昂丹司琼、格拉司琼和帕洛诺司琼预防食管癌术后化疗所致恶心、呕吐的效果观察

目的 比较昂丹司琼、格拉司琼和帕洛诺司琼预防食管癌术后化疗所致恶心、呕吐的临床效果及安全性.方法 将60例食管癌术后患者随机分为昂丹司琼组、格拉司琼组和帕洛诺司琼组,各20例,均行顺铂等药物化疗,并分别给予昂丹司琼、格拉司琼和帕洛诺司琼预防恶心、呕吐反应;观察3组患者恶心、呕吐的控制效果及不良反应.结果 昂丹司琼组、格拉司琼组和帕洛诺司琼组患者恶心、呕吐控制急性期有效率分别为55％、60％、75％,帕洛诺司琼组与其他两组比较,差异有统计学意义（P＜0.05）;延迟期有效率分别为40％、45％、75％,帕洛诺司琼组与其他两组比较,差异有统计学意义（P＜0.05）.结论 帕洛诺司琼预防化疗所致恶心、呕吐效果较昂丹司琼、格拉司琼更优,安全性相似,且临床应用方便.     

帕洛诺司琼与昂丹司琼在头颈癌化疗中止吐效果的比较

目的观察帕洛诺司琼和昂丹司琼防治头颈癌化疗引起的恶心呕吐的疗效和不良反应。方法 46例头颈癌患者被随机分为帕洛诺司琼组和昂丹司琼组,分别在化疗前静脉推注帕洛诺司琼0.25 mg或昂丹司琼8 mg。观察两组在化疗急性期、延迟期和全期防治恶心呕吐的效果和不良反应。结果两组止吐药物在急性期均有良好的止吐效果,帕洛尼司琼组有效率为95.2%,昂丹司琼组有效率为88%。两组相比无统计学差异(P>0.05)。而延迟治疗期和全期帕洛尼司琼组有效率分别为85.7%、80.9%,优于昂丹司琼组的64%和56%(P<0.05)。两组止吐药物在急性期和延迟期均有良好的抑制恶心的效果,帕洛尼司琼组有效率分别为90.4%、80.9%,昂丹司琼组有效率分别为84%、72%。两组相比无统计学差异(P>0.05)。而全期帕洛尼司琼组有效率分别为71.4%,优于昂丹司琼组的56%(P<0.05)。两组不良反应差异无统计学意义。结论帕洛诺司琼对防治头颈癌化疗引起的急性期和延迟期发生的恶心呕吐均有较好疗效。     

盐酸帕洛诺司琼与格拉司琼预防化疗所致呕吐的效果比较

目的:对比分析盐酸帕洛诺司琼与格拉司琼预防化疗所致呕吐的效果。方法:选取2009年~2013年8月在某院进行化疗的74例恶性肿瘤患者作为研究对象。将患者随机分为盐酸帕洛诺司琼组(静注0.25mg)和格拉司琼组(静注3mg),每组37例。对比两组患者呕吐的控制效果和不良反应的发生状况。结果:盐酸帕洛诺司琼组患者的完全缓解和部分缓解比例均高于格拉司琼组,而无效比例低于格拉司琼组,差异均有统计学意义(P0.05)。盐酸帕洛诺司琼组患者共发生不良反应4例,发生率为10.81%,格拉司琼组共发生不良反应6例,发生率为16.22%。两组间的差异无统计学意义(P0.05)。结论:与格拉司琼相比,盐酸帕洛诺司琼预防化疗所致呕吐的效果更好,值得在临床实践中应用。     

盐酸帕洛诺司琼对比格拉司琼在老年急性髓系白血病化疗相关恶心和呕吐的临床研究

目的比较盐酸帕洛诺司琼与格拉司琼在老年急性髓系白血病(AML)化疗相关恶心呕吐(CINV)反应治疗效果。方法将符合纳入标准的老年AML患者24例,按随机数字表法分为试验组和对照组,每组各12例,试验组采用盐酸帕洛诺司琼注射液预防呕吐,对照组使用格拉司琼治疗,观察2组患者化疗期间及化疗后第1～5天的恶心、呕吐、食欲以及全身情况。结果帕洛诺司琼对比格拉司琼预防化疗过程中及化疗后急性CINV控制有效率分别为92%和83%,在治疗后48 h迟发性CINV的有效率分别是92%和83%,2组间比较差异有统计学意义(P<0.05);盐酸帕洛诺司琼在迟发性呕吐分层缓解率高于格拉司琼,2种药物均有轻微疲乏、便秘、头晕、头痛等不良反应。结论在老年AML化疗中,帕洛诺司琼对于预防CINV的疗效优于格拉司琼,不良反应发生率低、程度轻。     

