BACKGROUND Treatment options are limited for recurrent nasopharyngeal carcinoma (NPC). We report results from a phase II study of CC-486 (oral azacitidine) in advanced NPC. PATIENTS AND METHODS Patients with locally advanced or metastatic NPC and 1-2 prior treatment regimens received CC-486 300 mg daily on days 1-14 of 21-day cycles until disease progression or unacceptable toxicity. The first 6 patients of Asian-Pacific Islander (API) ethnicity received a reduced dose of 200 mg to preserve safety and tolerability; if well tolerated, subsequent API patients received CC-486 300 mg. The study could advance to stage 2 if > 4 patients achieved a response. Co-primary end-points were overall response rate (ORR) and progression-free survival (independent review). Key secondary end-points were overall survival and safety. RESULTS Owing to faster-than-anticipated enrolment, 36 patients, including 13 of API ethnicity, were enrolled; the median age was 54.0 years. Most patients were male (81%) and had an Eastern Cooperative Oncology Group performance status ≤ 1 (97%). Among 25 efficacy-evaluable patients, the ORR was 12%; the median progression-free and overall survival were 4.7 and 18.0 months, respectively. The most common grade III/IV treatment-emergent adverse events were neutropenia (33%) and febrile neutropenia (11%). Twenty-one posttreatment deaths, primarily due to progressive disease or disease complications, and 1 on-treatment death (epistaxis, unrelated to study drug) occurred. The study did not advance to stage 2. CONCLUSION CC-486 did not show sufficient clinical activity to support further development as monotherapy in this patient population. The safety profile of CC-486 in NPC was consistent with that in other solid tumours.

中文翻译：

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在先前治疗过的局部晚期或转移性鼻咽癌患者中CC-486（口服阿扎胞苷）的II期研究。

背景技术复发性鼻咽癌（NPC）的治疗选择受到限制。我们报告了晚期NPC中CC-486（口服阿扎胞苷）的II期研究结果。患者和方法患有局部晚期或转移性NPC且有1-2种先前治疗方案的患者在21天周期的第1-14天每天接受CC-486 300 mg，直到疾病进展或出现不可接受的毒性。为保护安全性和耐受性，亚太岛民（API）族的前6名患者减少了200 mg的剂量；如果耐受性良好，则随后的API患者将接受CC-486 300 mg。如果> 4位患者获得了缓解，则该研究可以进入第2阶段。共同主要终点是总体缓解率（ORR）和无进展生存期（独立评价）。主要的次要终点是总体生存率和安全性。结果由于入组速度快于预期，招募了36名患者，其中包括13名API种族。中位年龄是54.0岁。大多数患者为男性（81％），并且东部合作肿瘤小组的工作状态≤1（97％）。在25例可评估疗效的患者中，ORR为12％。中位无进展生存期和总生存期分别为4.7和18.0个月。最常见的III / IV级治疗突发事件为中性粒细胞减少症（33％）和高热性中性粒细胞减少症（11％）。主要由于进行性疾病或疾病并发症造成的21个治疗后死亡和1个治疗中死亡（鼻塞，与研究药物无关）发生。该研究尚未进入第2阶段。结论CC-486没有显示出足够的临床活性来支持该患者人群单药治疗的进一步发展。