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Pharmaceuticals (Basel, Switzerland) May 2024The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative... (Review)
Review
The management of chemotherapy-induced nausea and vomiting (CINV) in children remains challenging due to differences in the chemotherapy regimens, their relative emetogenicity compared to that in adults and differences in drug metabolism and the available formulations. The common four classes of anti-emetics used for the treatment and prophylaxis of CINV in children include dexamethasone, neurokinin-1 receptor antagonists, 5-hydroxytryptamine-3 receptor antagonists (5HT3RAs), and olanzapine. The appropriate dose of dexamethasone for CINV prophylaxis in children is unknown, with a significant variability in dosage ranging between 6 and 32 mg/m/day. The dose of dexamethasone is decreased by 30% when this drug is combined with (fos)aprepitant in children, in contrast to a decrease of 50% required in adults. The use of aprepitant in younger children (<12 years) is often hampered by the non-availability of oral suspension formulations in many countries; alternatively, 80 mg capsules are administered for 1-3 days in certain institutes to children weighing between 15 and 40 kg. Among the different 5HT3RAs, palonosetron is comparatively metabolized faster in children than in adults, requiring a higher dosage for similar efficacy to that achieved in adults. Olanzapine is a newer agent, used in doses between 0.1 and 0.14 mg/kg/day in children, with good anti-emetic efficacy, but has sedation and hyperglycemia as concerning adverse effects. Drug interactions between anti-emetics and between anti-emetics and chemotherapy/supportive agents (azole antifungals, cyclosporine, arsenic trioxide), especially QTc prolongation, should be considered during prescription.
PubMed: 38794186
DOI: 10.3390/ph17050616 -
Leukemia Research Jan 2024Limited data are available regarding efficacious antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing allogeneic...
Evaluation of palonosetron, fosaprepitant, and olanzapine as antiemetic prophylaxis for fludarabine and melphalan-based conditioning regimens prior to allogeneic hematopoietic stem cell transplants.
BACKGROUND
Limited data are available regarding efficacious antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). In patients aged 60 years or older, allogeneic HSCT is associated with improved survival, but tolerability of the transplant is a significant barrier. Fludarabine and melphalan (Flu-Mel) is a frequently utilized multi-day reduced intensity conditioning regimen for allogeneic HSCT. However, the optimal CINV prevention regimen is unknown.
OBJECTIVE
The purpose of this study was to evaluate the efficacy of a novel CINV prophylaxis regimen prior to allogeneic HSCT with Flu-Mel compared to a historical control group.
STUDY DESIGN
This was a retrospective, single-center, cohort review of 123 patients who received a Flu-Mel preparative regimen prior to allogeneic HSCT from January 1, 2019, to September 30, 2022. Fifty-nine patients received high dose ondansetron (HDO) for CINV prevention, while sixty-four patients received a combination of palonosetron, fosaprepitant, and olanzapine (PFO). The primary outcome was average number of rescue antiemetic doses administered per day. A key secondary outcome was time to first rescue antiemetic.
RESULTS
The median number of antiemetic doses used per day was significantly lower in patients who received PFO compared to HDO (1.94 doses [0.31-3.60] vs 3.31 doses [1.61-4.92]; p = 0.002). In addition, use of PFO significantly prolonged the median time to first rescue antiemetic compared to HDO (41.3 h [24.3-122.7] vs 26.2 h [14.7-48.1]; p = 0.016).
CONCLUSION
The combination of palonosetron, fosaprepitant, and olanzapine is an effective antiemetic regimen for patients receiving a Flu-Mel-based preparative regimen.
Topics: Humans; Antiemetics; Palonosetron; Olanzapine; Melphalan; Retrospective Studies; Vomiting; Nausea; Ondansetron; Hematopoietic Stem Cell Transplantation; Morpholines; Vidarabine
PubMed: 38043326
DOI: 10.1016/j.leukres.2023.107431 -
Investigational New Drugs Feb 2024Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after...