盐酸帕洛诺司琼与托烷司琼预防化疗所致恶心呕吐疗效的临床观察

目的:比较盐酸帕洛诺司琼与托烷司琼预防化疗所致恶心呕吐的疗效和不良反应。方法:回顾性分析112例恶性肿瘤患者分别应用托烷司琼和盐酸帕洛诺司琼,两组均为56例患者,分别使用烷司琼4mg+地塞米松5mg或盐酸帕洛诺司琼0.25mg+地塞米松5mg于化疗前半小时使用。对比两组患者急性和延迟性呕吐的完全缓解率、进食量和不良反应。结果:托烷司琼组和盐酸帕洛诺司琼组急性呕吐的完全缓解率分别为73.2%(41/56)和78.6%(44/56),P0.05;延迟性呕吐的完全缓解率分别为48.2%(27/56)和71.4%(40/56),差异有统计学意义(P0.05);托烷司琼和盐酸帕洛诺司琼治疗后,患者因食欲下降致进食量明显减少的发生率分别为51.8%(29/56)和19.6%(11/56),差异有统计学意义(P0.05);托烷司琼和盐酸帕洛诺司琼治疗后,两组患者不良反应的发生率均较低,程度也较轻。结论:盐酸帕洛诺司琼对延迟性呕吐的缓解效果更优,且患者的不良反应可以耐受;盐酸帕洛诺司琼良好的呕吐控制效果保证了化疗期间患者有足够的能量摄入。     

帕洛诺司琼联合地塞米松预防含多天顺铂方案化疗引起恶心、呕吐的临床观察

目的观察和比较5-HT3受体拮抗剂帕洛诺司琼与托烷司琼联合地塞米松预防含多天顺铂方案化疗引起恶心、呕吐的疗效及安全性。方法将连续使用2周期含多天顺铂方案化疗的住院恶性肿瘤患者,按随机、交叉自身对照的方法分为AB、BA组。AB组病例第1周期的第1、3天化疗前静脉滴注帕洛诺司琼0.25 mg,并于每天化疗前静脉滴注地塞米松10 mg。BA组病例第1周期的第1~3天化疗前均分别静脉滴注托烷司琼5 mg和地塞米松10 mg。第2周期的止吐方案为两组病例第1周期的止吐方案交叉使用。观察化疗开始后7 d内患者恶心、呕吐的控制情况及不良反应发生率。结果共入组49例病例,47例可评价疗效:AB组23例,BA组24例;两组患者在年龄、性别、有无化疗史及病种等方面无显著性差异(P>0.05)。帕洛诺司琼组在延迟期和全期的化疗相关性恶心呕吐(CINV)的完全控制率显著高于托烷司琼组,分别为57.4%(27/47)和34.0%(16/47),P=0.023;55.3%(26/47)和29.8%(14/47),P=0.012。但在急性CINV方面,两组患者的完全控制率无显著性差异,分别为63.8%(30/47)和53.2%(22/47),P>0.05。两种止吐药物的不良反应多表现为便秘、头痛、疲劳、呃逆等,发生率较低,程度较轻,差异无统计学意义(P>0.05)。结论帕洛诺司琼对含多天顺铂方案化疗引起的迟发性CINV的完全控制率优于托烷司琼。多剂量帕洛诺司琼联合全程使用地塞米松的不良反应轻微。     

帕洛诺司琼防治乳腺癌化疗相关性恶心呕吐的临床对照研究

目的 观察帕洛诺司琼防治乳腺癌化疗相关性恶心呕吐的疗效及安全性.方法 选择2010年1月-2013年6月沈阳军区总医院收治的乳腺癌77例,其中帕洛诺司琼组（A组）38例和托烷司琼组（B组）39例.两组患者均采用含表柔比星方案化疗,分别观察两组化疗后0~5 d内出现恶心、呕吐及食欲不振等消化道反应和便秘、头晕等不良反应.结果化疗后0~24 h两组恶心、呕吐及食欲不振控制率差异均无统计学意义（P＞0.05）,化疗后2~5 d A组对恶心、呕吐控制率明显优于B组（P＜0.05）,食欲不振控制率无差异（P＞0.05）.两组不良反应较轻,无明显差异（P＞0.05）.结论 在乳腺癌化疗中,帕洛诺司琼防治表柔比星引起迟发性恶心呕吐疗效显著,安全性高.     

