Sadashiv Santhosh K, Hilton Christie, Khan Cyrus, Rossetti James M, Benjamin Heather L, Fazal Salman, Sahovic Entezam, Shadduck Richard K, Lister John
Division of Hematology and Cellular Therapy, Allegheny Health Network, Pittsburgh, Pennsylvania, 15224.
Cancer Med. 2014 Dec;3(6):1570-8. doi: 10.1002/cam4.321. Epub 2014 Aug 16.
Acute myeloid leukemia (AML) patients aged ≥ 60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m(2)/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20-30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m(2)/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts >30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13-724 days). Grade 3-4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection-site skin reactions and fatigue (Grades 1-2), occurred in 73% (n = 11) of patients. No treatment-related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m(2)/day for 5 days every 28 days is a feasible, well-tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML.
年龄≥60岁的急性髓系白血病(AML)患者对标准诱导化疗的耐受性较差。以75 mg/m²/天的剂量使用阿扎胞苷治疗7天似乎耐受性更好,并且已获美国食品药品监督管理局(FDA)批准用于治疗骨髓(BM)原始细胞计数为20%-30%的老年AML患者。在此,我们报告一项前瞻性2期开放标签研究的结果,该研究评估了每28天给予15例新诊断AML老年患者单药皮下注射阿扎胞苷100 mg/m²/天、为期5天的方案的耐受性和疗效,其中14例患者的BM原始细胞计数>30%。总缓解率为47%。完全缓解、部分缓解和血液学改善分别在20%、13%和13%的患者中实现。整个队列的中位总生存期为355天,缓解者为532天。达到最佳缓解的中位时间为95天,中位治疗持续时间为198天(范围=13-724天)。3-4级血液学毒性主要包括发热性中性粒细胞减少(40%)和血小板减少(20%)。发热性中性粒细胞减少是住院的最常见原因。非血液学毒性包括注射部位皮肤反应和疲劳(1-2级),发生在73%(n=11)的患者中。研究期间未发生与治疗相关的死亡。除4例患者外,所有患者治疗的剂量和方案均保持不变。本研究结果表明,每28天给予皮下注射阿扎胞苷100 mg/m²/天、为期5天,对于老年AML患者是一种可行、耐受性良好且有效的标准诱导化疗替代方案。