Objective To investigate the maximum tolerated dose of olanzapine for preventing emesis and nausea during chemotherapy in cancer patients.Methods This study was designed with olanzapine,using a six-cohort dose escalation of at least 3 patients per cohort,combining granisetron and dexamethasone for the prevention of chemotherapy-induced emesis and nausea in cancer patients.The initial dose cohort of olanzapine was 2.5mg; the terminal one was 20mg.Olanzapine was administered from one day before experiment to 14th day of experiment(d-1-d14) per night.If no dose-limiting toxicity was observed,the study could escalate to the next cohort.Results Eighteen patients were enrolled in the protocol and fifteen patients completed it.Two patient experienced a doselimiting toxicity(grade 3) of dry mouth and somnolence in 15mg cohort.Thus the study stopped on this cohort.In this study adverse events above grade 2 were somnolence,sedation,dizziness,akathisia,constipation,fatigue and bone marrow suppression.Conclusion Olanzapine is well tolerated and safe in using recommended dose 15mg on d-1 to d14 per night.%目的 探讨奥氮平联合格拉司琼和地塞米松预防化疗所致恶心、呕吐的最大耐受剂量.方法 奥氮平设6个剂量水平,分别为2.5、5、7.5、10、15和20mg,联合格拉司琼和地塞米松进行治疗,每个剂量组至少3例受试者.初始剂量为奥氮平2.5mg,每晚1次,试验前1天至试验第14天(d-1～d14)；如无方案规定的剂量限制性毒性(LTD)则进入下一剂量组,直至观察到最大耐受剂量(MTD),若20mg组未出现MTD不再增加剂量.结果 18例肿瘤患者纳入试验,依次进行了前5个剂量组的研究；在进行15mg剂量组的3例患者中出现1例3级口干,后追加2例患者出现1例3级嗜睡,试验终止于此剂量组.2级及以上的不良反应主要为嗜睡、头晕、静坐不能、口干、便秘、疲劳和骨髓抑制.结论 奥氮平长期使用(口服15天)的耐受性好,安全性高,推荐剂量为10mg,每晚1次,d-1～d14.
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