盐酸帕洛诺司琼注射液课件

1、止 若盐酸帕洛诺司琼注射液江苏正大天晴药业股份有限公司九月 221止若基本信息通用名：盐酸帕洛诺司琼注射液商品名：止若 规格： 5ml:0.25mg包装：安瓿装，1支/盒药理分类：抗肿瘤辅助药化疗止吐药属5-HT3受体拮抗剂适应症：1、预防高度致吐化疗引起的急性恶心、呕吐；2、预防中度致吐化疗引起的恶心、呕吐。用法用量：化疗前约30分钟，单剂量静脉注射帕洛诺司琼0.25mg，注射时间为30秒以上。九月 222肿瘤治疗相关呕吐对病人生活质量影响轻微 ：不适感严重 ：脱水、电解质紊乱、营养不良、 胃肠道粘膜撕裂出血治疗依从性降低治疗贻误中止有效治疗CINV Compromises Quality

2、of Daily Life Group 1: n=166; Group 2: n=30; Group 3: n=157; Group 4: n=332 aGroup 1 vs. Group 4, p=0.007; bGroup 1 vs. Group 4, p=0.0001; cGroup 3 vs. Group 4, p=0.0002; dGroup 3 vs. Group 4, p=0.003; eGroup 1 vs. Group 4, p=0.0001; fGroup 2 vs. Group 4, p=0.0005; gGroup 3 vs. Group 4, p=0.002Adapt

3、ed from Osoba D et al Support Care Cancer 1997;5:307313.Mean changes in functional domain scores of health-related quality of life after eight days of chemotherapy Mean change in scoreQuality of Life DiminishedQuality of Life ImprovedGroup 1 (no nausea or vomiting)Group 2 (vomiting, no nausea)Group

4、3 (nausea, no vomiting)Group 4 (nausea and vomiting)201510505101.9b0.61.1c0.5d8.8e0.6f1.17.4g14.23.8a5.78.70.8PhysicalEmotionalCognitiveSocialGlobalFunctional domainNeed for Improved Control of CINV198319961Being sick (vomiting)Feeling sick (nausea)2Feeling sick (nausea)Loss of h

5、air3Loss of hairBeing sick (vomiting)4Thought of coming for treatmentConstantly tired5Duration of treatment at the clinicNeed for an injection6Need to get a needleConstipation7Shortness of breat Thought of coming for treatment8Constantly tiredAffects family or partner9Difficulty sleepingFeeling low,

6、 miserable (depression)10Affects family or partnerFeeling anxious or tenseMost distressing adverse effects of chemotherapy before and during 5-HT3 receptor antagonist era Adapted from de Boer-Dennert M et al Br J Cancer 1997;76(8):10551061; Coates A et al Eur J Cancer Clin Oncol 1983;19:203208.关注三种药

7、物九月 227这是卡铂、环磷酰胺、顺铂的呕吐强度图。由于药物随着时间推移仍会出现呕吐，这里需要特别注意，这三种药物易引起延迟性呕吐。5-HT3RA的作用机制迷走神经化疗常用5-HT3R拮抗剂的结构与5HT相似的吲哚环 融合的三环结构Rojas C, Anesth Analg,2008;107:469 478.常用5-HT3R拮抗剂的特点消除半衰期与5-HT3R亲和力pKi（-Ki） 用法分类 恩丹西酮34h8.398mg，3次/日第一代多拉司琼7.3h7.610mg/日第一代托烷司琼8h/5mg/日第一代格拉司琼9h8.913mg/日第一代雷莫司琼6h/0.3mg/日第一代帕洛诺司琼40h10

8、.450.25mg第二代第一代5-HT3RA主要临床研究结果时间药物n致吐风险急性延迟性呕吐(%)恶心(%)呕吐(%)恶心(%)1996dolasetron 403中高42.2/1998Ondansetron 184高5843/Granisetron187高5135/2003dolasetron191中52.9/38.7322004ramosetron134高54574131.92006Ondansetron98中高/49.5/2006Ondansetron221高57/38.9/N Engl J Med 1995;332:1-5. J Clin Oncol 1996,14:2242-2249

