CHICAGO (EGMN) – Olanzapine, an atypical antipsychotic used in the treatment of schizophrenia and other psychiatric disorders, may also have a role in the management of chemotherapy-induced nausea and vomiting, a randomized phase III trial found.

The 61 patients receiving highly emetogenic chemotherapy were about twice as likely not to experience any delayed nausea with an olanzapine regimen compared with a standard aprepitant regimen (68% vs. 37%), investigators reported at the annual meeting of the American Society of Clinical Oncology.

The two regimens worked similarly well for preventing acute nausea and for preventing both acute and delayed vomiting. In addition, both had good safety profiles.

“In the control of nausea, the olanzapine regimen was much more effective,” said lead investigator Dr. Rudolph M. Navari of the University of Notre Dame’s Walther Cancer Research Institute and Indiana University, both in South Bend.

“Control of nausea is one of the big areas that we need to improve on,” he said in an interview. “Our current antiemetics are pretty good for controlling emesis, but we still have a long ways to go in controlling nausea.”

The investigators enrolled 61 adult chemotherapy-naive outpatients who were starting a course of highly emetogenic chemotherapy. The patients were randomly assigned in nearly equal numbers to receive either an olanzapine or aprepitant regimen.

The olanzapine regimen consisted of 10 mg of oral olanzapine, 0.25 mg of IV palonosetron, and 20 mg of IV dexamethasone on day 1, followed by 10 mg/day of oral olanzapine on days 2-4. (Note: Olanzapine is not indicated for nausea control.)

The aprepitant regimen – the standard one recommended in ASCO guidelines, Dr. Navari noted – consisted of 125 mg of oral aprepitant, 0.25 mg of IV palonosetron, and 12 mg of IV dexamethasone on day 1, followed by 80 mg/day of oral aprepitant on days 2 and 3, and 4 mg BID of oral dexamethasone on days 2-4.

The investigators assessed rates of complete response (defined as no emetic episodes and no use of rescue medication) and rates of nausea control (defined as no nausea), as indicated by a score of 0 on the 10-point MDASI (M.D. Anderson Symptom Inventory), both in the acute period (0-24 hours) and the delayed period (24-120 hours) after chemotherapy.

According to study results, the patients had a median age of about 58 years, and 70% were women. Most had breast cancer (52%) or lung cancer (31%). The chemotherapy being given was doxorubicin-cyclophosphamide (64%) and cisplatin (36%).

During cycle 1 of chemotherapy, patients in the olanzapine and aprepitant groups did not differ significantly with respect to the rate of complete response to their antiemetic regimen in the acute period (100% vs. 90%, respectively) or in the delayed period (77% vs. 73%, respectively), Dr. Navari reported in a poster session at the meeting.

Patients in the olanzapine and aprepitant groups also did not differ significantly with respect to the rate of nausea control in the acute period (90% vs. 87%). However, patients in the olanzapine group had a higher rate of nausea control in the delayed period (68% vs. 37%; P less than .01).

The severity of 11 other symptoms and the extent of symptom interference with six daily activities on days 1 and 5 after chemotherapy – also rated with the MDASI – were low to moderate. None of the patients experienced grade 3 or 4 toxicity.

“Both of these regimens have few side effects,” Dr. Navari commented. In particular, he noted, the adverse effects of olanzapine seen with long-term use in the psychiatric population do not appear to manifest with short-term use in this population.

The efficacy and safety findings seen in cycle 1 were maintained during cycles 2-4 of chemotherapy, with rates of complete response and control of nausea equal to or greater than those in cycle 1 for each group.

“Olanzapine seems to be a promising, effective agent for controlling not only emesis, but also nausea in this patient population, which is at high risk for chemotherapy-induced nausea and vomiting,” concluded Dr. Navari.

The reason for its superiority when it comes to nausea control in the delayed period is uncertain, he said. “We do know that it works in the central nervous system, and it blocks a number of receptors: [serotonin] 5-HT receptors, muscarinic receptors, dopamine receptors, and probably some other receptors,” he explained. But “we don’t know the exact mechanism.”

Dr. Navari reported that he had no relevant conflicts of interest.

