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Advances in Therapy Jul 2023Chemotherapy-induced nausea and vomiting (CINV) is a recognized adverse outcome among patients with cancer. This retrospective study aimed to quantify the treatment...
INTRODUCTION
Chemotherapy-induced nausea and vomiting (CINV) is a recognized adverse outcome among patients with cancer. This retrospective study aimed to quantify the treatment outcomes, resource utilization, and costs associated with antiemetic use to prevent CINV in a broad US population who received cisplatin-based chemotherapy.
METHODS
Data from the STATinMED RWD Insights Database was collected from January 1, 2015 to December 31, 2020. Cohorts included any patients that had at least one claim for fosnetupitant + palonosetron (NEPA) or fosaprepitant + palonosetron (APPA) and evidence of initiating cisplatin-based chemotherapy. Logistic regression was used to evaluate nausea and vomiting visits within 14 days after chemotherapy, and generalized linear models were used to examine all-cause and CINV-related healthcare resource utilization (HCRU) and costs.
RESULTS
NEPA was associated with significantly lower rates of nausea and vomiting visits after chemotherapy (p = 0.0001), including 86% greater odds of nausea and vomiting events for APPA during the second week after chemotherapy (odds ratio [OR] = 1.86; p = 0.0003). The mean numbers of all-cause inpatient visits (p = 0.0195) and CINV-related inpatient and outpatient visits were lower among NEPA patients (p < 0.0001). These differences corresponded to 57% of NEPA patients and 67% of APPA patients having one or more inpatient visits (p = 0.0002). All-cause outpatient costs and CINV-related inpatient costs were also significantly lower for NEPA (p < 0.0001). The mean number of all-cause outpatient visits, all-cause inpatient costs, and CINV-related outpatient costs was not significantly different between groups (p > 0.05).
CONCLUSION
In this retrospective study based on claims data, NEPA was associated with lower rates of nausea and vomiting and lower CINV-related HCRU and costs compared to APPA following cisplatin-based chemotherapy. These results complement clinical trial data and published economic models supporting the use of NEPA as a safe, effective, and cost-saving antiemetic for patients undergoing chemotherapy.
Topics: Humans; Antiemetics; Cisplatin; Palonosetron; Retrospective Studies; Nausea; Vomiting; Neoplasms; Quinuclidines; Treatment Outcome; Gastrointestinal Agents; Delivery of Health Care; Antineoplastic Agents
PubMed: 37245189
DOI: 10.1007/s12325-023-02537-7 -
Minerva Anestesiologica Jun 2023Genetic variants may affect drug efficacy on postoperative nausea and vomiting (PONV). The understanding of these mechanisms will help to identify the surgical patients... (Review)
Review
INTRODUCTION
Genetic variants may affect drug efficacy on postoperative nausea and vomiting (PONV). The understanding of these mechanisms will help to identify the surgical patients who might benefit from specific prophylactic and therapeutic antiemetic treatment. The aim of the present review was to investigate gene polymorphisms that influence 5-hydroxytryptamine (serotonin) type 3 receptor antagonists (5HT3RA) efficacy in PONV.
EVIDENCE AQUISITION
We included articles published from 2005 to 2022, utilizing the electronic databases PUBMED, EMBASE, COHRANE Library and ScienceDirect. To explore the relationship between genetic variations and 5HT3 receptor antagonist efficacy in PONV we focused on three different gene polymorphisms: the cytochrome P450 mono-oxygenase system gene (CYP2D6), the adenosine triphosphate (ATP)-binding cassette subfamily B gene (ABCB1) as well as the 5HT3 receptor gene (5HT3R). We also explored the relationship between the above genetic variations and their impact on 5HT3RA efficacy in the context of chemotherapy induced nausea and vomiting.
EVIDENCE SYNTHESIS
Our search retrieved a total of 70 articles; 29 of them were included in the present review. Regarding polymorphisms of the CYP2D6 gene and the efficacy of serotonin antagonists in PONV, the ultra-rapid metabolizer genotype was associated with reduced efficacy of ondansetron, dolasetron and tropisetron, with the latter presenting more pronounced failure in these patients, while granisetron's efficacy remained unaffected. Regarding variations in the ABCB1 gene, three polymorphisms ("2677G>T/A" in exon 21; "3435C>T" in exon 27; "C1236T" in exon 12) were associated with a better response to ondansetron and ramosetron, while they did not affect palonosetron's efficacy. Additionally, polymporphisms of the 5-HT3B receptor gene were associated with ondancetron's postoperative efficacy; the "100_-102AAG" deletion variant was associated with reduced efficacy, while the Y129S variant did not show any effect on the drug's antiemetic effect.
