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- WITHDRAWN: Serotonin receptor antagonists for highly emetogenic chemotherapy in adults. [JOURNAL ARTICLE]
- Cochrane Database Syst Rev 2013 Dec 9.:CD006272.
Serotonin receptor antagonists (5-HT3 RAs) are used to control chemotherapy-induced emesis. Although they have the same general mechanism of action (blockade of serotonin receptors), they have different chemical structures and may have different effects.To compare efficacy of different serotonin receptor antagonists (5-HT3 RAs) in the control of acute and delayed emesis induced by highly emetogenic chemotherapy.We searched CENTRAL, the Specialised Register of the Cochrane PaPaS Group, PubMed, EMBASE, and LILACS databases. Our most recent search was in March 2009.Randomised trials comparing 5-HT3 RAs in an adult cancer population.We extracted information from the included studies on the control of acute and delayed nausea and vomiting, either as a single or a combined outcome. Where appropriate, we combined the results of similar trials. We carried out sensitivity and subgroup analyses to test the robustness of our findings.We included 16 randomised trials (7808 participants). Nine of the trials compared granisetron versus ondansetron. No other drug comparison was studied in more than one trial. The meta-analyses of the granisetron versus ondansetron trials found similar results for the two drugs on acute vomiting (eight trials, 4256 participants, odds ratio (OR) 0.89; 95% CI 0.78 to 1.02), acute nausea (seven trials, 4160 participants, OR 0.97; 95% CI 0.85 to 1.10), delayed vomiting (three trials, 1119 participants, OR 1.00; 95% CI 0.74 to 1.34) and delayed nausea (two trials, 1024 participants, OR 0.96; 95% CI 0.75 to 1.24). Granisetron and ondansetron showed similar effects on headache and diarrhoea, with the possible exception of less constipation associated with ondansetron.One study of 1114 participants comparing palonosetron plus dexamethasone versus granisetron plus dexamethasone showed superiority of palonosetron in controlling delayed vomiting (OR 1.45; 95% CI 1.14 to 1.85) and delayed nausea (OR 1.63; 95% CI 1.27 to 2.10). Complete response for delayed nausea and vomiting was also in favour of the combination palonosetron and dexamethasone (OR 1.63; 95% CI 1.29 to 2.07).Ondansetron and granisetron appear to be equivalent drugs for the prevention of acute and delayed emesis following the use of highly emetogenic chemotherapy.According to one single trial the combination of palonosetron and dexamethasone was superior to granisetron and dexamethasone in controlling delayed emesis. However, more evidence is needed before palonosetron could become the candidate 5-HT3 RA for the control of delayed emesis induced by highly emetogenic chemotherapy.
- Aprepitant Versus Dexamethasone for Preventing Chemotherapy-Induced Delayed Emesis in Patients With Breast Cancer: A Randomized Double-Blind Study. [JOURNAL ARTICLE]
- J Clin Oncol 2013 Dec 9.
A combination of aprepitant, a 5-HT3 receptor antagonist, and dexamethasone is recommended for the prophylaxis of acute or delayed emesis induced by chemotherapy containing anthracyclines plus cyclophosphamide in patients with breast cancer. The aim of this study was to verify whether dexamethasone is superior to aprepitant in preventing delayed emesis in patients receiving the same prophylaxis for acute emesis.A randomized double-blind study comparing aprepitant versus dexamethasone was completed in chemotherapy-naive patients with breast cancer treated with anthracyclines plus cyclophosphamide. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg, dexamethasone 8 mg, and oral aprepitant 125 mg. On days 2 and 3, patients randomly received oral dexamethasone 4 mg twice per day or aprepitant 80 mg once per day. Primary end point was rate of complete response (ie, no vomiting or rescue treatment) from days 2 to 5 after chemotherapy.Of 580 enrolled patients, 551 were evaluable: 273 received dexamethasone, and 278 received aprepitant. Day 1 complete response rates were similar: 87.6% for dexamethasone and 84.9% for aprepitant (P < .39). From days 2 to 5, complete response rates were the same with both antiemetic prophylaxes (79.5%; P < 1.00), as were results of secondary end points (ie, complete protection, total control, no vomiting, no nausea, score of Functional Living Index-Emesis; P < .24). Incidences of insomnia (2.9% v 0.4%; P < .02) and heartburn (8.1% v 3.6%; P < .03) were significantly greater with dexamethasone on days 2 to 5.In patients with breast cancer treated with anthracycline plus cyclophosphamide chemotherapy and receiving the same antiemetic prophylaxis for acute emesis, dexamethasone was not superior to aprepitant but instead had similar efficacy and toxicity in preventing delayed emesis.
