摘要

Older patients with acute myeloid leukemia (AML) respond poorly to standard induction therapy. B-cell lymphoma 2 (BCL-2) overexpression is implicated in survival of AML cells and treatment resistance. We report safety and efficacy of venetoclax with decitabine or azacitidine from a large, multicenter, phase 1b dose-escalation and expansion study. Patients (N = 145) were at least 65 years old with treatment-naive AML and were ineligible for intensive chemotherapy. During dose escalation, oral venetoclax was administered at 400, 800, or 1200 mg daily in combination with either decitabine (20 mg/m2, days 1-5, intravenously [IV]) or azacitidine (75 mg/m2, days 1-7, IV or subcutaneously). In the expansion, 400 or 800 mg venetoclax with either hypomethylating agent (HMA) was given. Median age was 74 years, with poor-risk cytogenetics in 49% of patients. Common adverse events (>30%) included nausea, diarrhea, constipation, febrile neutropenia, fatigue, hypokalemia, decreased appetite, and decreased white blood cell count. No tumor lysis syndrome was observed. With a median time on study of 8.9 months, 67% of patients (all doses) achieved complete remission (CR) + CR with incomplete count recovery (CRi), with a CR + CRi rate of 73% in the venetoclax 400 mg + HMA cohort. Patients with poor-risk cytogenetics and those at least 75 years old had CR + CRi rates of 60% and 65%, respectively. The median duration of CR + CRi (all patients) was 11.3 months, and median overall survival (mOS) was 17.5 months; mOS has not been reached for the 400-mg venetoclax cohort. The novel combination of venetoclax with decitabine or azacitidine was effective and well tolerated in elderly patients with AML (This trial was registered at www.clinicaltrials.gov as #NCT02203773).

译文

老年急性髓系白血病 (AML) 患者对标准诱导治疗反应不佳。B细胞淋巴瘤 2 (BCL-2) 过表达与 AML 细胞的存活和治疗抗性有关。我们报告了一项大型、多中心、 1b 期剂量递增和扩展研究中使用地西他滨或阿扎胞苷的 venetoclax 的安全性和有效性。患者 (N = 145) 至少 65 岁,未接受治疗的 AML 患者,没有资格接受强化化疗。在剂量增加期间,口服 venetoclax 每天 400 、 800 或 1200 毫克与地西他滨 (20 毫克/平方米,第 1-5 天,静脉注射 [IV]) 或阿扎胞苷 (75 mg/m2,第 1-7 天,静脉注射或皮下注射)。在膨胀过程中,给予 400 或 800 毫克的 venetoclax 和亚甲基化剂 (HMA)。中位年龄为 74 岁,49% 的患者细胞遗传学风险较低。常见的不良反应 (> 30%) 包括恶心、腹泻、便秘、发热性中性粒细胞减少、疲劳、低钾血症、食欲下降和白细胞计数下降。未观察到肿瘤溶解综合征。研究的中位时间为 8.9 个月,67% 的患者 (所有剂量) 在不完全计数恢复 (CRi) 的情况下达到完全缓解 (CR) CR, 在 venetoclax 73% mg HMA 队列中 CR CRi 率为 400。细胞遗传学风险低的患者和至少 75 岁的患者的 CRi 率分别为 60% 和 65%。CR CRi (所有患者) 的中位持续时间为 11.3 个月,中位总生存期 (mOS) 为 17.5 个月; 对于 400 mg venetoclax 队列,还没有达到 mOS。Venetoclax 与地西他滨或阿扎胞苷的新型组合对老年 AML 患者有效且耐受性良好 (该试验在 www.clinicaltrials.gov 注册为 # NCT02203773)。

Decitabine

重症 地西他滨 药物
概述  :  

地西他滨(decitabine, DCA)为5-氮杂-2'-脱氧胞嘧啶核苷,是一种胞苷的脱氧核苷类似物。其在高浓度时具有细胞毒作用,低浓度时使抑癌基因重新表达,从而发挥抗肿瘤作用。地西他滨对多种恶性血液病,包括骨髓增生异常综合征(MDS)、急性髓性白血病(AML)和慢性粒细胞白血病(CML)等均有明显疗效。   作用机制 地西他滨的主要生物学作用靶点是抑制DNA甲基化转移酶(DNA methyltransferase, DNMT),

decitabine

释义   地西他滨(药物名)

例句   Gemcitabine and decitabine have been administered in pre-clinical trials with mice. Initial findings confirm that the drugs are an effective antiviral therapy for HIV. 吉西他滨和地西他滨已用于大鼠的临床试验。初步结果证实,这些药物是一种有效的艾滋病病毒抗病毒治疗药物。

请扫描右侧二维码,免费查看词汇专业知识背景