盐酸帕洛诺司琼预防高中度致吐性化疗引起恶心呕吐的临床观察

目的观察盐酸帕洛诺司琼预防高、中度致吐性化疗方案引起的恶心呕吐的疗效和安全性。方法对应用高、中度致吐性化疗方案的患者,化疗前30min静脉注射盐酸帕洛诺司琼0.25mg,观察患者化疗后出现急性呕吐、延迟性呕吐和恶心的控制情况及相关不良反应的发生情况,对影响盐酸帕洛诺司琼疗效进行多因素分析。结果 1379例患者中接受高度致吐性化疗方案化疗者555例(高致吐性组)、中度致吐性化疗方案化疗者824例(中致吐性组)。在高致吐性组盐酸帕洛诺司琼对急性呕吐、延迟性呕吐以及0～5d呕吐的控制率分别为68.1%、64.7%及60.9%,Ⅰ、Ⅱ、Ⅲ度恶心的发生率分别为40.1%、20.2%及9.5%;中致吐性组盐酸帕洛诺司琼对急性呕吐、延迟性呕吐以及0～5d呕吐的控制率分别为85.2%、72.1%及68.2%,Ⅰ、Ⅱ、Ⅲ度恶心的发生率分别为29.9%、16.5%及5.6%。多因素分析结果:性别、年龄、化疗药物、电解质紊乱、既往化疗呕吐史和合并使用其他止吐药物等是影响盐酸帕洛诺司琼疗效的主要因素。不良反应:腹胀11例(0.8%)、便秘36例(2.6%)和头痛68例(4.9%)。结论盐酸帕洛诺司琼对高、中度致吐性化疗方案化疗引起的恶心呕吐有良好的治疗效果,安全性好。     

帕洛诺司琼预防腹腔镜低位保肛直肠癌根治结合缓释型氟尿嘧啶植入术后恶心呕吐的作用及安全性

目的观察帕洛诺司琼对腹腔镜低位保肛直肠癌根治结合缓释型氟尿嘧啶植入术后恶心呕吐的有效性与安全性。方法进展期直肠癌患者200例,随机分为帕洛诺司琼组和托烷司琼组,每组100例。两组均接受腹腔镜低位保肛直肠癌根治术结合缓释型氟尿嘧啶植入综合治疗,帕洛诺司琼组和托烷司琼组在综合治疗前30 min分别予帕洛诺司琼0.25 mg iv和托烷司琼5 mg iv。记录两组患者术后3 d内的恶心呕吐发生情况,观察不良反应的发生情况。结果术后第1日,帕洛诺司琼组和托烷司琼组恶心的发生率分别为31%和46%,术后3 d内分别为31%和48%,两组相比有显著差异(P <0.05)。两组术后第2日的恶心发生率和各时间点的呕吐发生率均无显著差异(P> 0.05)。两组头痛、便秘、腹胀的发生率无显著差异(P> 0.05),帕洛诺司琼组眩晕的发生率低于托烷司琼组(7%vs. 17%, P <0.05)。结论帕洛诺司琼预防腹腔镜低位保肛直肠癌根治术结合缓释型氟尿嘧啶植入综合治疗后所致恶心的效果优于托烷司琼,且安全。     

帕洛诺司琼联合地塞米松预防甲状腺切除术后恶心、呕吐

目的观察帕洛诺司琼联合地塞米松对甲状腺切除术患者术后恶心呕吐的预防作用。方法 120例行甲状腺切除术患者随机分为联合组、帕洛诺司琼组、对照组,预计手术结束前30 min,对照组静脉注射生理盐水2 mL,帕洛诺司琼组静脉注射帕洛诺司琼0.25 mg,联合组静脉注射帕洛诺司琼0.25 mg和地塞米松10 mg。观察三组术后24 h发生恶心呕吐情况并作比较。结果联合组恶心呕吐的发生率明显优于对照组(P<0.05)。结论帕洛诺司琼联合地塞米松可降低甲状腺切除患者术后恶心呕吐发生率。     

Palonosetron

Palonosetron is a potent and highly selective serotonin 5-HT(3) receptor antagonist that has been evaluated for the prevention of chemotherapy-induced nausea and vomiting. black triangle Intravenously administered palonosetron has a linear pharmacokinetic profile, with a long terminal elimination half-life ( approximate, equals 40 hours) and moderate (62%) plasma protein binding. In two randomised, double-blind trials in 1132 cancer patients receiving moderately emetogenic chemotherapy, intravenous palonosetron 0.25 mg was more effective than intravenous ondansetron 32 mg in producing a complete response (no emesis, no use of rescue medication) during acute (0-24 hours) or delayed (24-120 hours) phases, and similar to intravenous dolasetron 100 mg in acute, but more effective in delayed phase. Palonosetron 0.75 mg was similar to ondansetron (acute and delayed phase) or dolasetron (acute phase), but more effective than dolasetron in delayed phase. In patients receiving highly emetogenic chemotherapy (n = 667), the complete response rates during acute and delayed phases with intravenous palonosetron (0.25 or 0.75 mg) were similar to those seen in intravenous ondansetron 32 mg recipients in a randomised, double-blind trial. Intravenous palonosetron was generally well tolerated in clinical trials, with few adverse events being treatment related. Palonosetron had no significant effect on the corrected QT interval or laboratory parameters.     