- Palonosetron and dexamethasone for the prevention of nausea and vomiting in patients receiving allogeneic hematopoietic stem cell transplantation. [JOURNAL ARTICLE]
- Support Care Cancer 2013 Dec 7.
The primary aim of this study was to evaluate the efficacy of palonosetron combined with dexamethasone in the prevention of vomiting, and especially nausea, in patients receiving allogeneic stem cell transplantation.Palonosetron 0.25 mg was given to 27 patients receiving allogeneic transplantation on the first day of conditioning, and then every other day during the entire conditioning period. Dexamethasone was given daily also during conditioning. Vomiting and nausea were recorded daily according to CTCAE version 4.0 from the start of conditioning to Day 7 after transplantation. In addition, MASCC antiemetic tool (MAT) was also used in parallel to evaluate the intensity of nausea.The treatment was well tolerated; 25.9 and 40.7 % of the patients had grade 2/3 vomiting and nausea respectively during conditioning. The incidences of grade 2/3 vomiting and nausea were even higher in the first week after transplantation (40.7 and 51.8 %, respectively). The score of MAT correlated well with the grade of CTCAE. However, the difference in the mean intensity of nausea between period of conditioning and the first week after HSCT was significant only by using MAT (0.96 ± 1.829 vs. 3.81 ± 3.386, p = 0.001) but not CTCAE (1.26 ± 0.903 vs. 1.63 ± 0.967, p = 0.152).Palonosetron combined with dexamethasone is effective in preventing vomiting during conditioning. However, more effort should be made to alleviate nausea during conditioning and both nausea and vomiting in the first week after transplantation. Furthermore, MAT has a higher discriminant power than CTCAE in assessing the intensity of nausea in patients receiving allogeneic transplantation.
- Comparison of palonosetron with palonosetron-dexamethasone combination for prevention of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy. [JOURNAL ARTICLE]
- Minerva Anestesiol 2013 Nov 26.
Aim: This randomized double-blind study was designed to compare palonosetron with palonosetron-dexamethasone combination for prevention of post operative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy. Methods: Eighty four adult ASA 1-2 patients were randomly allocated into two groups. Group P patients received 0.075 mg palonosetron and group PD patients received 0.075 mg palonosetron and 8 mg dexamethasone intravenously before induction of anesthesia. Anesthesia was induced with propofol and fentanyl and maintained with N2O-isoflurane in oxygen. All patients received port-site infiltration with bupivacaine and intravenous diclofenac for postoperative analgesia. Metoclopramide was used as rescue antiemetic. Patients were observed for the incidence of PONV and requirement of rescue antiemetic for 48 h after surgery. Results: The complete response rate (no vomiting) was significantly higher in group DP as compared to group P between 0-24 h (P=0.004). 18 (42.9%) patients reported nausea and 14 (33.3%) patients had vomiting in group P while 6 (14.4%) patients had nausea and 5 (11.9%) patients complained of vomiting in group DP during 0-24 h. Two patients in group P reported nausea while none in group PD during 24-48 h. No patient had vomiting in either of the groups between 24-48 h. The requirement of rescue antiemetic was also less in group DP as compared to group P. Patients in group DP required less postoperative analgesia and were more satisfied with PONV treatment than group P patients. Conclusion: The palonosetron-dexamethasone combination was more effective as compared to only palonosetron for reducing PONV after laparoscopic cholecystectomy.
