Tamibarotene as maintenance therapy for acute promyelocytic leukemia: results from a randomized controlled trial.

Abstract

PURPOSE:

The introduction of all-trans-retinoic acid (ATRA) has significantly improved outcomes for acute promyelocytic leukemia (APL), although a subset of patients still suffer relapse. The purpose of this study was to evaluate the role of maintenance therapy with the synthetic retinoid tamibarotene in APL.

PATIENTS AND METHODS:

Patients with newly diagnosed APL in molecular remission at the end of consolidation therapy were randomly assigned to receive ATRA or tamibarotene, both orally, for 14 days every 3 months for up to 2 years.

RESULTS:

A total of 347 patients were enrolled. Of the 344 eligible patients, 319 (93%) achieved complete remission. After completing three courses of consolidation therapy, 269 patients underwent maintenance random assignment. The relapse-free survival (RFS) rate at 4 years was 84% for the ATRA arm and 91% for the tamibarotene arm (hazard ratio [HR], 0.54; 95% CI, 0.26 to 1.13). When the analysis was restricted to 52 high-risk patients with an initial WBC count ≥ 10.0 × 10(9)/L, the intergroup difference was statistically significant, with 4-year RFS rates of 58% for the ATRA arm and 87% for the tamibarotene arm (HR, 0.26; 95% CI, 0.07 to 0.95). For patients with non-high-risk disease, the HR was 0.82 (95% CI, 0.32 to 2.01). The test for interaction between treatment effects and these subgroups resulted in P = .075. Both treatments were generally well tolerated.

CONCLUSION:

In this trial, no difference was detected between ATRA and tamibarotene for maintenance therapy. In an exploratory analysis, there was a suggestion of improved efficacy of tamibarotene in high-risk patients, but this requires further study.

• Authors: Katsuji Shinagawa, Masamitsu Yanada, Toru Sakura, Yasunori Ueda, Masashi Sawa, Junichi Miyatake, Nobuaki Dobashi, Minoru Kojima, Yoshihiro Hatta, Nobuhiko Emi, Shigehisa Tamaki, Hiroshi Gomyo, Etsuko Yamazaki, Katsumichi Fujimaki, Norio Asou, Keitaro Matsuo, Shigeki Ohtake, Yasushi Miyazaki, Kazunori Ohnishi, Yukio Kobayashi, Tomoki Naoe
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 33 Pg. 3729-35 (Nov 20 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 25245439 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Comment)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• Antineoplastic Agents
• Arsenicals
• Oxides
• Arsenic Trioxide

Topics

• Antineoplastic Agents (adverse effects)
• Arsenic Trioxide
• Arsenicals (adverse effects)
• Electrocardiography (drug effects)
• Female
• Humans
• Male
• Oxides (adverse effects)