A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens
A Phase II, open-label, randomised study to assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) versus capecitabine monotherapy in patients with colorectal cancer who have failed one or two prior chemotherapeutic regimens
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DOI：
10.1007/s10637-010-9392-8
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发表时间：
2011-10-01
影响因子：
3.4
通讯作者：
Douillard, Jean-Yves
中科院分区：
文献类型：
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作者：
Bennouna, Jaafar;Lang, Istvan;Douillard, Jean-Yves
目的评估MEK 1/2抑制剂AZD 6244（ARRY-142886）在既往1或2种化疗方案（包括奥沙利铂和/或伊立替康）失败的转移性结直肠癌患者中的疗效和安全性。方法这是一项比较AZD 6244与卡培他滨单药治疗的II期、多中心、开放标签、随机、双臂、平行组研究。患者接受100 mg每日两次口服AZD 6244游离碱混悬液或1，250 mg/m2每日两次口服卡培他滨，持续2周，随后停药1周，每3周为1个周期。主要终点是发生疾病进展事件的患者数量。结果69例患者在研究中接受了随机化（AZD 6244组和卡培他滨组分别有34例和35例患者）。AZD 6244和卡培他滨治疗组均有28例患者（相似于80%）发生疾病进展事件。AZD 6244组和卡培他滨组的中位无进展生存期分别为81天和88天。AZD 6244治疗组中有10例患者的最佳缓解为疾病稳定。对于卡培他滨，1例患者的最佳缓解为部分缓解，另外15例患者病情稳定。AZD 6244组最常见的不良事件为痤疮样皮炎、腹泻、虚弱和外周水肿，而卡培他滨组则为手足综合征、腹泻、恶心和腹痛。结论AZD 6244在发生疾病进展事件的患者数量和无进展生存期方面与卡培他滨相似。AZD 6244目前正在与其他化疗药物联合进行II期试验评估。
Objectives To assess the efficacy and safety of the MEK1/2 inhibitor AZD6244 (ARRY-142886) in patients with metastatic colorectal cancer who had failed one or two previous chemotherapeutic regimens that included oxaliplatin and/or irinotecan. Methods This was a Phase II, multicentre, open-label, randomised, two-arm, parallel-group study comparing AZD6244 with capecitabine monotherapy. Patients received either 100 mg twice daily oral AZD6244 free-base suspension every day or 1,250 mg/m(2) twice daily oral capecitabine, for 2 weeks, followed by a 1-week rest period, in 3-weekly cycles. The primary endpoint was the number of patients experiencing disease progression events. Results Sixty-nine patients were randomised in the study (34 and 35 patients in the AZD6244 and capecitabine groups, respectively). Disease progression events were experienced by 28 patients (similar to 80%) in both the AZD6244 and capecitabine treatment groups. Median progression-free survival was 81 days and 88 days in the AZD6244 and capecitabine groups, respectively. Ten patients in the AZD6244 treatment arm had a best response of stable disease. For capecitabine, best response was a partial response in one patient, with stable disease in a further 15 patients. The most frequently observed adverse events reported with AZD6244 were acneiform dermatitis, diarrhoea, asthenia and peripheral oedema, compared with hand-foot syndrome, diarrhoea, nausea and abdominal pain with capecitabine. Conclusions AZD6244 showed similar efficacy to capecitabine in terms of the number of patients with a disease progression event and of progression-free survival. AZD6244 is currently undergoing evaluation in Phase II trials in combination with other chemotherapeutic agents.