The current status of the use of palonosetron

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in the quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient characteristics (female gender, younger age, low alcohol consumption, history of motion sickness) are the major risk factors for CINV. Palonosetron, a second-generation 5-hydroxytryptamine 3 (5-HT₃) receptor antagonist, has antiemetic activity at both central and gastrointestinal sites. In comparison to the first-generation 5-HT₃ receptor antagonists, it has a higher potency, a significantly longer half-life, and a different molecular interaction with 5-HT₃ receptors. Palonosetron has been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. Compared to the first-generation 5-HT₃ receptor antagonists, palonosetron in combination with dexamethasone has demonstrated better control of delayed CINV in patients receiving highly emetogenic chemotherapy and had a similar safety profile. Due to its efficacy in controlling both acute and delayed CINV, palonosetron may be very effective in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.     

帕洛诺司琼联合小剂量地塞米松治疗顺铂致恶心呕吐的临床观察

目的 探讨帕洛诺司琼联合小剂量的地塞米松在防治顺铂引起的恶心、呕吐中的疗效和安全性.方法 采用随机信封方法将60例采用顺铂化疗的肿瘤患者分为对照组(29例)和联合组(31例).对照组用药为盐酸帕洛诺司琼注射液0.25 mg,第1、3天静脉注射;联合组在对照组基础上联合地塞米松5 mg/d,第1～3天静脉推注.对化疗后恶心呕吐疗效进行评价,并观察地塞米松所致的不良反应.结果 化疗期间,对照组急性呕吐有效22例(75.9％),无效7例(24.1％),延迟性呕吐有效20例(69.0％),无效9例(31.0％).联合组急性呕吐有效24例(77.4％),无效7例(22.6％);延迟性呕吐有效26例(83.9％),无效5例(16.1％).联合组对于延迟性呕吐疗效优于对照组(P＜0.05).地塞米松应用期间,发生血压和血糖升高2例,兴奋1例,失眠1例,皮疹1例,但均可控制.结论 盐酸帕洛诺司琼注射液联合小剂量的地塞米松能够预防化疗引起的延迟性恶心、呕吐,疗效和安全性较好.     

盐酸氯丙嗪联合帕洛诺司琼预防化疗药物致恶心呕吐的临床观察

目的探讨盐酸氯丙嗪联合帕洛诺司琼预防化疗药物致恶心呕吐的临床疗效.方法 2014年1月—2014年7月在襄阳市中心医院行高致吐性化疗药物的住院患者126例,随机分为对照组和治疗组,每组63例.对照组患者在化疗第1天,开始化疗前30 min静脉滴注盐酸帕洛诺司琼注射液,0.25 mg/次,1次/d,注射时间30 s以上.治疗组在对照组基础上肌肉注射盐酸氯丙嗪注射液25 mg/次.3周为1个化疗周期,两组在1个化疗周期后观察恶心、呕吐的控制率.结果对照组和治疗组急性呕吐控制率分别为76.19%、84.13%,延迟性呕吐控制率分别为50.79%、63.49%,治疗组急性、延迟性呕吐控制率均显著高于对照组,两组比较差异具有统计学意义(P<0.05).对照组和治疗组急性恶心控制率分别为58.73%、77.78%,延迟性恶心控制率分别为 49.21%、65.08%,两组比较差异具有统计学意义(P<0.05).对照组和治疗组急性食欲减退控制率分别为87.30%、90.48%,延迟性食欲减退控制率分别为84.12%、87.30%,两组比较差异无统计学意义.结论 盐酸氯丙嗪联合帕洛诺司琼预防化疗药物致恶心呕吐具有较好的临床疗效,且不会增加不良反应,值得临床推广应用.     

