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- Palonosetron versus first-generation 5-hydroxytryptamine type 3 receptor antagonists for emesis prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplantation. [JOURNAL ARTICLE]
- Ann Hematol 2014 Mar 7.
First-generation 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists (RAs) are currently the standard of care for prophylaxis against allo-HSCT-induced emesis. However, the efficacy of this combination in allo-HSCT recipients is not entirely satisfying. We sought to compare the efficacy of first-generation 5-HT3 RAs with that of second-generation 5-HT3 RAs in emesis prevention in allo-HSCT recipients. A total of 51 consecutive patients undergoing allo-HSCT for various hematological diseases in our institution were retrospectively reviewed. Patients who received daily first-generation 5-HT3 RAs, and 60-h palonosetron for emesis prophylaxis were stratified into the standard (n = 23) and palonosetron (n = 28) groups, respectively. Emesis severity and rescue therapy requirements in patients between these two groups were compared. Our results showed patients in standard and palonosetron groups had comparable severity of both acute and delayed emesis. However, 52.2 % of the patients in the standard group required rescue therapy, compared to only 21.4 % of the patients in the palonosetron group (p = 0.046). Subgroup analysis showed rescue therapy for acute emesis was required by 26.1 % of the patients in the standard group and by only 3.6 % of the patients in the palonosetron group (p = 0.037). In conclusion, palonosetron and first-generation 5-HT3 RAs were at least equally effective in emesis prophylaxis for allo-HSCT recipients. Patients receiving palonosetron, especially for acute emesis, required rescue therapy less frequently than those receiving first-generation 5-HT3 RAs.
- A randomized Phase 3 study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. [JOURNAL ARTICLE]
- Ann Oncol 2014 Mar 5.
Antiemetic guidelines recommend co-administration of agents that target multiple molecular pathways involved in emesis to maximize prevention and control of chemotherapy-induced nausea and vomiting (CINV). NEPA is a new oral fixed-dose combination of 300 mg netupitant, a highly-selective NK1 receptor antagonist (RA) and 0.50 mg palonosetron (PALO), a pharmacologically and clinically distinct 5-HT3 RA, that targets dual antiemetic pathways.This multinational, randomized, double-blind, parallel group Phase 3 study (NCT01339260) in 1455 chemotherapy-naïve patients receiving moderately emetogenic (anthracycline-cyclophosphamide) chemotherapy evaluated the efficacy and safety of a single oral dose of NEPA versus a single oral dose (0.50 mg) of PALO. All patients also received oral dexamethasone (DEX) on Day 1 only (12 mg in the NEPA arm and 20 mg in the PALO arm). The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the delayed (25-120 hr) phase in cycle 1.The percentage of patients with CR during the delayed phase was significantly higher in the NEPA group compared with the PALO group (76.9% vs. 69.5%; P=0.001), as were the percentages in the overall (0-120 hr) (74.3% vs. 66.6%; P=0.001) and acute (0-24 hr) (88.4% vs. 85.0; P=0.047) phases. NEPA was also superior to PALO during the delayed and overall phases for all secondary efficacy endpoints of no emesis, no significant nausea and complete protection (CR plus no significant nausea). NEPA was well tolerated with a similar safety profile as PALO.NEPA plus a single dose of DEX was superior to PALO plus DEX in preventing CINV following moderately emetogenic chemotherapy in acute, delayed and overall phases of observation. As a fixed-dose antiemetic drug combination, NEPA along with a single dose of dexamethasone on day 1 offers guideline-based prophylaxis with a convenient, single-day treatment.
- Safety and pharmacokinetic evaluation of repeated intravenous administration of palonosetron 0.75 mg in patients receiving highly or moderately emetogenic chemotherapy. [JOURNAL ARTICLE]
- Support Care Cancer 2014 Mar 4.
