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- A prospective, randomized, double-blind, multicenter trial to evaluate the therapeutic efficacy and safety of palonosetron in the treatment of postoperative nausea and vomiting over a 72-h period. [JOURNAL ARTICLE]
- J Anesth 2014 Jul 19.
We performed a multicenter, randomized, double-blind trial to assess the efficacy and safety of a single, fixed, intravenous dose of palonosetron (0.075 mg) in the treatment of established postoperative nausea and vomiting (PONV).Three hundred and eighty-four patients who had at least one risk factors of PONV and underwent surgery under general anesthesia were screened. Those who developed PONV were randomized to receive either 0.075 mg intravenous palonosetron or a placebo. The incidence of nausea and vomiting, severity of nausea, requirements for rescue anti-emetics, and adverse effects at 2, 24, and 72 h after drug administration were evaluated. Complete response (CR) and complete control (CC) rate were compared for 24 and 72 h.Among the 384 patients, 152 (39.6 %) developed PONV and were randomized to either the palonosetron (n = 75) or placebo (n = 77) group. The number of patients with CR at 24 and 72 h was higher in the palonosetron group than the placebo group [0-24 h: n = 49 (68.1 %) vs. n = 30 (40.5 %), p < 0.001; 0-72 h: n = 47 (65.3 %) vs. n = 28 (37.8 %), p < 0.001]. The incidence of PONV at 2, 24, and 72 h periods was lower in the palonosetron group than the placebo group (29.2, 45.8, and 50.0 % in the palonosetron group vs. 50.0, 62.2, and 66.2 % in the placebo group, p = 0.010, 0.048, 0.047, respectively). The incidence of adverse events was not different between the groups.A single 0.075 mg IV dose of palonosetron effectively increased the CR rates at 24 and 72 h in these moderate-risk patients with established PONV.
- Multicenter nonrandomized trial of ramosetron versus palonosetron in controlling chemotherapy-induced nausea and vomiting for colorectal cancer. [Journal Article]
- Ann Surg Treat Res 2014 Jul; 87(1):9-13.
Chemotherapy-induced nausea and vomiting (CINV) have a negative impact on patients' quality of life and frequently pointed to as a major factor for treatment abandonment. Serotonin (5-HT3) receptor antagonist is considered as key treatment for CINV. Ramosetron and palonosetron are recently developed 5-HT3 receptor antagonists and known as more superior than other first-generation 5-HT3 receptor antagonists. The purpose of this study was to compare the efficacy of ramosetron and palonosetron and determine which drug is more effective for prevention of CINV.Colorectal cancer patients treated with chemotherapy were enrolled consecutively. Patients were assigned to receive intravenous injection of ramosetron 0.3 mg or palonosetron 0.25 mg at 30 minutes before initiation of moderately emetogenic chemotherapy. Ramosetron group added oral administration of 0.1 mg ramosetron on the second and third days of chemotherapy. Efficacy parameter consisted of nausea and vomiting.Ninety-one patients received ramosetron and 89 patients received palonosetron. Presentation of vomiting and nausea symptoms was not significantly different between the two groups during acute (0-24 hours) and delayed period (after 24 hours).The incidence of CINV between the ramosetron and the palonosetron group has not shown any difference during acute, delayed, and overall period.
- The Impact of 5-HT3RA Use on Cost and Utilization in Patients with Chemotherapy-Induced Nausea and Vomiting: Systematic Review of the Literature. [Journal Article, Review]
- Am Health Drug Benefits 2014 May; 7(3):171-82.