- Effectiveness of palonosetron for preventing delayed chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy in patients with gastrointestinal cancer. [JOURNAL ARTICLE]
- Support Care Cancer 2013 Nov 16.
Patients with gastrointestinal cancer who were receiving moderately emetogenic chemotherapy (MEC) were switched from granisetron, a first-generation 5-hydroxytryptamine-3 receptor antagonist, to palonosetron at our hospital. In the present study, we compared effectiveness before and after switching antiemetic treatment.Among patients who were receiving MEC for gastrointestinal cancer, we prospectively observed 46 patients given granisetron and 46 given palonosetron. To allow adverse reactions to be graded in accordance with the Common Terminology Criteria for Adverse Events, version 4.0, a questionnaire designed at our hospital was used to compare the occurrence of delayed nausea and vomiting between patients who received granisetron (GRA group) and those who received palonosetron (PAL group).The incidence of delayed nausea was significantly lower in the PAL group (8.7 %, 4/46; p < 0.01) than in the GRA group (37 %, 17/46). Delayed vomiting developed in five patients (10.9 %) in the GRA group, but did not occur in the PAL group. On the basis of the results of multivariate analysis, young age, female gender, and the use of granisetron were significant risk factors for delayed nausea.Our survey showed that palonosetron effectively controls delayed nausea caused by MEC for gastrointestinal cancer.
- Assessing physico-chemical compatibility of concomitantly diluted antiemetics including palonosetron-HCl and fosaprepitant dimeglumine. [JOURNAL ARTICLE]
- Cancer Chemother Pharmacol 2013 Nov 13.
- Molecular mechanisms of 5-HT3 and NK1 receptor antagonists in prevention of emesis. [JOURNAL ARTICLE]
- Eur J Pharmacol 2013 Oct 31.
Nausea and vomiting are major side effects of chemotherapy and one key reason for non-compliance with cancer treatment. The introduction of 5-HT3 receptor antagonists in the 1990s was a major advance in the prevention of acute emesis, and highlighted the critical role of serotonin in the emetic response. The next major advance in the treatment of chemotherapy induced nausea and vomiting (CINV) occurred in 2003 with the introduction of aprepitant, a tachykinin 1 (NK1) receptor antagonist. Aprepitant not only reduced acute emesis but also helped in the reduction of delayed emesis. Also in 2003, palonosetron, a second generation 5-HT3 receptor antagonist became available. Unlike the first generation 5-HT3 receptor antagonists, palonosetron demonstrated efficacy in preventing both acute and delayed emesis. This review focuses on the mechanism of action of 5-HT3 and NK1 receptor antagonists in acute and delayed CINV prevention. We discuss first, the medicinal chemistry that led to the discovery of these antagonists to underline their common structural features. Second, we discuss their performance in the clinic and what it tells us about the emetic response. Finally, we present recent mechanistic studies that help provide a rationale for efficacy differences between palonosetron and other 5-HT3 receptor antagonists in the clinic. In vitro and in vivo experiments have shown that palonosetron can inhibit substance P-mediated responses, presumably through its unique interactions with the 5-HT3 receptor. The crossroads of acute and delayed emesis seem to include interactions among the 5-HT3 and NK1 receptor signaling pathways and inhibitions of these interactions could lead to improved treatment of CINV.
- Efficacy of palonosetron for the prevention of postoperative nausea and vomiting: a randomized, double-blinded, placebo-controlled trial. [JOURNAL ARTICLE]
- Br J Anaesth 2013 Oct 22.
