Yeo Winnie, Mo F K F, Suen J J S, Ho W M, Chan S L, Lau W, Koh J, Yeung W K, Kwan W H, Lee K K C, Mok T S K, Poon A N Y, Lam K C, Hui E K, Zee B
Department of Clinical Oncology, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Breast Cancer Res Treat. 2009 Feb;113(3):529-35. doi: 10.1007/s10549-008-9957-9. Epub 2008 Mar 10.
This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients.
Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE).
Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, 'no vomiting', 'no significant nausea' and 'no nausea'. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 [30.79]) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade >or= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048).
The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.
这是一项单中心、随机、双盲、安慰剂对照研究，旨在评估NK(1)受体拮抗剂阿瑞匹坦对中国乳腺癌患者的疗效。主要目的是比较以阿瑞匹坦为基础的止吐方案与标准止吐方案在接受中度致吐性化疗的患者中预防化疗引起的恶心和呕吐（CINV）的疗效。次要目的是比较这两组患者报告的生活质量。
符合条件的乳腺癌患者为初治患者，接受辅助AC化疗（即阿霉素60mg/m²和环磷酰胺600mg/m²）。患者被随机分配到以阿瑞匹坦为基础的方案组（第1天，化疗前给予阿瑞匹坦125mg、昂丹司琼8mg和地塞米松12mg，8小时后给予昂丹司琼8mg；第2至3天，阿瑞匹坦80mg每日一次）或对照组，对照组采用标准方案（第1天，化疗前给予昂丹司琼8mg和地塞米松20mg，8小时后给予昂丹司琼8mg；第2至3天，昂丹司琼8mg每日两次）。通过自我报告日记收集恶心、呕吐和使用解救药物的数据，采用自我管理的功能性生活指数-呕吐（FLIE）评估患者的生活质量。
127例随机分组的患者中，124例可评估。在第1周期AC化疗的CINV方面，报告完全缓解、完全保护、完全控制、“无呕吐”、“无明显恶心”和“无恶心”的患者比例无显著差异。与标准方案组相比，以阿瑞匹坦为基础的方案组患者对解救药物的需求似乎更少（11%对20%；P = 0.06）。FLIE评估显示，两组在恶心领域和总分方面无差异；然而，接受标准止吐方案的患者在呕吐领域的生活质量明显较差（平均得分[标准差]=23.99[30.79]），而接受以阿瑞匹坦为基础的方案的患者（平均得分[标准差]=3.40[13.18]）（P = 0.0002）。两种治疗的耐受性一般都较好。接受以阿瑞匹坦为基础的方案治疗的患者中性粒细胞减少症的发生率显著较低（53.2%对35.5%，P = 0.0468），≥3级中性粒细胞减少症的发生率较低（21.0%对45.2，P = 0.0042），后续化疗周期延迟的发生率较低（8.1%对出27.4%，P = 0.0048）。
与对照方案相比，阿瑞匹坦方案在接受蒽环类药物和环磷酰胺治疗的患者中预防CINV时似乎可减少对解救药物的需求，并且在辅助AC化疗期间与更好的生活质量相关。