Individual studies have assessed the impact of standard prophylactic therapy with 5-hydroxytryptamine receptor antagonists (5-HT3RAs) for chemotherapy-induced nausea and vomiting (CINV) on cost and utilization, but no synthesis of the findings exists.To systematically review published literature on costs and utilization associated with CINV prophylaxis with palonosetron and other 5-HT3RAs.PubMed and the National Institute for Health Research Centre for Reviews and Dissemination databases, conferences of 4 organizations (ie, Academy of Managed Care Pharmacy, American Society of Clinical Oncology, International Society for Pharmacoeconomics and Outcomes Research, and Multinational Association of Supportive Care in Cancer), and the bibliographies of relevant articles were queried for the medical subject headings and key terms of "ondansetron," "granisetron," "palonosetron," "dolasetron mesylate," "costs," "cost analysis," and "economics." We included records published (full-length articles after 1997 and conference presentations after 2010) in English and with human patients, reporting data on cost and utilization (rescue medication, outpatient and inpatient services) associated with the use of 5-HT3RAs for the treatment or prevention of CINV.Of the 434 identified studies, 32 are included in the current analysis: 7 studies report costs, 18 report utilization, and 7 studies report both. The costs are reported in US dollars (7 studies), in Euros (5 studies), and in Canadian dollars (2 studies). The studies vary in designs, patients, 5-HT3RA regimens, and the definition of outcomes. The US studies report higher drug costs for CINV prophylaxis with palonosetron compared with ondansetron, lower medical outpatient and inpatient costs for palonosetron versus other 5-HT3RAs, and higher acquisition costs for palonosetron versus ondansetron or other 5-HT3RAs. Fewer patients receiving palonosetron versus with ondansetron or other 5-HT3RAs required rescue medication or used outpatient or inpatient care. In Europe and in Canada, the total pharmacy costs and use of rescue medications reported are lower for patients receiving prophylaxis with palonosetron.This analysis shows that prophylaxis with palonosetron for the treatment of CINV is associated with higher acquisition treatment costs, but also with lower use of rescue medications and outpatient and inpatient services compared with ondansetron or other 5-HT3RAs in the United States. Therefore, the use of palonosetron as a standard treatment may lead to reduced service utilization for CINV.
- Outcomes Associated with 5-HT3-RA Therapy Selection in Patients with Chemotherapy-Induced Nausea and Vomiting: A Retrospective Claims Analysis. [Journal Article]
- Am Health Drug Benefits 2014 Jan; 7(1):50-8.
Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of chemotherapy, and may present during the administration of chemotherapy (ie, acute CINV) or within 25 to 120 hours of chemotherapy (ie, delayed CINV). Preventing CINV with the initiation of chemotherapy is important, because the risk for CINV in future chemotherapy cycles increases if CINV occurs in the first or previous treatment cycle. Inadequately controlled CINV is associated with increased resource utilization and costs, particularly for patients receiving highly or moderately emetogenic chemotherapy.To evaluate the clinical and economic impacts of delayed CINV events in patients who receive initial and maintenance therapy with the newer-generation 5-hydroxytryptamine3 receptor antagonist (5-HT3-RA) palonosetron compared with patients who receive initial and maintenance therapy with an older 5-HT3-RA agent.A retrospective database analysis was conducted using the OptumInsight database covering the years 2005-2011 (96% commercially insured members, 4% Medicaid members). Patients with cancer who received initial therapy with an emetogenic single-day chemotherapy regimen and a 5-HT3-RA agent (ie, dolasetron, granisetron, ondansetron, or palonosetron) were included in the analysis. The outcomes measured included the overall rates of delayed CINV for cycles 1 to 6, by 5-HT3-RA cohort. For cycles 2 to 6, calculations were based on patients who experienced CINV in the previous cycle, maintained the same 5-HT3-RA for all cycles, and had chemotherapy with a similar level of emetic potential. The economic outcomes (ie, cost and utilization) were also collected and calculated.A total of 26,974 patients were included in the analysis. The overall rate for delayed CINV at cycle 1 was 15.6%, and the lowest rate was for palonosetron at 15%. The patients who initiated palonosetron had lower CINV rates throughout all cycles. The regression analysis compared individual agents to palonosetron and demonstrated higher odds of CINV in the second cycle for the older agents (ondansetron: odds ratio [OR], 1.41; 95% confidence interval [CI], 1.14-1.74; P <.002; granisetron: OR, 1.70; 95% CI, 1.39-2.08; P <.001; dolasetron: OR, 1.65; 95% CI, 1.27-2.15; P = .002). This trend continued through cycle 6, and not all ORs were significant. Over 6 cycles, ondansetron cost an additional $126,775 compared with palonosetron; granisetron an additional $169,838 versus palonosetron; and dolasetron an additional $148,960.Current guidelines support the use of 5-HT3-RA agents for the prevention of CINV. As shown in this analysis, the selection of a specific 5-HT3-RA agent has a clinical and subsequent economic impact on patients with cancer experiencing delayed CINV. Specifically, patients receiving therapy with palonosetron had a lower incidence of delayed CINV and incurred lower overall costs.
- Netupitant and palonosetron trigger NK1 receptor internalization in NG108-15 cells. [JOURNAL ARTICLE]
- Exp Brain Res 2014 Jun 27.