/st>The aim of this study was to evaluate the efficacy of palonosetron, the latest 5-HT3 receptor antagonist, for the prevention of postoperative nausea and vomiting (PONV) during the first 72 h after operation./st>In this randomized, double-blinded, placebo-controlled study, 204 healthy inpatients who were undergoing elective surgery with general anaesthesia were enrolled. Patients were divided into two groups: the palonosetron group (palonosetron 0.075 mg i.v.; n=102) and the placebo group (normal saline i.v.; n=102). The treatments were given after the induction of anaesthesia. The incidence of nausea, vomiting, severity of nausea, and the use of rescue anti-emetics during the first 72 h after surgery were evaluated./st>The incidence of PONV was lower in the palonosetron group compared with the placebo group during the 0-24 h (33% vs 47%) and 0-72 h period (33% vs 52%) (P<0.05), but not during the 24-72 h postoperative period (6% vs 11%). The incidence of nausea was also significantly lower in the palonosetron group than in the placebo group during the 0-24 and 0-72 h period (P<0.05), but not during the 24-72 h postoperative period. However, there were no significant differences in the incidence of vomiting, and the use of rescue anti-emetics between the groups./st>Palonosetron 0.075 mg i.v. effectively reduced the incidence of PONV during the first 72 h after operation, with most of the reduction occurring in the first 24 h.
- Pooled analysis of phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV). [JOURNAL ARTICLE]
- Support Care Cancer 2013 Oct 19.
Preventing chemotherapy-induced nausea and vomiting (CINV) is integral to treatment success in patients with cancer. This analysis was undertaken to assess the relative efficacy and safety of palonosetron versus older 5HT3 RAs in preventing CINV associated with moderately or highly emetogenic chemotherapy.Patient-level data from four randomized, double-blind, phase III trials comparing palonosetron 0.25 or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg were analyzed. Endpoints included complete response (CR: no emesis and no rescue antiemetics) in the acute (0-24 h), delayed (>24-120 h), and overall (0-120 h) postchemotherapy periods (primary), complete control (CC: no emesis, no rescue antiemetics, and no more than mild nausea), number of emetic episodes, and nausea severity.CR rates were significantly higher for palonosetron (n = 1,787) versus older 5HT3 RAs (n = 1,175) in the delayed (57 vs 45 %, P < 0.0001) and overall periods (51 vs 40 %, P < 0.0001); odds ratios (95 % CI) in the acute, delayed, and overall periods were 1.15 (0.98-1.34), 1.62 (1.40-1.88), and 1.56 (1.34-1.81), respectively. Significant differences in CC rates and nausea severity were observed for the delayed and overall periods and in emetic episodes for all three periods. The incidence of treatment-related adverse events was similar with palonosetron (0.25 mg, 20.0 %; 0.75 mg, 26.5 %) and older 5HT3 RAs (27.5 %).Palonosetron is more effective than older 5HT3 RAs for controlling CINV in the delayed and overall postchemotherapy periods.
- Effect of palonosetron on the QTc interval in patients undergoing sevoflurane anaesthesia. [JOURNAL ARTICLE]
- Br J Anaesth 2013 Oct 14.
/st>Palonosetron is a recently introduced 5-HT3 receptor antagonist for postoperative nausea and vomiting. Detailed standardized evaluation of corrected QT (QTc) interval change by palonosetron under sevoflurane anaesthesia is lacking. We evaluated QTc intervals in patients who are undergoing surgery with sevoflurane anaesthesia and receive palonosetron./st>Our study included 100 patients who were undergoing elective surgery under sevoflurane anaesthesia. The patients were randomly assigned to two groups: those who received an i.v. injection of palonosetron 0.075 mg immediately before induction of anaesthesia (pre-surgery group, n=50) and those who received it after surgery in the recovery room (post-surgery group, n=50). QTc intervals were measured before operation, intraoperatively (baseline, immediately after tracheal intubation, and at 2, 10, 15, 30, 60, and 90 min after administration of palonosetron or placebo), and after operation (before and at 3, and 10 min after administration of palonosetron or placebo). QTc intervals were calculated using Fridericia's, Bazett's, or Hodges formulas./st>The perioperative QTc intervals were significantly increased from the baseline values, but were not affected by the pre- or post-surgical timing of palonosetron administration./st>There was no significant difference in the QTc intervals during the perioperative period, whether 0.075 mg of palonosetron is administered before or after sevoflurane anaesthesia. Palonosetron may be safe in terms of QTc intervals during sevoflurane anaesthesia.Clinical trial registrationClinicalTrials.gov: NCT01650961.