Dexamethasone is one of the key antiemetic agents and is widely used even now. However, dexamethasone has been associated with several adverse reactions even after short-term administration. Therefore, developing a steroid-free antiemetic regimen is an important issue to consider. Thus, the purpose of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine in a multi-institutional phase II study. Chemotherapy-naive patients scheduled to receive cisplatin were enrolled and evaluated for the occurrence of chemotherapy-induced nausea and vomiting during 120 h after chemotherapy. The primary endpoint of the study was total control (TC) in the overall phase. The key secondary endpoint was complete response (CR), which was assessed in the acute, delayed, and overall phase, respectively. Adverse events were evaluated according to the Common Terminology Criteria for Adverse Events. Eighty-five patients were enrolled from 8 centers in Japan, of which 83 were evaluable for analyses. The percentage of patients who achieved TC during the overall phase was 31.3%. CR was achieved in 61.4%, 84.3%, and 65.1% of patients during the overall, acute, and delayed phases, respectively. The most frequently reported adverse event was anorexia. The primary endpoint was below the threshold and we could not find benefit in the dexamethasone-free regimen, but CR during the overall phase was similar to that of the conventional three-drug regimen. This antiemetic regimen without dexamethasone might be an option for patients for whom corticosteroids should not be an active application.
Topics: Humans; Antiemetics; Aprepitant; Cisplatin; Dexamethasone; Olanzapine; Palonosetron; Pathologic Complete Response
PubMed: 38055127
DOI: 10.1007/s10637-023-01414-y -
Farmacia Hospitalaria : Organo Oficial... 2023Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016... (Observational Study)
Observational Study
OBJECTIVE
Latest MASCC/ESMO guidelines of the recommendations for the prophylaxis of acute and delayed emesis induced by moderately emetogenic chemotherapy was published in 2016 incorporating anthracycline schemes as highly emetogenic chemotherapy (HEC), proposing triple antiemetic therapy to control nausea and vomiting. Likewise, they recommend triple therapy for carboplatin. The objectives of this study were to analyze the degree of concordance between guidelines and antiemetic prophylaxis used in the Chemotherapy Outpatient Unit in patients undergoing treatment with HEC and carboplatin, to evaluate its effectiveness and to determine the savings due to the use of netupitant/palonosetron (NEPA) oral (or) with intravenous (iv) dexamethasone (NEPAd) compared to iv Fosaprepitant with ondansetron and dexamethasone (FOD iv).
METHODS
Prospective observational study recording demographic variables, chemotherapy protocol, tumor location, patient emetogenic risk, antiemetic regimen prescribed, concordance with the MASCC/ESMO guideline, and effectiveness, evaluated by MASCC survey, use of rescue medication and visits to the Emergency Department or hospitalization due to emesis. A cost minimization pharmacoeconomic study was carried out.
RESULTS
61 patients were included; 70% women; median age 60.5. Platinum schemes were more frequent in period 1, being 87.5% compared to 67.6% in period 2. Anthracycline schemes were 21.6% and 10% respectively in each period. A 21.1% of the antiemetic regimens did not coincide with the MASCC/ESMO recommendations, being entirely in period 1. The score of the effectiveness questionnaires was total protection in 90.9% in acute nausea, from 100% in acute vomiting and delayed nausea, and 72.7% in delayed vomiting. The frequency of use of rescue medication was 18.7% in period 1 and was not necessary in period 2. No visits to the emergency room or admissions were detected in any of the periods.
CONCLUSIONS
Use of NEPAd led to a 28% reduction in costs with respect to the use of FOD. A high level of concordance was obtained in both periods between the latest published guideline and healthcare practice in our field. Surveys carried out on patients seem to suggest that both antiemetic therapies have similar effectiveness in clinical practice. The inclusion of NEPAd has led to a reduction in costs, positioning itself as an efficient option.
Topics: Female; Humans; Male; Middle Aged; Anthracyclines; Antibiotics, Antineoplastic; Antiemetics; Antineoplastic Agents; Carboplatin; Dexamethasone; Nausea; Vomiting; Prospective Studies
PubMed: 37268481
DOI: 10.1016/j.farma.2023.04.003 -
Brazilian Journal of Anesthesiology... 2024Postoperative nausea and vomiting is still a common complication. Serotonin receptor antagonists are commonly used in clinical practice for antiemetic prophylaxis.... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Postoperative nausea and vomiting is still a common complication. Serotonin receptor antagonists are commonly used in clinical practice for antiemetic prophylaxis. Interindividual variations in drug response, including single nucleotide polymorphisms, are related to pharmacokinetic and pharmacodynamic changes in these drugs and may lead to a poor therapeutic response. This study aimed to evaluate the influence of CYP2D6 isoenzyme and ABCB1 gene polymorphisms on the frequency of postoperative nausea and vomiting with the use of ondansetron or palonosetron.
