奥氮平预防高致吐性化疗方案致恶心呕吐的临床观察

Clinical observation of olanzapine in prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogetic chemotherapy

目的评价奥氮平预防含顺铂、表阿霉素的高致吐性化疗方案所致恶心呕吐(CINV)的有效性和安全性。方法对符合纳入标准的52例恶性肿瘤患者应用高致吐性方案化疗2个周期,随机交叉应用A→B方案或B→A方案进行预防性止呕处理。A方案(空白对照组):盐酸帕洛诺司琼0.25 mg d_1+地塞米松10 mg d_1~d_3,静推;B方案(奥氮平组):A方案基础上,加用奥氮平10 mg d_(-1)~d_5,睡前口服。主要研究指标为患者化疗后5天内急性(0~24 h)及延迟性(25~120 h)恶心、呕吐的完全缓解(CR)率,同时评估奥氮平治疗的安全性。结果最终完成2个周期化疗并可评价疗效的患者共50例,脱落2例。奥氮平组与空白对照组比较,在急性恶心(88.0%vs.52.0%,P<0.05)、延迟性恶心(72.0%vs.20.0%,P<0.05)、延迟性呕吐(86.0%vs.64.0%,P<0.05)方面CR率更高的,而在急性呕吐方面两组CR率的差异无统计学意义(94.0%vs.86.0%,P>0.05)。奥氮平止呕相关不良反应包括头晕、嗜睡、口干、疲劳、便秘、直立性低血压等,均少见且程度较轻,组间差异无统计学意义(P>0.05)。结论在盐酸帕洛诺司琼和地塞米松的基础上,加入奥氮平可以有效地提高高致吐性化疗方案致急性恶心、延迟性恶心与呕吐的疗效,且安全性较好。

Objective To evaluate the efficiency and safety of olanzapine in acute and delayed chemotherapy-induced nausea and vomiting （CINV） among Chinese cancer patients who received highly emetogenic chemotherapy.Methods This experiment was designed as a randomized, self-crossover and blank control clinical trial.Two sequential cycles of highly emetogenic chemotherapy were carried out on 52 cases of malignant tumor patients who met the inclusion criterion.All the patients received a sequential A/B or B/A chemotherapy cycle randomly.In cycle A （blank control group）, each patient should receive the standard anti-nausea treatment by intravenous injection 30 minutes before chemotherapy, including palonosetron （0.25 mg, d1） and dexamethasone （10 mg, d1-d3）.In chemotherapy cycle B （olanzapine group）, patients not only received standard anti-nausea treatment like cycle A, but also a additional olanzapine treatment （10 mg po, qn） from the day before chemotherapy to the fifth day after chemotherapy administration.The primary endpoint in this study was the complete control rate of the nausea and vomiting happened within 5 days after chemotherapy administration, and the second endpoint was the safety of anti-nausea treatment.Results A total of 50 patients could be evaluated who fulfilled two different cycles of chemotherapy, and another 2 patients dropped out.When compared with non-olanzapine group, olanzapine group had a higher complete control rate of acute nausea （88.0% vs.52.0%, P〈0.05）, delayed nausea （72.0% vs.20.0%, P〈0.05）, and delayed vomiting （86.0% vs.64.0%, P〈0.05）.However, olanzapine group and non-olanzapine group both had a high complete control rate of acute vomiting （94.0% vs.86.0%）, but there was no significant difference（P〉0.05）.The main adverse effects suffered by patient in this trial included dizziness, somnolence, dry mouth, fatigue, constipation and orthostatic hypotension.The proportion and degree of adverse effect in olanzapine group and non-olanzapine group were very low, and there was no significant statistical difference between two groups（P〉0.05）.Conclusion Olanzapine can further improve the control efficiency of CINV based on the standard treatment of palonosetron and dexamethasone without increasing the adverse effect of treatment.