9、. Support Care Cancer,2004,2:5863 Anti-Cancer Drugs 2006, 17:217224Annals of Oncology 2006,17:1441-1449, Cancer 2003;98:247382.*：呕吐有效率III期临床帕洛诺司琼vs 昂丹司琼用于中度致吐性化疗研究设计：III期随机，多中心，双盲，主动控制, 分层, 平行试验中度致吐性化疗n = 563第1天:Palonosetron 0.25 mg IVPalonosetron 0.75 mg IVOndansetron 32 mg IV没有预防给予皮质类固醇病人14天后进行评估G

10、ralla R et al. Ann Oncol. 2003;14:1570-1577.Palonosetron vs Ondansetron: CINV 完全控制率Palonosetron 0.25 mg (n=189)Palonosetron 0.75 mg (n=189)Ondansetron 32 mg (n=185)Time (hr)020406080100Acute: 0-24(Day 1)Delayed: 24-120(Days 2-5)Overall: 0-120(Days 1-5)Complete Response (% of Patients) *81.073.568.6*

11、74.164.655.1*69.358.750.3*97.5% CIs and 2-sided Fishers exact test (significance level = 0.025) indicate a difference between palonosetron and ondansetron.Complete response (CR): no emesis, no rescue medication.Gralla R et al. Ann Oncol. 2003;14:1570-1577. III期临床帕洛诺司琼VS多拉司琼Eisenberg P,Cancer，2003;98

12、:24732482.帕洛诺司琼（止若）预防肿瘤化疗性恶心呕吐的双盲双模拟、随机、阳性药平行对照的多中心临床试验双盲随机试验组=111帕洛诺司琼0.25mg对照组=112格拉司琼 3mg1次用药7天观察研究设计 盐酸帕洛诺司琼注射液/空白模拟剂 5ml空白模拟剂 3ml/盐酸格拉司琼注射液生理盐水 12ml20mlIv 30秒以上化疗前半小时第7天解救治疗解救治疗标准：呕吐发作2次/日解救治疗方法：格拉司琼3mg 地塞米松5mg呕吐控制情况九月 2220P=0.0282P=0.0140P=0. 1420急性呕吐CRR延迟性呕吐CCR0-7天呕吐控制情况呕吐控制时间呕吐为化疗后小时，而对照组为化疗

13、后0.5小时。两组化疗后呕吐控制时间(小时)中位值分别为168.00112.00(平均)和168.00 140.00(平均)，其差异具有显著性(P=0.0377)，提示试验组呕吐控制时间较长。九月 2221最早呕吐时间(h)平均呕吐控制时间(h)试验组3.0121.7864.87对照组0.5103.10 70.55两组病人用药后恶心程度的比较 数据集组别程度平均分P0123合计FAS受试组49352071110.860.930.0198对照组35333771121.140.94PPS受试组46342071070.890.930.0474对照组32313361021.130.93CINV治疗策略

14、的发展单药5-HT3RA双药治疗(+地塞米松)三药联合(+地塞米松+ NK1 RA)更多多天给药化疗方案的呕吐预防高中度致吐风险的化疗方案，5-HT3 RA 和地塞米松应在每天化疗药物应用前给予化疗期间和结束后2-3 天均可出现延迟性呕吐Palonosetron 可以用于多天化疗方案以代替其他需要每天使用的5-HT3 RA ，且重复使用可认为是安全的不良反应帕洛诺司琼昂丹司琼多拉司琼例数例数例数总例数（人）633410194静注剂量（mg）0.2532100头痛6093483216便秘29582126腹泻817242头昏819242疲劳314142腹痛112132失眠113132九月 2227预防化疗诱发恶心和呕吐研究中2%患者中出现的不良反应止若优势止若半衰期长，可“全程控制”化疗引起的恶心呕吐！ 止若显示出“全面控制”化疗引起的急性和延迟性恶心呕吐的作用。 国际多个指南权威推荐：帕洛诺司琼（止若）用于高度和中度致吐性化疗引起的恶心呕吐。九月 222