METHODS
A randomized, double-blind clinical trial including 82 women aged 60 years or over undergoing laparoscopic cholecystectomy was conducted. Patients were randomized to receive either ondansetron or palonosetron for postoperative nausea and vomiting prophylaxis. DNA was extracted from saliva. Genetic polymorphisms were analyzed by real-time polymerase chain reaction. The following polymorphisms were analyzed: rs3892097 C/T, rs1128503 A/G, rs16947 A/G, rs1065852 A/G, rs1045642 A/G, rs2032582 C/A, and rs20325821 C/A.
RESULTS
Overall, vomiting, and severe nausea occurred in 22.5% and 57.5% of patients, respectively. In the palonosetron group, patients with the GG genotype (rs16947 A/G) experienced more severe nausea (p = 0.043). In the ondansetron group, patients with the AA genotype (rs16947 A/G) presented mild nausea (p = 0.034), and those with the AA genotype (rs1065852 A/G) experienced more vomiting (p = 0.034).
CONCLUSION
A low antiemetic response was observed with ondansetron in the presence of the AA genotype (rs16947 A/G) and the AA genotype (rs1065852 A/G), and a low therapeutic response was found with palonosetron in the presence of the GG genotype (rs16947 A/G) in laparoscopic cholecystectomy.
REGISTER
ClinicalTrials.gov.
Topics: Humans; Female; Postoperative Nausea and Vomiting; Cholecystectomy, Laparoscopic; Double-Blind Method; Middle Aged; Ondansetron; Antiemetics; ATP Binding Cassette Transporter, Subfamily B; Palonosetron; Aged; Cytochrome P-450 CYP2D6; Polymorphism, Single Nucleotide; Serotonin Antagonists
PubMed: 36841429
DOI: 10.1016/j.bjane.2023.02.002 -
Brazilian Journal of Anesthesiology... 2024We tested the hypothesis that, within the margin of 15% of risk difference, palonosetron is not inferior to ondansetron in reducing the incidence of postoperative nausea... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
We tested the hypothesis that, within the margin of 15% of risk difference, palonosetron is not inferior to ondansetron in reducing the incidence of postoperative nausea and vomiting (PONV) in laparoscopic cholecystectomy.
METHODS
We conducted a double-blind, non-inferiority, randomized, controlled trial of 212 patients aged 18 to 65 years undergoing laparoscopic cholecystectomy under general anesthesia in two secondary care hospitals. Patients were randomly assigned to receive either palonosetron (0.075.ßmg) or ondansetron (8.ßmg) intravenously at induction of anesthesia. Ondansetron (8.ßmg) was also administered 8 and 16.ßhours postoperatively. All anesthetic and surgical procedures were standardized. Patients were evaluated for 24.ßhours postoperatively for the occurrence of PONV.
RESULTS
A high incidence of PONV was observed at 2...6.ßhours postoperatively, with a rate of 36.8% (95% confidence interval [CI] 28.2...46.3) in the palonosetron group, as compared to 43.4% (95% CI 34.4...52.9) in the ondansetron group. The risk difference (95% CI) between palonosetron and ondansetron for PONV was 0 (-10.9 to 10.9) at 0...2.ßhours, -6.6 (-19.4 to 6.5) at 2...6.ßhours, -0.9 (-11.0 to 9.2) at 6...12.ßhours, and -2.8 (-9.6 to 3.6) at 12...24.ßhours. There was no statistically significant difference between the palonosetron and ondansetron groups in the use of rescue medication (dimenhydrinate). There were no adverse events associated with the medications under study.
CONCLUSION
Palonosetron is not inferior to ondansetron in patients at risk of PONV undergoing laparoscopic cholecystectomy, providing a good option for PONV prophylaxis, as it can be administered in a single dose.
