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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,2018年9月,1,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。,2018年9月,2,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
2、,CINV Compromises Quality 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
3、 vs. Group 4, p=0.002 Adapted 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 score,Quality of Life Diminished,Quality of Life Improved,Group 1 (no nausea or vomiting) Gro
4、up 2 (vomiting, no nausea) Group 3 (nausea, no vomiting) Group 4 (nausea and vomiting),20,15,10,5,0,5,10,1.9b,0.6,1.1c,8.4,2.6,0.6,0.5d,8.8e,0.6f,1.1,7.4g,14.2,3.8a,5.7,8.7,10,5.3,5.3,4.9,0.8,Physical,Emotional,Cognitive,Social,Global,Functional domain,Need for Improved Control of CINV,1983 1996 1 B
5、eing sick (vomiting) Feeling sick (nausea) 2 Feeling sick (nausea) Loss of hair 3 Loss of hair Being sick (vomiting) 4 Thought of coming for treatment Constantly tired 5 Duration of treatment at the clinic Need for an injection 6 Need to get a needle Constipation 7 Shortness of breat Thought of comi
6、ng for treatment 8 Constantly tired Affects family or partner 9 Difficulty sleeping Feeling low, miserable (depression) 10 Affects family or partner Feeling anxious or tense,Most distressing adverse effects of chemotherapy before and during 5-HT3 receptor antagonist era,Adapted from de Boer-Dennert
7、M et al Br J Cancer 1997;76(8):10551061; Coates A et al Eur J Cancer Clin Oncol 1983;19:203208.,CINV分类,急性呕吐 化疗后24h内发生 延迟性呕吐 化疗后24h or 更长时间 预期性呕吐 曾有CINV经历，化疗前、中、后发生 暴发性呕吐 预防处理后发生 难治性呕吐 CINV预防、解救治疗失败,关注三种药物,2018年9月,7,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,5-HT
8、3 RA的分类,第一代 Ondansetron（枢复宁）-1984年开发，1991年批准上市 Tropisetron-欧洲 Granisetron-1988年开发，1991 及1994年分别在英国及美国被批准上市 Dolasetron-1997年批准上市 Ramosetron-日本及东亚地区 第二代 Palonosetron-2003年,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,第一代5-HT3RA主要临床研究结果,N Engl J Med 1995;332:
9、1-5. J Clin Oncol 1996,14:2242-2249. Support Care Cancer,2004,2:5863 Anti-Cancer Drugs 2006, 17:217224 Annals of Oncology 2006,17:1441-1449, Cancer 2003;98:247382.,*：呕吐有效率,第二代5-HT3RA 帕洛诺司琼,化学名：2一1一氮杂双环(222)辛一3S一基一2，3，3aS，4，5，6一六氢一1 H一苯并de异喹啉一1一酮盐酸盐 分子式为C19H24N2OHCL 分子量332.87 属第二代高选择性5-HT3受体拮抗剂,III期临
10、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 IV Palonosetron 0.75 mg IV Ondansetron 32 mg IV 没有预防给予皮质类固醇 病人14天后进行评估,Gralla 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
11、.75 mg (n=189) Ondansetron 32 mg (n=185),*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.,治疗失败时间,Time (h),10,20,0,3
12、0,40,50,60,70,80,90,100,0,24,48,72,96,120,Percent of Patients,Palonosetron 0.25 mg (n=223),Palonosetron 0.75 mg (n=223),Ondansetron 32 mg (n=221),P=NS for palonosetron 0.25 mg or 0.75 mg vs ondansetron.,Time to Treatment Failure = time to 1st emetic episode or use of rescue medication.,PALO-99-05 HEC,III期临床帕洛诺司琼VS多拉司琼,Eisenberg P,Cancer，2003;98:24732482.,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 3mg,1次用药 7天观察,
