奧氮平腫瘤科應(yīng)用課件

1、化療導(dǎo)致的惡心嘔吐的病理生理學(xué)影響CINV的因素化療藥物的種類化療藥物的劑量化療方案和給藥途徑患者的個人因素性別（女性患者更易嘔吐）年齡（年輕患者更易嘔吐）既往化療致吐史飲酒史（飲酒史患者不易嘔吐）NCCN Clinical practice guidelines in oncology; v.2.2009: Antiemesis. NCCN, 2009. 2004年意大利佩魯賈會議達(dá)成共識 確立4個致吐風(fēng)險(xiǎn)等級，先后被MASCC / NCCN / ASCO 所采用化療所致CINV的危害對化療的不依從性水、電解質(zhì)等代謝失衡營養(yǎng)丟失厭食自理能力受損體能與精神狀態(tài)下降創(chuàng)口愈合延遲，傷口開裂食管撕裂

2、嚴(yán)重時停止治療NCCN Clinical practice guidelines in oncology; v.2.2009: Antiemesis. NCCN, 2009. CINV的分類急性惡心/嘔吐 遲發(fā)性惡心/嘔吐預(yù)期性惡心/嘔吐突破性惡心/嘔吐難治性惡心/嘔吐NCCN Clinical practice guidelines in oncology; v.2.2009: Antiemesis. NCCN, 2009. 用藥后數(shù)分鐘到數(shù)小時內(nèi)出現(xiàn)，一般用藥后5-6小時最高峰，24小時內(nèi)緩解。用藥后24小時后出現(xiàn)，常于給藥后48-72 小時達(dá)最高峰，可持續(xù)6-7天。屬條件反射，在前一次化

3、療中出現(xiàn)惡心/嘔吐的病人，在下一次化療開始前就出現(xiàn)惡心/嘔吐。指在給予預(yù)防性止吐治療后仍出現(xiàn)且需解救治療的嘔吐指預(yù)防性和解救性止吐治療均失敗的嘔吐。CINV按時間分類預(yù)期性嘔吐Anticipatory急性嘔吐Acute 遲發(fā)性嘔吐 Delayed化療24 hours具有中高度催吐反應(yīng)的化療引起的惡心嘔吐反應(yīng)至少持續(xù)3天Chemotherapy-Induced Nausea and Vomiting (CINV):化療導(dǎo)致的惡心嘔吐CINV的治療常用的治療藥物5-HT3受體拮抗劑第一代：昂丹司瓊、格拉司瓊、托烷司瓊、雷莫司瓊、阿扎司瓊、多拉司瓊等第二代：帕洛諾司瓊NK1(神經(jīng)激肽-1) 受體拮抗

4、劑:阿瑞吡坦、福沙吡坦皮質(zhì)激素:地塞米松其他藥物：多巴胺拮抗劑 、苯二氮卓類、抗組胺藥Navari RM. Expert Opinion on Pharmacotherapy. 2009;10(4):629-644.NCCN Clinical practice guidelines in oncology; v.2.2006: Antiemesis. NCCN,2006. 奧氮平 (olanzapine)抗精神病藥物抑制多種神經(jīng)遞質(zhì)多巴胺5-羥色胺兒茶酚胺乙酰膽堿組胺奧氮平治療遲發(fā)型嘔吐的歷程2003年個案報(bào)道2004年：一期臨床2005年：二期臨床：奧氮平+格拉司瓊+地塞米松2007年：二期

5、臨床：奧氮平+帕洛諾司瓊+地塞米松2009年：三期研究：阿扎司瓊+地塞米松奧氮平2011年：三期臨床：奧氮平或阿瑞吡坦+帕洛諾司瓊+地塞米松2011年ASCO嘔吐指南推薦2012年NCCN嘔吐指南推薦歐蘭寧（奧氮平）治療CINV的相關(guān)研究！1.奧氮平、格拉司瓊、地塞米松：CINVA phase II trial of olanzapine for theprevention of chemotherapy-induced nausea and vomitingSupport Care Cancer (2005) 13: 529534Support Care Cancer (2005) 13:

6、529534用法用量Support Care Cancer (2005) 13: 529534A phase II trial of olanzapine for theprevention of chemotherapy-induced nausea and vomitingComplete responseSupport Care Cancer (2005) 13: 529534MDASI scoresSupport Care Cancer (2005) 13: 529534疲勞惡心失眠悲痛記憶力呼吸淺促食欲不振昏昏欲睡嘔吐麻木一般活動情緒與他人關(guān)系Support Care Cancer

7、(2007) 15:12851291用法用量A phase II trial of olanzapine, dexamethasone and palonosetron for the prevention of chemotherapyinducednausea and vomitingSupport Care Cancer (2007) 15:12851291化療最多6個周期或至患者不可耐受40例患者每人至少完成一個周期化療，其中：34 例完成2個周期30 例完成3個周期26 例完成4個周期15 例完成5個周期13 例完成6個周期Percent of no nauseaFig. 2 Per

8、cent 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 1Support Care Cancer (2007) 15:12851291MDASI scores疲勞惡心失眠悲痛記憶力呼吸淺促食欲不振昏昏欲睡嘔吐麻木一般活動情緒與他人關(guān)系生活樂趣3.OAD vs AD：CINVJournal

9、of Experimental & Clinical Cancer Research 2009, 28:131用法用量奧氮平 10 mg p.o. d1-5阿扎司瓊 10 mg i.v. d1地塞米松 10 mg i.v. D1N=121阿扎司瓊 10 mg i.v. D1地塞米松 10 mg i.v. d15N=108229例患者：首要終點(diǎn)：CR:無惡心嘔吐次要終點(diǎn)：生活質(zhì)量，安全性，毒性Journal of Experimental & Clinical Cancer Research 2009, 28:131Complete responseClinical research of Ol

10、anzapine for prevention ofchemotherapy-induced nausea and vomitingJournal of Experimental & Clinical Cancer Research 2009, 28:131Definition of nausea according to CTCAE V 3.0L1: Loss of appetite without alteration in eating habitsL2: Oral intake decreased without significant weight loss, dehydration

11、 or malnutrition; IV fluids, indicated 24 hrs.L3: inadequate oral caloric and/or fluid intake, IV fluids, tube feedings, or TPN indicated 24 hrsL4: Life-threatening consequences L5: DeathDefinition of nausea according to CTCAE V 3.0L1: 1 episode in 24 hrs L2: 2-5 episodes in 24 hrs; IV fluids indica

12、ted = 6 episodes in 24 hrs; IV fluids, or TPN indicated = 24 hrs L4: Life-threatening consequences L5: DeathClinical research of Olanzapine for prevention ofchemotherapy-induced nausea and vomitingJournal of Experimental & Clinical Cancer Research 2009, 28:131quality of life兩組患者均具有良好的耐受性Journal of E

13、xperimental & Clinical Cancer Research 2009, 28:1314.奧氮平 VS 阿瑞吡坦 :CINV奧氮平 10 mg p.o. d1-4帕洛諾司瓊 0.25mg i.v. d1,化療前30-60min地塞米松 20mg i.v. D1N=121阿瑞吡坦 125mg p.o ,d1 80mg p.o ,d2、3帕洛諾司瓊 0.25mg i.v. d1地塞米松 12mg i.v. D1 4mg,bid,p.o.，d2-4N=120241例患者：首要終點(diǎn)：CR:無惡心嘔吐 A Randomized Phase III TrialJ Support Oncol 2011;9:188195J Support Oncol 2011;9:1881