Topics: Humans; Ondansetron; Palonosetron; Postoperative Nausea and Vomiting; Antiemetics; Cholecystectomy, Laparoscopic; Treatment Outcome; Anesthesia, General; Double-Blind Method
PubMed: 34280455
DOI: 10.1016/j.bjane.2021.06.020 -
British Journal of Cancer Feb 2024This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This study evaluated the non-inferiority of dexamethasone (DEX) on day 1, with sparing on days 2-4 in cisplatin-based chemotherapy.
METHODS
Patients with malignant solid tumors who were treated with cisplatin (≥50 mg/m²) were randomly assigned (1:1) to receive either DEX on days 1-4 (Arm D4) or DEX on day 1 (Arm D1) plus palonosetron, NK-1 RA, and olanzapine (5 mg). The primary endpoint was complete response (CR) during the delayed (24-120 h) phase. The non-inferiority margin was set at -15%.
RESULTS
A total of 281 patients were enrolled, 278 of whom were randomly assigned to Arm D4 (n = 139) or Arm D1 (n = 139). In 274 patients were included in the efficacy analysis, the rates of delayed CR in Arms D4 and D1 were 79.7% and 75.0%, respectively (risk difference -4.1%; 95% CI -14.1%-6.0%, P = 0.023). However, patients in Arm D1 had significantly lower total control rates during the delayed and overall phases, and more frequent nausea and appetite loss. There were no significant between-arm differences in the quality of life.
CONCLUSION
DEX-sparing is an alternative option for patients receiving cisplatin; however, this revised administration schedule should be applied on an individual basis after a comprehensive evaluation.
CLINICAL TRIALS REGISTRY NUMBER
UMIN000032269.
Topics: Humans; Palonosetron; Cisplatin; Neurokinin-1 Receptor Antagonists; Antiemetics; Olanzapine; Dexamethasone; Vomiting; Quality of Life; Quinuclidines; Antineoplastic Agents
PubMed: 37973958
DOI: 10.1038/s41416-023-02493-7 -
Journal of Oncology Pharmacy Practice :... Aug 2023Chemotherapy-induced nausea and vomiting (CINV) is one of the adverse events that most affects oncologic patients' quality of life. Carboplatin AUC ≥ 4 belongs to...
INTRODUCTION
Chemotherapy-induced nausea and vomiting (CINV) is one of the adverse events that most affects oncologic patients' quality of life. Carboplatin AUC ≥ 4 belongs to agents with high emetic risk (moderate risk in ASCO guidelines). We aimed to compare the effectiveness of netupitant/palonosetron and dexamethasone triple combination (TC) therapy versus ondansetron and dexamethasone double combination (DC) therapy as antiemetic prophylaxis in patients with carboplatin AUC ≥ 4. As a secondary endpoint, in TC group we evaluated the effectiveness of changing NEPA administration timing from 1 h to 15 min before chemotherapy.
METHODS
Open-label prospective study conducted in a tertiary-care hospital in patients receiving carboplatin AUC ≥ 4. CINV was evaluated using MASCC antiemetic tool, in acute (<24 h) and delayed phase (24-120 h). Results were analyzed using χ test.
RESULTS
Two-hundred four completed questionnaires (CQ) were analyzed (76 in DC and 128 in TC). The proportion of patients who remained emesis-free was superior for TC-treated group compared to DC, either in acute (99.2% vs 92.1%, = 0.0115) and delayed phase (97.6% vs 90.7%, = 0.043). Likewise, a higher proportion of TC-treated patients compared to DC remained nausea-free for the first 24 h after treatment (90.6% vs 71%, = 0.0004) and between 24 and 120 h (82.3% vs 62.7%, = 0.0025). The change of NEPA administration time showed similar effectiveness in terms of CINV control (81.6% vs 74.5%, = 0.70).
CONCLUSIONS
TC showed superiority in early and delayed CINV control in carboplatin AUC ≥ 4 regimens, with no significant differences among cancer types. Change in NEPA administration timing has beneficial implications; it allows NEPA to be administered at hospitals before chemotherapy session.
