Sato Junya, Kashiwaba Masahiro, Komatsu Hideaki, Ishida Kazushige, Nihei Satoru, Kudo Kenzo
Department of Pharmacy, Iwate Medical University Hospital, Morioka Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Iwate Medical University, Morioka.
Department of Surgery, Faculty of Medicine, Iwate Medical University, Morioka, Japan
Jpn J Clin Oncol. 2016 May;46(5):415-20. doi: 10.1093/jjco/hyw011. Epub 2016 Mar 6.
Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated.
Forty-five patients with breast cancer who experienced >Grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle.
As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P < 0.05). As the secondary endpoints, mean nausea scale (3.2→1.9, Day 1; 3→1.3-1, Days 2-6) and dietary intake (33.6→53.8%, Day 1; 42.0→60.7-78.1%, Days 2-6) were improved by adding olanzapine. Only four patients withdrew due to somnolence and/or dizziness.
This study demonstrated the effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant.
神经激肽1受体阻滞剂、5-羟色胺受体阻滞剂和类固醇的三联止吐疗法常用于化疗后呕吐严重的患者。然而,对于三联止吐疗法耐药的患者,尚未确立替代的止吐疗法。奥氮平在指南中被推荐为一种可选的止吐药物。然而,在三联止吐疗法中添加奥氮平的有效性尚不清楚。在本研究中,前瞻性地调查了在以阿瑞匹坦、帕洛诺司琼和地塞米松进行三联止吐疗法的基础上添加奥氮平,用于原发性乳腺癌患者含蒽环类药物的高致吐辅助化疗时的有效性和安全性。
纳入45例在使用表柔比星和环磷酰胺进行的首个化疗周期后出现1级以上恶心或任何呕吐情况的乳腺癌患者。从化疗第一天起口服低剂量奥氮平(2.5毫克/天),持续4天,并将呕吐发作次数、恶心程度、饮食摄入量和嗜睡情况与首个化疗周期后的症状进行比较。
作为主要终点,添加奥氮平后恶心程度显著改善(P<0.05)。作为次要终点,添加奥氮平后平均恶心程度(第1天:3.2→1.9;第2 - 6天:3→1.3 - 1)和饮食摄入量(第1天:33.6→53.8%;第2 - 6天:42.0→60.7 - 78.1%)得到改善。仅有4例患者因嗜睡和/或头晕退出。
本研究证明了对于采用帕洛诺司琼、类固醇和阿瑞匹坦组成的三联止吐疗法后恶心缓解不足的患者,添加低剂量奥氮平的有效性和耐受性。