Cutaneous analgesia after subcutaneous injection of memantine and amantadine and their systemic toxicity in rats

Netupitant is a potent and selective NK(1) receptor antagonist under development in combination with a fixed dose of palonosetron for the prevention of chemotherapy induced nausea and vomiting. Palonosetron is a 5-HT(3) receptor antagonist approved for both the prevention of acute and delayed chemotherapy induced nausea and vomiting after moderately emetogenic chemotherapy. Accumulating evidence suggests that substance P (SP), a ligand acting largely on tachykinin (NK(1)) receptors, is the dominant mediator of delayed emesis. Interestingly, palonosetron does not bind to the NK(1) receptor so that the mechanism behind palonosetron's unique efficacy against delayed emesis is not clear. Palonosetron exhibits a distinct ability among 5-HT(3) receptor antagonists to inhibit crosstalk between NK(1) and 5-HT(3) receptor signaling pathways. The objective of the current work was to determine if palonosetron's ability to inhibit receptor signaling crosstalk would influence netupitant's inhibition of the SP-mediated response when the two drugs are dosed together. We first studied the inhibition of SP-induced Ca(2+) mobilization in NG108-15 cells by palonosetron, ondansetron and granisetron. Unexpectedly, in the absence of serotonin, palonosetron inhibited the SP-mediated dose response 15-fold; ondansetron and granisetron had no effect. Netupitant also dose-dependently inhibited the SP response as expected from an NK1 receptor antagonist. Importantly, when both palonosetron and netupitant were present, they exhibited an enhanced inhibition of the SP response compared to either of the two antagonists alone. The results further confirm palonosetron's unique pharmacology among 5-HT(3) receptor antagonists and suggest that it can enhance the prevention of delayed emesis provided by NK(1) receptor antagonists.     

Antiemetic control: toward a new standard of care for emetogenic chemotherapy

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. 5-hydroxytryptamine-3 (5-HT₃) receptor antagonists plus dexamethasone have significantly improved the control of acute CINV, but delayed CINV remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have been approved for the prevention of both acute and delayed CINV. Palonosetron is a second-generation 5-HT₃ receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT₃ receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 (NK-1) receptor antagonists. Casopitant is another NK-1 receptor antagonist that is under review by the FDA after recent completion of Phase III clinical trials. The introduction of these new agents has generated revised antiemetic guidelines for the prevention of CINV. Future studies may consider the use of palonosetron, aprepitant and casopitant with other antiemetic agents (olanzapine, gabapentin, cannabinoids) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.     

Emerging drugs for chemotherapy-induced emesis

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient risk factors (female gender, younger age, no alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have recently been approved for the prevention of both acute and delayed CINV. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 receptor (NK-1) antagonists. There are a number of 5-HT3 receptor antagonists and NK-1 receptor antagonists currently in Phase II and III clinical trials. Revised antiemetic guidelines for the prevention of CINV are reviewed. Future studies may consider the use of palonosetron and aprepitant with current and other new agents (olanzapine, gabapentin) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.     

帕诺洛司琼与托烷司琼分别联合地塞米松预防含顺铂化疗所致恶心呕吐的临床对照研究

目的:观察和评价国产帕洛诺司琼联合地塞米松预防含高致吐性顺铂化疗引起的恶心、呕吐的有效性和安全性。方法:采用随机对照的试验方法,对使用含高致吐性顺铂（≥50mg/m2）化疗方案的患者,于化疗前半小时缓慢静脉推注帕洛诺司琼0.25mg (观察组)或静滴托烷司琼2mg (对照组),两组均于第1、2、3天化疗前分别静脉滴入地塞米松16mg、8mg、8mg,观察患者化疗引起的急性期（0-24h）、延迟期（24-120h及全期（0-120h）的呕吐的完全缓解率及无呕吐发作百分比,必要时给予解救性止吐治疗(托烷司琼或甲氧氯普胺)。结果:共入组72例患者,观察组35例,对照组37例,观察组对化疗引起的急性期、延迟期完全缓解率(CRR)与对照组相比无显著性差异(82.9%vs75.7%、65.7% vs43.2%,P＞0.05),但前者对化疗引起的全期CRR明显高于对照组(65.7% vs40.5%,P＜0.05）);观察组化疗后急性期无呕吐发作率与对照组相比无显著性差异（91.4%vs 83.8%, P＞0.05）,但在延迟期及全期则具有显著性差异（77.1% vs48.6%、74.3%vs43.2%, P＜0.05）。两组不良反应主要为头痛、便秘、眩晕、腹部不适等,均症状轻微,患者耐受性好。 结论:国产帕洛诺司琼联合地塞米松能有效地预防高致吐性化疗所致急性期、延迟期呕吐反应,对于延迟期呕吐反应其疗效优于托烷司琼,且安全性好。