奧氮平腫瘤科應(yīng)用

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(lèi)化療藥物的劑量化療方案和給藥途徑患者的個(gè)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(huì)議達(dá)成共識(shí),確立4個(gè)致吐風(fēng)險(xiǎn)等級(jí)，先

2、后被MASCC / NCCN / ASCO 所采用,化療所致CINV的危害,對(duì)化療的不依從性水、電解質(zhì)等代謝失衡營(yíng)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(kāi)裂食管撕裂嚴(yán)重時(shí)停止治療,NCCN Clinical practice guidelines in oncology; v.2.2009: Antiemesis. NCCN, 2009.,CINV的分類(lèi),急性惡心/嘔吐 遲發(fā)性惡心/嘔吐預(yù)期性惡心

3、/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(shí)內(nèi)出現(xiàn)，一般用藥后5-6小時(shí)最高峰，24小時(shí)內(nèi)緩解。,用藥后24小時(shí)后出現(xiàn)，常于給藥后48-72 小時(shí)達(dá)最高峰，可持續(xù)6-7天。,屬條件反射，在前一次化療中出現(xiàn)惡心/嘔吐的病人，在下一次化療開(kāi)始前就出現(xiàn)惡心/嘔吐。

4、,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(shí)間分類(lèi),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 Na

5、usea and Vomiting (CINV):化療導(dǎo)致的惡心嘔吐,CINV相關(guān)神經(jīng)遞質(zhì),嘔吐中樞,Navari RM. Expert Opinion on Pharmacotherapy. 2009;10(4):629-644.,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) 受體拮抗劑:阿瑞吡坦、福沙吡坦皮質(zhì)激

6、素:地塞米松其他藥物：多巴胺拮抗劑 、苯二氮卓類(lèi)、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.,5-HT3受體拮抗劑的作用機(jī)制,奧氮平 (olanzapine),抗精神病藥物抑制

7、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,2011ASCO嘔吐指南推薦,問(wèn)題6： 輔助藥物對(duì)化療所致的惡心和嘔吐有什么樣的治療作用？ 推薦： 1、勞拉西泮和苯海拉明有用輔助止吐藥物，但不推薦 作為單獨(dú)用于止吐。 2、一個(gè)新的試驗(yàn)評(píng)價(jià)包括奧氮平止吐治療，奧氮平在 化療期間的止吐作用有明顯療效,Antiemetics: American Soc

8、iety of Clinical Oncology Clinical Practice Guideline Update 2011,,,,,,奧氮平治療遲發(fā)型嘔吐的歷程,2003年個(gè)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

9、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：CINV,A phase II trial of olanzapine for theprevention of chemotherapy-induced nausea and vomiting,Support Care Cancer (2005) 13: 529–534,,,Support

10、Care Cancer (2005) 13: 529–534,,,Support Care Cancer (2005) 13: 529–534,,用法用量,Support Care Cancer (2005) 13: 529–534,A phase II trial of olanzapine for theprevention of chemotherapy-induced nausea and vomiting,,30例

11、患者每人至少完成一個(gè)周期化療,其中：26例完成2個(gè)周期25例完成3個(gè)周期21例完成4個(gè)周期6 例完成5個(gè)周期4 例完成6個(gè)周期,Complete response,Support Care Cancer (2005) 13: 529–534,MDASI scores,Support Care Cancer (2005) 13: 529–534,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

12、,一般活動(dòng),情緒,與他人關(guān)系,,2.奧氮平、地塞米松、帕洛諾司瓊：CINV,A phase II trial of olanzapine, dexamethasone and palonosetron for the prevention of chemotherapyinducednausea and vomiting,Support Care Cancer (2007) 15:1285–1291,,,Support Care Can

13、cer (2007) 15:1285–1291,,,用法用量,A phase II trial of olanzapine, dexamethasone and palonosetron for the prevention of chemotherapyinducednausea and vomiting,Support Care Cancer (2007) 15:1285–1291,化療最多6個(gè)周期或至患者不可耐受,,40例患者每人

14、至少完成一個(gè)周期化療，其中：34 例完成2個(gè)周期30 例完成3個(gè)周期26 例完成4個(gè)周期15 例完成5個(gè)周期13 例完成6個(gè)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 high

15、ly emetogenic chemotherapy(HEC) or moderately emetogenic chemotherapy(MEC) in cycle 1,Support Care Cancer (2007) 15:1285–1291,Percent of no nausea,Fig. 2 Percent of patients with no nausea (no nausea, 0 on scale of 0–10

16、, MDASI) for patients receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in cycle 1,Support Care Cancer (2007) 15:1285–1291,MDASI 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(dòng),情

17、緒,與他人關(guān)系,生活樂(lè)趣,,3.OAD vs AD：CINV,Journal 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

18、 10 mg i.v. D1地塞米松 10 mg i.v. d1～5N=108,229例患者：首要終點(diǎn)：CR:無(wú)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, 28:131,Complete response,Clinical research of Olanza

19、pine 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

20、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 conse

21、quences 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,兩組患者均具有良好的耐受性,J

22、ournal of Experimental & Clinical Cancer Research 2009, 28:131,4.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

23、 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=120,241例患者：首要終點(diǎn)：CR:無(wú)惡心嘔吐,A Randomized Phase III Tri

24、al,J Support Oncol 2011;9:188–195,,,,J Support Oncol 2011;9:188–195,P > 0.05 for acute, delayed,and overall,,J Support Oncol 2011;9:188–195,P >0.05 for acute, P ≦ 0.01 for delayed and overall,MDASI Scores,疲勞,失眠,悲痛