CONCLUSIONS
This review highlights that inefficacy of a specific drug in managing PONV could be attributed to specific genetic profiles and patients would possibly benefit from a drug switch.
Topics: Humans; Postoperative Nausea and Vomiting; Ondansetron; Pharmacogenetics; Cytochrome P-450 CYP2D6; Antiemetics
PubMed: 36852569
DOI: 10.23736/S0375-9393.22.16983-X -
Cureus Sep 2022Background Female gender, young age, first chemotherapy cycle, and low alcohol intake have all been linked to an increased risk of nausea and vomiting from chemotherapy....
The Effectiveness of an Oral Fixed-Dose Combination of Netupitant and Palonosetron (NEPA) in Patients With Multiple Risk Factors for Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Observational Indian Study.
Background Female gender, young age, first chemotherapy cycle, and low alcohol intake have all been linked to an increased risk of nausea and vomiting from chemotherapy. We intended to see if netupitant and palonosetron (NEPA) could prevent chemotherapy-induced nausea and vomiting (CINV) in patients with risk factors such as age, gender, chemotherapy cycle number, and alcohol consumption history. Methods In this retrospective study, chemotherapy-naïve patients who were prescribed netupitant (300 mg) and palonosetron (0.50 mg) (NEPA) before the first cycle of chemotherapy were analyzed for overall, acute, and delayed phases of complete response (CR), complete protection (CP), and control. Results In the acute phase (AP), delayed phase (DP), and overall phase (OP), complete response was 88.23%, 86.27%, and 86.27%, respectively; complete protection was 80.39%, 78.43%, and 76.47%, respectively; and complete control was 76.47%, 72.54%, and 70.58%, respectively, in the whole population (i.e., 51 patients). Complete response, protection, and control in the overall phase were achieved by 86.27%, 72.72%, and 68.18% of patients who received the highly emetogenic chemotherapy (HEC) regimen (i.e., 44 patients), respectively. Conclusion NEPA provided a consistent magnitude of benefit for patients who are at high risk, receiving HEC and moderately emetogenic chemotherapy (MEC), and having good control in the acute, delayed, and overall phases of CINV.
PubMed: 36259011
DOI: 10.7759/cureus.29094 -
Future Oncology (London, England) Sep 2022To further evaluate the antiemetic efficacy of single-dose versus multiple-dose dexamethasone (DEX) against nausea and vomiting caused by cisplatin. Two similar... (Randomized Controlled Trial)
Randomized Controlled Trial
To further evaluate the antiemetic efficacy of single-dose versus multiple-dose dexamethasone (DEX) against nausea and vomiting caused by cisplatin. Two similar non-inferiority studies were pooled. Patients were randomized to single-day DEX or multiple-day DEX plus palonosetron and neurokinin-1 receptor-antagonists (NK-1RAs). The primary endpoint was complete response (CR; no vomiting and no rescue medication) during the overall phase. The combined analysis included 242 patients. The absolute risk difference between single day versus multi-day DEX for CR was -2% (95% CI, -14 to 9%). Administration of single-dose DEX offers comparable antiemetic control to multiple-day DEX when combined with palonosetron and an NK-1RA in the setting of single-day cisplatin.
Topics: Humans; Palonosetron; Antiemetics; Cisplatin; Quinuclidines; Isoquinolines; Dexamethasone; Antineoplastic Agents; Vomiting
PubMed: 36017782
DOI: 10.2217/fon-2022-0330 -
Supportive Care in Cancer : Official... Aug 2021Palonosetron, a long-acting 5-HT receptor antagonist, is an effective antiemetic agent for chemotherapy-induced nausea and vomiting; however, it sometimes causes severe...
