nausea. Similarly, usage of rescue medication was less frequent among palonosetron-treated patients. Complete control rates for palonosetron and older 5-HT3 RAs in the acute phase were 66% vs 63%, 52% vs 42% in the delayed phase (24-120 hours), and 46% vs 37% in the overall phase. The incidence of adverse events was similar for palonosetron and older 5-HT3 RAs.
LIMITATIONS
This post hoc analysis summarized data for palonosetron and several other 5-HT3 RAs but was not powered for statistical comparisons between individual agents. Because nausea is inherently subjective, the reliability of assessments of some aspects (eg, severity) may be infuenced by interindividual variability.
CONCLUSION
Palonosetron may be more effective than older 5-HT3 RAs in preventing nausea, with comparable tolerability.
DISCLOSURES AND FUNDING
Dr Schwartzberg is a consultant to and Dr Cox an employee at Esai. Mr Ballinari is a member of staff at and Dr Thorn consults for Helsinn Healthcare SA. Funding to support this study and the preparation of this manuscript was provided by Eisai Inc.
PubMed: 25830233
DOI: 10.12788/jcso.0058 -
Cancer Management and Research 2016[This corrects the article on p. 67 in vol. 4, PMID: 22427733.].
[This corrects the article on p. 67 in vol. 4, PMID: 22427733.].
PubMed: 27390532
DOI: 10.2147/CMAR.S115369 -
Journal of Pharmaceutical Analysis Dec 2016A simple and straightforward method for the determination of dolasetron mesylate (DM) in aqueous solution was developed based on the fluorescence quenching of...
A simple and straightforward method for the determination of dolasetron mesylate (DM) in aqueous solution was developed based on the fluorescence quenching of 3-Mercaptopropionic acid (MPA) capped CdS quantum dots (QDs). The structure, morphology, and optical properties of synthesized QDs were characterized by using UV-Vis absorption spectroscopy, fluorescence spectroscopy, transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements. Under the optimum conditions, the MPA-CdS QDs fluorescence probe offered good sensitivity and selectivity for detecting DM. The probe provided a highly specific selectivity and a linear detection of DM in the range of 2-40 µg/mL with detection limit (LOD) 1.512 µg/mL. The common excipients did not interfere in the proposed method. The fluorescence quenching mechanism of CdS QDs is also discussed. The developed sensor was applied to the quantification of DM in urine and human serum sample with satisfactory results.
PubMed: 29404011
DOI: 10.1016/j.jpha.2016.07.002