奥氮平肿瘤科应用

化疗导致的恶心呕吐的病理生理学,影响CINV的因素,化疗药物的种类化疗药物的剂量化疗方案和给药途径患者的个人因素性别（女性患者更易呕吐）年龄（年轻患者更易呕吐）既往化疗致吐史饮酒史（饮酒史患者不易呕吐）,NCCN Clinical practice guidelines in oncology; v.2.2009: Antiemesis. NCCN, 2009.,2004年意大利佩鲁贾会议达成共识,确立4个致吐风险等级，先后被MASCC / NCCN / ASCO 所采用,化疗所致CINV的危害,对化疗的不依从性水、电解质等代谢失衡营养丢失厌食自理能力受损体能与精神状态下降创口愈合延迟，伤口开裂食管撕裂严重时停止治疗,NCCN Clinical practice guidelines in oncology; v.2.2009: Antiemesis. NCCN, 2009.,CINV的分类,急性恶心/呕吐 迟发性恶心/呕吐预期性恶心/呕吐突破性恶心/呕吐难治性恶心/呕吐,NCCN Clinical practice guidelines in oncology; v.2.2009: Antiemesis. NCCN, 2009.,用药后数分钟到数小时内出现，一般用药后5-6小时最高峰，24小时内缓解。,用药后24小时后出现，常于给药后48-72 小时达最高峰，可持续6-7天。,属条件反射，在前一次化疗中出现恶心/呕吐的病人，在下一次化疗开始前就出现恶心/呕吐。,指在给予预防性止吐治疗后仍出现且需解救治疗的呕吐,指预防性和解救性止吐治疗均失败的呕吐。,CINV按时间分类,预期性呕吐Anticipatory,急性呕吐Acute,迟发性呕吐 Delayed,化疗,24 hours,具有中高度催吐反应的化疗引起的恶心呕吐反应至少持续3天,Chemotherapy-Induced Nausea and Vomiting (CINV):化疗导致的恶心呕吐,CINV相关神经递质,呕吐中枢,Navari RM. Expert Opinion on Pharmacotherapy. 2009;10(4):629-644.,CINV的治疗,常用的治疗药物5-HT3受体拮抗剂第一代：昂丹司琼、格拉司琼、托烷司琼、雷莫司琼、阿扎司琼、多拉司琼等第二代：帕洛诺司琼NK1(神经激肽-1) 受体拮抗剂:阿瑞吡坦、福沙吡坦皮质激素:地塞米松其他药物：多巴胺拮抗剂 、苯二氮卓类、抗组胺药,Navari RM. Expert Opinion on Pharmacotherapy. 2009;10(4):629-644.NCCN Clinical practice guidelines in oncology; v.2.2006: Antiemesis. NCCN,2006.,5-HT3受体拮抗剂的作用机制,奥氮平 (olanzapine),抗精神病药物抑制多种神经递质多巴胺5-羟色胺儿茶酚胺乙酰胆碱组胺,2011ASCO呕吐指南推荐,问题6： 辅助药物对化疗所致的恶心和呕吐有什么样的治疗作用？ 推荐： 1、劳拉西泮和苯海拉明有用辅助止吐药物，但不推荐 作为单独用于止吐。 2、一个新的试验评价包括奥氮平止吐治疗，奥氮平在 化疗期间的止吐作用有明显疗效,Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update 2011,奥氮平治疗迟发型呕吐的历程,2003年个案报道2004年：一期临床2005年：二期临床：奥氮平+格拉司琼+地塞米松2007年：二期临床：奥氮平+帕洛诺司琼+地塞米松2009年：三期研究：阿扎司琼+地塞米松奥氮平2011年：三期临床：奥氮平或阿瑞吡坦+帕洛诺司琼+地塞米松2011年ASCO呕吐指南推荐2012年NCCN呕吐指南推荐,欧兰宁（奥氮平）治疗CINV的相关研究！,1.奥氮平、格拉司琼、地塞米松：CINV,A phase II trial of olanzapine for theprevention of chemotherapy-induced nausea and vomiting,Support Care Cancer (2005) 13: 529534,Support Care Cancer (2005) 13: 529534,Support Care Cancer (2005) 13: 529534,用法用量,Support Care Cancer (2005) 13: 529534,A phase II trial of olanzapine for theprevention of chemotherapy-induced nausea and vomiting,30例患者每人至少完成一个周期化疗,其中：26例完成2个周期25例完成3个周期21例完成4个周期6 例完成5个周期4 例完成6个周期,Complete response,Support Care Cancer (2005) 13: 529534,MDASI scores,Support Care Cancer (2005) 13: 529534,疲劳,恶心,失眠,悲痛,记忆力,呼吸浅促,食欲不振,昏昏欲睡,呕吐,麻木,一般活动,情绪,与他人关系,2.