PURPOSE
Palonosetron, a long-acting 5-HT receptor antagonist, is an effective antiemetic agent for chemotherapy-induced nausea and vomiting; however, it sometimes causes severe constipation. The aim of the present study was to evaluate the severity of palonosetron-related constipation.
METHODS
We retrospectively analyzed the incidence and severity of constipation after intravenous administration of 0.75-mg palonosetron in 150 chemotherapy-naïve patients who received first-line chemotherapy at Saga University Hospital. Constipation was classified into grades 1-5 according to the Common Terminology Criteria for Adverse Events version 5.0. Multiple logistic regression analysis was performed to identify factors associated with palonosetron-related worsening of constipation to grade 2 or higher.
RESULTS
Palonosetron significantly increased the incidence and severity of constipation (incidence: before vs. after palonosetron, 35.4% vs. 74.0%, p < 0.0001, and severity: before vs. after palonosetron, 26.7% and 8.7% in grades 1 and 2, respectively, vs. 46.7%, 23.3%, and 4.0% in grades 1, 2, and 3, respectively, p < 0.0001). Despite the use of laxatives, 4.0% of patients had grade 3 constipation requiring manual evacuation. Combination treatment with aprepitant (odds ratio (OR), 10.9; 95% confidence interval (CI), 1.3-90.0; p = 0.026) and older age (OR, 1.25; 95% CI, 1.01-1.57; p = 0.039) were factors associated with the severity of constipation.
CONCLUSION
Constipation was more severe in patients receiving combination treatment with aprepitant than in those treated with palonosetron alone. Older age was also associated with increased risk of severe palonosetron-related constipation. Identification of risk factors can help target risk-based laxative therapy.
Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Constipation; Female; Humans; Male; Middle Aged; Palonosetron; Retrospective Studies; Young Adult
PubMed: 33515108
DOI: 10.1007/s00520-021-06023-0 -
Anesthesia and Pain Medicine Jan 2020We compared the effects of palonosetron with ondansetron for preventing postoperative nausea and vomiting (PONV) during the first 24 h after surgery in women receiving...
BACKGROUND
We compared the effects of palonosetron with ondansetron for preventing postoperative nausea and vomiting (PONV) during the first 24 h after surgery in women receiving intravenous patient-controlled analgesia (IV-PCA) with fentanyl for pain control.
METHODS
In this prospective, randomized, double-blinded study, 204 healthy patients who were undergoing elective surgery with general anesthesia were enrolled. In the palonosetron group (n = 102), 0.075 mg bolus was given intravenously (i.v.) 30 min before the end of surgery and 8 ml saline was added to the IV-PCA. In the ondansetron group (n = 102), 8 mg bolus i.v. was given 30 min before the end of surgery and 16 mg of ondansetron was added to the IV-PCA. The incidence of PONV, severity of nausea, and use of rescue anti-emetics were evaluated 6 and 24 h after the operation.
RESULTS
The incidences of nausea (55.6%) and vomiting (14.1%) in the palonosetron group did not differ from those (58.3 and 19.8%) in the ondansetron group during the first 24 h after surgery (P > 0.05). No significant differences were observed in the severity of nausea and use of rescue anti-emetics between the two groups (P > 0.05).
CONCLUSIONS
The effects of palonosetron in preventing PONV were not different from those of ondansetron during the first 24 h postoperatively in women receiving IV-PCA with fentanyl.
PubMed: 33329786
DOI: 10.17085/apm.2020.15.1.28 -
Medicine Aug 2021Postoperative nausea and vomiting (PONV) is an undesirable complication in patients undergoing general anesthesia. Combination therapy via different mechanisms of action...
BACKGROUND
Postoperative nausea and vomiting (PONV) is an undesirable complication in patients undergoing general anesthesia. Combination therapy via different mechanisms of action for antiemetic prophylaxis has been warranted for effective treatment of PONV. This study was designed to compare the prophylactic antiemetic effect between midazolam combined with palonosetron (group MP) and palonosetron alone (group P) after laparoscopic cholecystectomy surgeries.
METHODS
A prospective randomized controlled trial was investigated in non-smoking female. Eighty-eight patients were randomly divided into 2 groups with 44 patients each. Group MP received 0.05 mg/kg of midazolam intravenously before induction of anesthesia whereas group P received the same volume of normal saline. Immediately after anesthetic induction, 0.075 mg of palonosetron was administered to both the groups. The incidence and severity of PONV were assessed during 2 time intervals (0-2 hours, 2-24 hours), postoperatively.