The aims of this study were to evaluate the safety, efficacy, and pharmacokinetics of repeated doses of palonosetron 0.75 mg on days 1 and 3 in Japanese patients who received highly or moderately emetogenic chemotherapy.Twenty- six patients received palonosetron 0.75 mg intravenously before chemotherapy on days 1 and 3 plus dexamethasone (12-16 mg before chemotherapy on day 1 and 4-8 mg on days 2 and 3). The primary endpoints were safety and pharmacokinetics. Pharmacokinetics were evaluated in a subset of patients (n = 6). Complete response and complete protection were evaluated as secondary endpoints.The accumulation ratios for C max and AUClast after the second dose on day 3 were 1.42 and 1.37, respectively. These values were consistent with the theoretical values expected from the half-life of palonosetron on day 1. Almost all of the patients had no nausea or vomiting in the acute phase (complete response (CR) rate, 96.2 % [25/26]; CP rate, 92.3 % [24/26]). In the delayed phase (24-192 h post-chemotherapy), the complete response and complete protection rates were 76.9 % (20/26) and 61.5 % (16/26), respectively. Treatment was well tolerated.This is the first study to report the pharmacokinetics of multiple doses of palonosetron 0.75 mg, given on days 1 and 3, in Japanese patients. Repeated treatment with palonosetron was safe and well tolerated by patients who received highly or moderately emetogenic anticancer chemotherapy.
- Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials. [JOURNAL ARTICLE]
- Support Care Cancer 2014 Mar 4.
Palonosetron, a 5-hydroxytryptamine 3 receptor antagonist (5-HT3RA) with a strong binding affinity and long half-life, has been used in numerous trials for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). We systematically reviewed the efficacy and safety of palonosetron compared to other 5-HT3RAs in CINV prophylaxis.A literature search of Ovid MEDLINE, EMBASE, and CENTRAL was conducted to identify randomized controlled trials (RCTs) comparing palonosetron to other 5-HT3RAs in CINV prophylaxis. Primary endpoints were the percentage of patients achieving a complete response (CR), complete control (CC), no emesis, no nausea, or taking no rescue medications. Secondary endpoints were the percentage of patients suffering from 5-HT3RA-related adverse events.Sixteen RCTs were identified with 2,896 patients randomized to palonosetron and 3,187 patients randomized to other 5-HT3RAs. Palonosetron was consistently statistically superior in CR, CC, no emesis, or no nausea and was sometimes superior in no rescue medication. Subgroup analyses demonstrated similarity in efficacy between highly and moderately emetogenic chemotherapy cohorts. In the acute phase, statistical superiority of palonosetron was found for trials that did not allow dexamethasone; conversely, RCTs that administered dexamethasone to all patients were nonsignificant. Palonosetron was statistically significantly safer in dizziness and mean QTc interval change and similar in constipation, headache, and diarrhea. Clinical superiority of palonosetron was reached in 3 of 19 analyzed efficacy and safety endpoints.Palonosetron is safer and more efficacious than other 5-HT3RAs. Future antiemetic guidelines should discuss the merits of including palonosetron as a first-line treatment.
- Evidence to support use of palonosetron over generic serotonin type 3-receptor antagonists for chemotherapy-induced nausea and vomiting. [Journal Article]
- Am J Health Syst Pharm 2014 Mar 1; 71(6):500-6.
- Randomized pharmacokinetic study comparing subcutaneous and intravenous palonosetron in cancer patients treated with platinum based chemotherapy. [Journal Article]
- PLoS One 2014; 9(2):e89747.
Palonosetron is a potent second generation 5- hydroxytryptamine-3 selective antagonist which can be administered by either intravenous (IV) or oral routes, but subcutaneous (SC) administration of palonosetron has never been studied, even though it could have useful clinical applications. In this study, we evaluate the bioavailability of SC palonosetron.Patients treated with platinum-based chemotherapy were randomized to receive SC or IV palonosetron, followed by the alternative route in a crossover manner, during the first two cycles of chemotherapy. Blood samples were collected at baseline and 10, 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8, 12 and 24 h after palonosetron administration. Urine was collected during 12 hours following palonosetron. We compared pharmacokinetic parameters including AUC0-24h, t1/2, and Cmax observed with each route of administration by analysis of variance (ANOVA).From October 2009 to July 2010, 25 evaluable patients were included. AUC0-24h for IV and SC palonosetron were respectively 14.1 and 12.7 ng × h/ml (p = 0.160). Bioavalability of SC palonosetron was 118% (95% IC: 69-168). Cmax was lower with SC than with IV route and was reached 15 minutes following SC administration.Palonosetron bioavailability was similar when administered by either SC or IV route. This new route of administration might be specially useful for outpatient management of emesis and for administration of oral chemotherapy.ClinicalTrials.gov NCT01046240.