Current therapy for chemotherapy-induced nausea and vomiting includes the use of both 5-HT3 and NK1 receptor antagonists. Acute emesis has largely been alleviated with the use of 5-HT3 receptor antagonists, while an improvement in preventing delayed emesis has been achieved with NK1 receptor antagonists. Delayed emesis, however, remains a problem with a significant portion of cancer patients receiving highly emetogenic chemotherapy. Like other drugs in its class, palonosetron, a 5-HT3 receptor antagonist, has shown efficacy against acute emesis. However, palonosetron has also shown consistent improvement in the suppression of delayed emesis. Since both 5-HT3 and NK1 receptor antagonists are often simultaneously administered to patients, the question remains if palonosetron's effect on delayed emesis would remain distinct when co-administered with an NK1 receptor antagonist. Recent mechanistic studies using NG108-15 cells have shown that palonosetron and netupitant, an NK1 receptor antagonist currently in phase 3 clinical trials, exhibited synergistic effects when inhibiting the substance P response. The present studies showed that both netupitant and palonosetron-induced NK1 receptor internalization in NG108-15 cells and that when used together receptor internalization was additive. Palonosetron-induced NK1 receptor internalization was dependent on the presence of the 5-HT3 receptor. Results provide a possible explanation for palonosetron's enhancement of the inhibition of the SP response and suggest that the effect of palonosetron and NK1 receptor antagonists on prevention of delayed emesis could be additive.
- Evaluation of an every-other-day palonosetron schedule to control emesis in multiple-day high-dose chemotherapy. [JOURNAL ARTICLE]
- Future Oncol 2014 Jun 20.:1-10.
ABSTRACT Aim: Efficacy of intermittent palonosetron dosing in patients undergoing multiple-day, high-dose chemotherapy (HDC) was investigated. Patients & methods: Fifty-eight patients received palonosetron (0.25 mg intravenous [iv.]) every other day plus daily dexamethasone (8 mg iv. twice daily) dosing. The primary end point was complete control (CC; no emesis, no rescue anti-emetics, and no more than mild nausea) in the overall acute-period (until 24 h after chemotherapy completion). Results: Acute-period CC occurred in 81% and 50% of patients receiving palonosetron and ondansetron (historical control cohort), respectively. Palonosetron (odds ratio [OR]: 4.37; p = 0.001) and a longer duration of HDC regimen (OR: 3.47; p = 0.011) independently predicted a better anti-emetic outcome. Conclusion: Palonosetron every other day plus daily dexamethasone is an effective anti-emetic coverage in patients undergoing HDC.
- Comparative HPLC enantioseparation on substituted phenylcarbamoylated cyclodextrin chiral stationary phases and mobile phase effects. [JOURNAL ARTICLE]
- J Pharm Biomed Anal 2014 May 29.:221-227.
Two new cyclodextrin-derived chiral stationary phases with multiple urea linkages were prepared through the Staudinger reactions between aminopropyl silica gel and cyclodextrin derivatives, namely, heptakis(6-azido-6-deoxy-2,3-di-O-3,5-dimethylphenylcarbamoylated)-β-cyclodextrin and heptakis(6-azido-6-deoxy-2,3-di-O-3,5-dichlorophenylcarbamoylated)-β-cyclodextrin, respectively. HPLC separation behaviors toward 46 chiral analytes have been investigated under multimodal elution. They exhibited good separation performances for these analytes and also showed some complimentary enantioselectivity to each other, due to different electron-donating (methyl)/withdrawing (chlorine) groups in the phenylcarbamate moieties. Among these analytes, aromatic alcohols and N-(2,4-dinitrophenyl)-derived carboxylic acids were better resolved on the π-basic chiral stationary phase than the π-acidic. The proton pump inhibitors, the 5-hydroxytryptamine receptor antagonists, and the analytes with carbonyl groups easily formed stereoselective interactions with the π-acidic chiral stationary phase, further leading to better enantioseparation. Elution order reversal for palonosetron and N-(2,4-dinitrophenyl) glutamine was observed in three chiral stationary phases, probably induced by the difference of phenylcarbamate groups. Moreover, mobile phase effects on retention behaviors of analytes have been studied in detail.
- Phase II Study on EANI Combined with Hydrochloride Palonosetron for Prevention of Chemotherapy-induced Nausea and Vomiting Following Highly Emetogenic Chemotherapy. [Journal Article]
- Asian Pac J Cancer Prev 2014; 15(9):3951-4.