RESULTS
The incidence of PONV during 24 hours after surgery was lower in group MP as compared to group P. There was also a significant difference in the use of rescue antiemetics. The severity of nausea was significantly lower in group MP as compared to group P, in the initial 2 hours after surgery. The incidence of side effects was similar between the 2 groups.
CONCLUSION
In the prevention of PONV, midazolam combined with palonosetron, administered during induction of anesthesia was more effective as compared to palonosetron alone.
Topics: Adjuvants, Anesthesia; Adult; Antiemetics; Cholecystectomy, Laparoscopic; Female; Humans; Male; Midazolam; Middle Aged; Palonosetron; Postoperative Nausea and Vomiting; Prospective Studies; Republic of Korea
PubMed: 34414984
DOI: 10.1097/MD.0000000000026997 -
Cancer Chemotherapy and Pharmacology Jul 2021Chemotherapy-induced nausea and vomiting (CINV) is considered one of the most serious adverse events affecting chemotherapy-receiving cancer patients. It dramatically... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of clinical outcomes and efficacy of palonosetron and granisetron in combination with dexamethasone in Egyptian patients receiving highly emetogenic chemotherapy.
BACKGROUND
Chemotherapy-induced nausea and vomiting (CINV) is considered one of the most serious adverse events affecting chemotherapy-receiving cancer patients. It dramatically affects their food intake, nutritional status and more importantly their quality of life. We can observe CINV in highly emetogenic chemotherapy (HEC) such as adriamycin-cyclophosphamide combination (AC) in breast cancer patients and cisplatin-based regimens in other cancer types. This study aimed to evaluate the antiemetic efficacy of palonosetron (PALO) over granisetron (GRA) in combination with dexamethasone for multiple highly emetogenic chemotherapy drugs (HEC), especially in chemotherapy regimens in Egyptian breast cancer patients and cisplatin-based regimens in other diseases.
PATIENTS AND METHODS
An open-label randomized trial was carried out, including 115 patients receiving at least four cycles of highly emetogenic chemotherapy regimens. All patients received dexamethasone in combination with the 5-HT3 receptor antagonist. We recorded patients' clinical and biochemical characteristics and withdraw blood samples to monitor serum substance P and serotonin in correlation with chemotherapy-induced nausea and vomiting (CINV). We use the MASCC antiemetic tool in the acute phase (0-24 hr) and delayed phase (24-120 h) to evaluate patient outcomes in both stages after each chemotherapy cycle.
RESULTS
In (PALO) group, only 7.84% of patients showed acute vomiting, and 11.76% showed acute nausea, whereas 43.75% of patients showed acute vomiting and 89.06% showed acute nausea in (GRA) group (P < 0.0001). For delayed CINV, 23.53% of patients showed delayed vomiting, and 47.06% showed delayed nausea in the (PALO) group, while 82.81% of patients showed delayed emesis, and 92.19% showed delayed nausea in (GRA) group (P < 0.0001). The study showed that PALO is a cost-effective choice when compared to GRA in CINV prevention as 45.10% of patients in (PALO) required additional rescue medications (Domperidone 10 mg orally three times per day plus Trimebutine 200 mg orally three times per week both for 5 days), while 95.24% in the (GRA) group used the same medications. Adverse events of both antiemetic drugs (PALO and GRA) include headaches and constipation and QTc prolongation reports, mostly mild to moderate, with relatively low rates among the two groups.
CONCLUSION
Palonosetron, combined with dexamethasone, is more effective than granisetron and dexamethasone combination against both acute and delayed emesis induced by highly emetogenic chemotherapy (HEC) cisplatin-based protocols and the combination of cyclophosphamide and anthracyclines (AC). Medical team members should make more efforts, especially clinical pharmacy personnel, to monitor medications' effectiveness and help the medical team achieve a suitable and reliable care plan.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Egypt; Female; Granisetron; Humans; Male; Middle Aged; Nausea; Palonosetron; Quality of Life; Vomiting
PubMed: 33835230
DOI: 10.1007/s00280-021-04257-7 -
Brazilian Journal of Anesthesiology... 2024End-stage renal diseases patients have a high risk of postoperative nausea and vomiting (PONV), which is multifactorial and need acute attention after renal... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
End-stage renal diseases patients have a high risk of postoperative nausea and vomiting (PONV), which is multifactorial and need acute attention after renal transplantation for a successful outcome in term of an uneventful postoperative period. The study was done to compare the efficacy of palonosetron and ondansetron in preventing early and late-onset PONV in live donor renal transplantation recipients (LDRT).