- Adherence to antiemetic guidelines in patients with malignant glioma: a quality improvement project to translate evidence into practice. [JOURNAL ARTICLE]
- Support Care Cancer 2014 Feb 26.
A quality improvement project was implemented to improve adherence to evidence-based antiemetic guidelines for malignant glioma patients treated with moderately emetic chemotherapy (MEC). Poorly controlled chemotherapy-induced nausea and vomiting (CINV) reduce cancer treatment efficacy and significantly impair cancer patients' quality of life (QOL). A review of Duke University Preston Robert Tisch Brain Tumor Center (PRTBTC)'s usual practice demonstrates a high incidence (45 %) of CINV, despite premedication with short-acting 5-HT3-serotonin-receptor antagonists (5-HT3-RAs). National Comprehensive Cancer Network (NCCN)'s evidence-based guidelines recommend the combination of the long-acting 5-HT3-RA palonosetron (PAL) and dexamethasone (DEX) for the prevention of acute and delayed CINV with MEC. Low adherence (58 %) to antiemetic guidelines may have explained our high CINV incidence.One-sample binomial test, quasi-experimental design, evaluated a combination intervention that included a provider education session; implementation of risk-assessment tool with computerized, standardized antiemetic guideline order sets; and a monthly audit-feedback strategy. Post-implementation adherence to evidence-based antiemetic order sets and patient outcomes were measured and compared to baseline and historical data. Primary outcome was the guideline order set adherence rate. Secondary outcomes included nausea/vomiting rates and QOL.Adherence to ordering MEC guideline antiemetics increased significantly, from 58 % to a sustained 90 %, with associated improvement in nausea/vomiting. In acute and delayed phases, 75 and 84 % of patients, respectively, did not experience CINV. There was no significant change in QOL.Combination intervention and audit-feedback strategy to translate evidence into oncology practice improved and sustained adherence to antiemetic guidelines. Adherence corresponded with effective nausea/vomiting control and preserved QOL in patients with malignant gliomas.
- Effect of pretreatment with palonosetron on withdrawal movement associated with rocuronium injection. [Journal Article]
- Korean J Anesthesiol 2014 Jan; 66(1):23-7.
The main disadvantage of rocuronium is the pain associated with vascular injection. We evaluated the efficacy of palonosetron for reducing pain after rocuronium injection.EIGHTY PATIENTS SCHEDULED FOR ELECTIVE SURGERY WERE RANDOMLY DIVIDED INTO TWO GROUPS: Group C (normal saline 1.5 ml, n = 40) and Group P (palonosetron 0.075 mg, n = 40). Anesthesia was induced with thiopental 5 mg/kg and the test drug was injected over 10 seconds. Thirty seconds after the injection of the test drug, rocuronium 0.6 mg/kg was injected over 30 seconds and the response was recorded. Injection pain was graded using a 4-point scale. The grade was 0 points for no movement, 1 point for wrist movement, 2 points for elbow or shoulder movement, and 3 points for whole body movement. Mean arterial pressure and heart rate were recorded on arrival in the operating room and before and 30 seconds after rocuronim injection.There was no significant difference in the grade 1 response between the two groups; however, the grade 2 and 3 responses in Group P were 5 (12.5%) and 4 (10%), respectively, which were significantly lower than in Group C, with 13 (32.5%) responses for each grade. There were no significant differences in hemodynamic changes within each group. However, the difference in mean arterial pressure before and after the injection of rocuronium was significantly larger in Group C compared to Group P.Pretreatment with palonosetron 0.075 mg reduced the incidence and severity of withdrawal movement after rocuronium administration.
- Two birds with one stone: palonosetron pretreatment. [Journal Article]
- Korean J Anesthesiol 2014 Jan; 66(1):1-2.
- IgE-mediated hypersensitivity to ondansetron and safe use of palonosetron. [Journal Article]
- J Allergy Clin Immunol Pract 2013 Sep-Oct; 1(5):526-7.