Randomized Trial of Intermediate-dose Cytarabine in Induction and Consolidation Therapy in Adults with Acute Myeloid Leukemia

• Published in: Clinical cancer research Vol. 26; no. 13; pp. 3154 - 3161
• Main Authors: Wei, Hui, Wang, Ying, Gale, Robert Peter, Lin, Dong, Zhou, Chunlin, Liu, Bingcheng, Qiu, Shaowei, Gu, Runxia, Li, Yan, Zhao, Xingli, Wei, Shuning, Gong, Benfa, Liu, Kaiqi, Gong, Xiaoyuan, Liu, Yuntao, Zhang, Guangji, Song, Zhen, Wang, Yang, Li, Wei, Mi, Yingchang, Wang, Jianxiang
• Format: Journal Article
• Language: English
• Published: United States 01.07.2020
• Subjects: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Consolidation Chemotherapy; Cytarabine; Daunorubicin; Humans; Leukemia, Myeloid, Acute - drug therapy; Middle Aged; Remission Induction; Young Adult
• ISSN: 1078-0432; 1557-3265; 1557-3265
• DOI: 10.1158/1078-0432.CCR-19-3433

Cytarabine, 100-200 mg/mE+2/day, is commonly used in induction therapy of acute myelogenous leukemia (AML). Whether a higher dose of cytarabine would be more effective is unknown. Also, there is controversy whether high-dose cytarabine is better than an intermediate-dose combined with other drugs for post-remission therapy. In this open-label, randomized controlled, parallel group study, roles of intermediate-dose cytarabine were investigated. Subjects with AML age 15-55 years were randomized to receive daunorubicin, omacetaxine mepesuccinate, and conventional- or intermediate-dose cytarabine. Subjects achieving complete remission were randomized to receive 3 courses of high-dose cytarabine or 2 courses of intermediate-dose cytarabine with daunorubicin in the 1 and mitoxantrone in the 2 course. The primary endpoint was disease-free survival (DFS). 591 subjects were randomized to intermediate- ( = 295) or conventional-dose ( = 296) cytarabine group. Three-year DFSs were 67% [95% confidence interval (CI), 61-73] in the intermediate-dose cohort compared with 54% (95% CI, 48-61) in the conventional-dose cohort [Hazard Ratio (HR), 0.67; 95%CI, 0.51-0.89; = 0.005). Three-year survivals were 68% (95%CI, 63-74) and 59% (95%CI, 53-65; HR, 0.720; 95%CI, 0.56-0.94; = 0.014). Two courses of intermediate-dose cytarabine with daunorubicin or mitoxantrone resulted in similar DFS and survival as three courses of high-dose cytarabine when used for post-remission therapy. Induction therapy with intermediate-dose cytarabine with daunorubicin and omacetaxine mepesuccinate increases DFS and survival in persons with AML ages 15-55 years compared with conventional-dose cytarabine. .