METHODS
The prospective randomized double-blinded study was done on 112 consecutive patients planned for live donor renal transplantation. Patients of both sexes in the age group of 18...60 years were randomly divided into two groups: Group O (Ondansetron) and Group P (Palonosetron) with 56 patients in each group by computer-generated randomization. The study drug was administered intravenously (IV) slowly over 30.ßseconds, one hour before extubation. Postoperatively, the patients were accessed for PONV at 6, 24, and 72.ßhours using the Visual Analogue Scale (VAS) nausea score and PONV intensity scale.
RESULTS
The incidence of PONV in the study was found to be 30.35%. There was significant difference in incidence of PONV between Group P and Group O at 6.ßhours (12.5% vs. 32.1%, p.ß=.ß0.013) and 72.ßhours (1.8% vs. 33.9%, p.ß<.ß0.001), but insignificant difference at 24.ßhours (1.8% vs. 10.7%, p.ß=.ß0.113). VAS-nausea score was significantly lower in Group P as compared to Group O at a time point of 24.ßhours (45.54.ß...ß12.64 vs. 51.96.ß...ß14.70, p.ß=.ß0.015) and 72.ßhours (39.11.ß...ß10.32 vs. 45.7.ß...ß15.12, p.ß=.ß0.015).
CONCLUSION
Palonosetron is clinically superior to ondansetron in preventing early and delayed onset postoperative nausea and vomiting in live-related renal transplant recipients.
Topics: Male; Female; Humans; Adolescent; Palonosetron; Ondansetron; Postoperative Nausea and Vomiting; Antiemetics; Kidney Transplantation; Prospective Studies; Double-Blind Method
PubMed: 34411635
DOI: 10.1016/j.bjane.2021.07.027 -
Supportive Care in Cancer : Official... Nov 2022The aim of this study was to assess the cost-effectiveness of NEPA, a fixed-dose combination of oral netupitant (300 mg) and palonosetron (0.5 mg), compared to...
Cost-effectiveness analysis of NEPA, a fixed-dose combination of netupitant and palonosetron, for the prevention of highly emetogenic chemotherapy-induced nausea and vomiting: an international perspective.
PURPOSE
The aim of this study was to assess the cost-effectiveness of NEPA, a fixed-dose combination of oral netupitant (300 mg) and palonosetron (0.5 mg), compared to available treatments in Spain after aprepitant generic introduction in the market, and to discuss results in previously performed analyses in different wordwide settings.
METHODS
A Markov model including three health states, complete protection, complete response at best and incomplete response, was used to evaluate the cost-effectiveness of NEPA versus common treatment options in Spain during 5 days after chemotherapy. Incremental costs including treatment costs and treatment failure management cost as well as incremental effects including quality adjusted life days (QALDs) and emesis-free days were compared between NEPA and the comparator arms. The primary outcomes were cost per avoided emetic event and cost per QALDs gained.
RESULTS
NEPA was dominant (more effective and less costly) against aprepitant combined with palonosetron, and fosaprepitant combined with granisetron, while, compared to generic aprepitant plus ondansetron, NEPA showed an incremental cost per avoided emetic event of €33 and cost per QALD gained of €125.
CONCLUSION
By most evaluations, NEPA is a dominant or cost-effective treatment alternative to current antiemetic standards of care in Spain during the first 5 days of chemotherapy treatment in cancer patients, despite the introduction of generics. These results are in line with previously reported analyses throughout different international settings.
Topics: Humans; Palonosetron; Cost-Benefit Analysis; Aprepitant; Emetics; Vomiting; Antineoplastic Agents; Nausea; Antiemetics; Internationality; Quinuclidines
PubMed: 36074186
DOI: 10.1007/s00520-022-07339-1