奥氮平、地塞米松、帕洛诺司琼：CINV,A phase II trial of olanzapine, dexamethasone and palonosetron for the prevention of chemotherapyinducednausea and vomiting,Support Care Cancer (2007) 15:12851291,Support Care Cancer (2007) 15:12851291,用法用量,A phase II trial of olanzapine, dexamethasone and palonosetron for the prevention of chemotherapyinducednausea and vomiting,Support Care Cancer (2007) 15:12851291,化疗最多6个周期或至患者不可耐受,40例患者每人至少完成一个周期化疗，其中：34 例完成2个周期30 例完成3个周期26 例完成4个周期15 例完成5个周期13 例完成6个周期,complete response,Fig. 1 Percent of patients with a complete response (no emetic episodes and no use of rescue medication) for patients receiving highly emetogenic chemotherapy(HEC) or moderately emetogenic chemotherapy(MEC) in cycle 1,Support Care Cancer (2007) 15:12851291,Percent of no nausea,Fig. 2 Percent of patients with no nausea (no nausea, 0 on scale of 010, MDASI) for patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in cycle 1,Support Care Cancer (2007) 15:12851291,MDASI scores,疲劳,恶心,失眠,悲痛,记忆力,呼吸浅促,食欲不振,昏昏欲睡,呕吐,麻木,一般活动,情绪,与他人关系,生活乐趣,3.OAD vs AD：CINV,Journal of Experimental & Clinical Cancer Research 2009, 28:131,用法用量,奥氮平 10 mg p.o. d1-5阿扎司琼 10 mg i.v. d1地塞米松 10 mg i.v. D1N=121,阿扎司琼 10 mg i.v. D1地塞米松 10 mg i.v. d15N=108,229例患者：首要终点：CR:无恶心呕吐次要终点：生活质量，安全性，毒性,Journal of Experimental & Clinical Cancer Research 2009, 28:131,Complete response,Clinical research of Olanzapine for prevention ofchemotherapy-induced nausea and vomiting,Journal of Experimental & Clinical Cancer Research 2009, 28:131,Definition of nausea according to CTCAE V 3.0L1: Loss of appetite without alteration in eating habitsL2: Oral intake decreased without significant weight loss, dehydration or malnutrition; IV fluids, indicated = 6 episodes in 24 hrs; IV fluids, or TPN indicated = 24 hrs L4: Life-threatening consequences L5: Death,Clinical research of Olanzapine for prevention ofchemotherapy-induced nausea and vomiting,Journal of Experimental & Clinical Cancer Research 2009, 28:131,quality of life,两组患者均具有良好的耐受性,Journal of Experimental & Clinical Cancer Research 2009, 28:131,4.奥氮平 VS 阿瑞吡坦 :CINV,奥氮平 10 mg p.o. d1-4帕洛诺司琼 0.25mg i.v. d1,化疗前30-60min地塞米松 20mg i.v. D1N=121,阿瑞吡坦 125mg p.o ,d1 80mg p.o ,d2、3帕洛诺司琼 0.25mg i.v. d1地塞米松 12mg i.v. D1 4mg,bid,p.o.，d2-4N=120,241例患者：首要终点：CR:无恶心呕吐,A Randomized Phase III Trial,J Support Oncol 2011;9:188195,J Support O