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

Abstract

PURPOSE:

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.

PATIENTS AND METHODS:

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 1st and mitoxantrone in the 2nd course. The primary endpoint was disease-free survival (DFS).

RESULTS:

591 subjects were randomized to intermediate- (N = 295) or conventional-dose (N = 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; P = 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; P = 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.

CONCLUSIONS:

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.See related commentary by Watts and Bradley, p. 3073.

• Authors: Hui Wei, Ying Wang, Robert Peter Gale, Dong Lin, Chunlin Zhou, Bingcheng Liu, Shaowei Qiu, Runxia Gu, Yan Li, Xingli Zhao, Shuning Wei, Benfa Gong, Kaiqi Liu, Xiaoyuan Gong, Yuntao Liu, Guangji Zhang, Zhen Song, Yang Wang, Wei Li, Yingchang Mi, Jianxiang Wang
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 13 Pg. 3154-3161 (07 01 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 32029439 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Comment)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Cytarabine
• Daunorubicin

Topics

• Adolescent
• Adult
• Antineoplastic Combined Chemotherapy Protocols (adverse effects)
• Consolidation Chemotherapy
• Cytarabine
• Daunorubicin
• Humans
• Leukemia, Myeloid, Acute (drug therapy)
• Middle Aged
• Remission Induction
• Young Adult