PubMed: 37563932
DOI: 10.1177/10781552231194077 -
Journal of Clinical Medicine Feb 2024Prior speculation suggests that selective 5-hydroxytryptamine-3 receptors and neurokinin-1 receptor antagonists may increase arrhythmia risk and induce...
Effect of Selective 5-Hydroxytryptamine-3 Receptor and Neurokinin-1 Receptor Antagonists on Hemodynamic Changes and Arrhythmogenic Potential in Patients Receiving Chemotherapy: A Retrospective, Observational Study.
Prior speculation suggests that selective 5-hydroxytryptamine-3 receptors and neurokinin-1 receptor antagonists may increase arrhythmia risk and induce electrocardiographic changes. This study examined the effect of anti-emetic medications on arrhythmogenic potential and hemodynamic alterations. We considered patients aged 18 or above receiving chemotherapy between June 2013 and December 2013. Patients were grouped by anti-emetic medication: intravenous granisetron (Group G), oral aprepitant plus IV granisetron (Group AG), IV palonosetron (Group P), and oral aprepitant plus IV palonosetron (Group AP). We recorded blood pressure and electrocardiography initially and at the thirtieth minute post-medication, focusing on P dispersion, QTc dispersion, and systolic/diastolic blood pressure alterations. The study included 80 patients (20 per group). Baseline systolic/diastolic blood pressure and P dispersion showed no significant variance. However, the baseline QTc dispersion was significantly lower in Groups P and AP than G and AG. The thirtieth-minute systolic/diastolic blood pressures were significantly lower than the baseline for Groups AG and AP, and the heart rates decreased in all groups. Group P showed significantly fewer blood pressure changes. We found no arrhythmogenic potential linked to granisetron, palonosetron, and aprepitant. Hypotension was more frequent at 30 min post-medication in granisetron or aprepitant recipients. Considering no hypotension occurred when using palonosetron alone, this treatment was deemed safer.
PubMed: 38337537
DOI: 10.3390/jcm13030843 -
Revista Da Associacao Medica Brasileira... 2024Anticipatory nausea and vomiting are unpleasant symptoms observed before undergoing chemotherapy sessions. Less is known about the occurrence of symptoms since the...
OBJECTIVE
Anticipatory nausea and vomiting are unpleasant symptoms observed before undergoing chemotherapy sessions. Less is known about the occurrence of symptoms since the advent of the new neurokinin-1 antagonist.
METHODS
This prospective cohort study was performed at a single Brazilian Institution. This study included breast cancer patients who received doxorubicin and cyclophosphamide chemotherapy and an appropriate antiemetic regimen (dexamethasone 10 mg, palonosetron 0.56 mg, and netupitant 300 mg in the D1 followed by dexamethasone 10 mg 12/12 h in D2 and D4). Patients used a diary to record nausea, vomiting, and use of rescue medication in the first two cycles of treatment. The prevalence of anticipatory nausea and vomiting was assessed before chemotherapy on day 1 of C2.
RESULTS
From August 4, 2020, to August 12, 2021, 60 patients were screened, and 52 patients were enrolled. The mean age was 50.8 (28-69) years, most had stage III (53.8%), and most received chemotherapy with curative intent (94%). During the first cycle, the frequency of overall nausea and vomiting was 67.31%, and that of severe nausea and vomiting (defined as grade>4 on a 10-point visual scale or use of rescue medication) was 55.77%. Ten patients had anticipatory nausea and vomiting (19.23%). The occurrence of nausea and vomiting during C1 was the only statistically significant predictor of anticipatory nausea and vomiting (OR=16, 95%CI 2.4-670.9, p=0.0003).
CONCLUSION
The prevalence of anticipatory nausea is still high in the era of neurokinin-1 antagonists, and failure of antiemetic control in C1 remains the main risk factor. All efforts should be made to control chemotherapy-induced nausea or nausea and vomiting on C1 to avoid anticipatory nausea.
Topics: Humans; Female; Breast Neoplasms; Middle Aged; Prospective Studies; Adult; Antiemetics; Aged; Nausea; Prevalence; Brazil; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Vomiting, Anticipatory; Vomiting; Dexamethasone; Palonosetron
PubMed: 38716933
DOI: 10.1590/1806-9282.20230937