The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy
The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy
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DOI：
10.1007/s00520-012-1710-6
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发表时间：
2013-06-01
影响因子：
3.1
通讯作者：
Gray, Sarah E.
中科院分区：
文献类型：
--
作者：
Navari, Rudolph M.;Nagy, Cindy K.;Gray, Sarah E.
奥氮平被证明是一种安全有效的预防化疗引起的恶心和呕吐（CINV）的药物。奥氮平也可能是一种有效的抢救药物，用于突破性CINV患者，尽管已接受指导的CINV预防。一项双盲、随机III期试验对接受高度致吐性化疗(顺铂，千分之一欧元70 mg/m(2)或多柔比星，千分之一欧元50 mg/m（2)和环磷酰胺，千分之一欧元600 mg/m(2)）的首次化疗患者进行了突破性CINV的治疗，比较了奥氮平和甲氧氯普胺。化疗前预防性地塞米松（静脉注射12mg）、帕洛诺司酮（静脉注射0.25 mg）、福沙匹坦（静脉注射150mg）和化疗后地塞米松（每日口服8mg，第2-4天）出现突破性呕吐或恶心的患者随机接受奥氮平（每日口服10mg，连续3天）或甲氧氯普胺（每日口服10mg，连续3天）。观察患者在服用奥氮平或甲氧氯普胺后72 h的呕吐和恶心情况。276例患者（中位年龄62岁，范围38-79岁；43%为女性；东部肿瘤合作组织（ECOG） ps0.1）同意该方案。112例患者出现突破性CINV， 108例可评估。在72小时的观察期内，56例奥氮平组患者中有39例（70%）无呕吐，52例甲氧氯普胺组患者中有16例（31%）无呕吐（p < 0.01）。观察72 h无恶心症状（0，量表0-10，M.D. Anderson症状量表）的患者中，服用奥氮平的占68%(56 / 38)，服用甲氧氯普胺的占23% (52 / 12)（p < 0.01）。没有3级或4级毒性。在高度致吐性化疗患者中，奥氮平对突破性呕吐和恶心的控制效果明显优于甲氧氯普胺。
Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis.A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, a parts per thousand yenaEuro parts per thousand 70 mg/m(2) or doxorubicin, a parts per thousand yenaEuro parts per thousand 50 mg/m(2) and cyclophosphamide, a parts per thousand yenaEuro parts per thousand 600 mg/m(2)), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38-79; 43 % women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable.During the 72-h observation period, 39 out of 56 (70 %) patients receiving olanzapine had no emesis compared to 16 out of 52 (31 %) patients with no emesis for patients receiving metoclopramide (p < 0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68 % (38 of 56), and metoclopramide, 23 % (12 of 52) (p < 0.01). There were no grade 3 or 4 toxicities.Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.