Copyright (c) 2010 Elsevier Global Medical News. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.

芝加哥(EGMN)——一项III期随机试验显示，用于治疗精神分裂症和其他精神障碍的非典型抗精神病药奥氮平对化疗性恶心和呕吐具有一定的治疗作用。

 

研究者在美国临床肿瘤学会(ASCO)年会上指出，在61例接受高致吐性化疗的患者中，奥氮平方案控制延迟性恶心的作用约为标准阿瑞吡坦方案的两倍(延迟期恶心控制率为68%对37%)。

 

这两种方案在预防急性恶心、急性呕吐和延迟性呕吐方面具有相似的良好效果。此外，两种方案均具有良好安全性。

 

南本德圣母大学Walther 癌症研究所和印第安纳大学的Rudolph M. Navari博士是该研究的主要研究者，他表示：“在控制恶心方面，奥氮平方案明显更有效。”

 

他在接受采访时说：“控制恶心是我们需要改善的重要方面之一。现有止吐药的止吐效果都非常好，但在控制恶心方面仍有很长的路要走。”

 

该研究招募了61例正开始接受高致吐性化疗的成人门诊患者(此前均未接受过化疗)。 患者被随机且几乎均等地分入两组：奥氮平方案组和阿瑞吡坦方案组。

 

奥氮平方案为第1天给予10 mg口服奥氮平、0.25 mg静脉(IV)帕洛诺司琼和20 mg IV地塞米松，第2~4天给予10 mg/天口服奥氮平(注：奥氮平的适应证并非控制恶心)。

 

Navari博士指出，阿瑞吡坦方案(ASCO指南推荐的标准方案)为第1天给予125 mg口服阿瑞吡坦、0.25 mg IV帕洛诺司琼和12 mg IV地塞米松，第2~3天给予80 mg/天口服阿瑞吡坦，第2~4天给予4 mg 口服地塞米松，每日2次。

 

研究者采用10分制M.D. Anderson 症状量表(MDASI)在化疗后急性期(0~24 h)和延迟期(24~120 h)对完全缓解(定义为无呕吐及未使用解救药物，MADSI评分为0)率和恶心控制(定义为无恶心，MADSI评分为0)率进行评价。

 

在该研究中，患者的中位年龄约为58岁，70%为女性。大部分为乳腺癌(52%) 或肺癌 (31%)患者。化疗药物包括阿霉素-环磷酰胺(64%)和顺铂(36%)。

 

Navari博士在该会议的壁报展示会上表示，在第1个化疗周期内，奥氮平组与阿瑞吡坦组急性期(100%对90%)和延迟期(77% 对73%)的完全有效率均无显著差异。

 

奥氮平组与阿瑞吡坦组急性期(90%对87%)的恶心控制率亦无显著差异。然而，奥氮平组延迟期的恶心控制率高于阿瑞吡坦组 (68%对37%；P < 0.01)。

 

化疗后第1天和第5天，同样采用MDASI评定的其他11种症状的严重程度及症状对6种日常活动的影响程度均为轻至中度。在患者中未观察到3级或4级毒性事件。

 

Navari博士说：“这两种方案的不良反应较少。” 他特别指出，在长期使用奥氮平的精神病人群中观察到的不良反应并未见于短期使用奥氮平的这一患者人群。

 

在化疗第1个周期内观察到的疗效和安全性结果在第2~4个周期内维持不变：各组第2~4个周期内的完全有效率和恶心控制率等于或高于第1周期内的完全有效率和恶心控制率。

 

Navari博士总结说：“在发生化疗性恶心和呕吐风险较高的这一患者人群中，奥氮平似乎不仅可有效控制呕吐，也可有效控制恶心。”

 

他表示，尚不清楚为什么奥氮平对延迟期恶心的控制作用更佳。他解释说：“我们知道，该药作用于中枢神经系统，并阻断许多受体：5-羟色胺(5-HT)受体、毒蕈碱受体、多巴胺受体和可能其他一些受体。但“我们并不知道确切的机制。”

 

Navari 博士声明其没有任何相关经济利益冲突。

 

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