Dipartimento di Biomedicina e Prevenzione, Università Tor Vergata, Rome, Italy.
N Engl J Med. 2013 Jul 11;369(2):111-21. doi: 10.1056/NEJMoa1300874.
All-trans retinoic acid (ATRA) with chemotherapy is the standard of care for acute promyelocytic leukemia (APL), resulting in cure rates exceeding 80%. Pilot studies of treatment with arsenic trioxide with or without ATRA have shown high efficacy and reduced hematologic toxicity.
We conducted a phase 3, multicenter trial comparing ATRA plus chemotherapy with ATRA plus arsenic trioxide in patients with APL classified as low-to-intermediate risk (white-cell count, ≤10×10(9) per liter). Patients were randomly assigned to receive either ATRA plus arsenic trioxide for induction and consolidation therapy or standard ATRA-idarubicin induction therapy followed by three cycles of consolidation therapy with ATRA plus chemotherapy and maintenance therapy with low-dose chemotherapy and ATRA. The study was designed as a noninferiority trial to show that the difference between the rates of event-free survival at 2 years in the two groups was not greater than 5%.
Complete remission was achieved in all 77 patients in the ATRA-arsenic trioxide group who could be evaluated (100%) and in 75 of 79 patients in the ATRA-chemotherapy group (95%) (P=0.12). The median follow-up was 34.4 months. Two-year event-free survival rates were 97% in the ATRA-arsenic trioxide group and 86% in the ATRA-chemotherapy group (95% confidence interval for the difference, 2 to 22 percentage points; P<0.001 for noninferiority and P=0.02 for superiority of ATRA-arsenic trioxide). Overall survival was also better with ATRA-arsenic trioxide (P=0.02). As compared with ATRA-chemotherapy, ATRA-arsenic trioxide was associated with less hematologic toxicity and fewer infections but with more hepatic toxicity.
ATRA plus arsenic trioxide is at least not inferior and may be superior to ATRA plus chemotherapy in the treatment of patients with low-to-intermediate-risk APL. (Funded by Associazione Italiana contro le Leucemie and others; ClinicalTrials.gov number, NCT00482833.).
全反式维甲酸（ATRA）联合化疗是急性早幼粒细胞白血病（APL）的标准治疗方法，其治愈率超过 80%。三氧化二砷联合或不联合 ATRA 的治疗的初步研究表明，其具有高疗效和降低血液学毒性的特点。
我们开展了一项 3 期、多中心试验，比较了低-中危（白细胞计数≤10×10（9）/升）APL 患者接受 ATRA 联合化疗与 ATRA 联合三氧化二砷治疗的效果。患者随机分为接受 ATRA 联合三氧化二砷诱导和巩固治疗或标准 ATRA-伊达比星诱导治疗，随后接受 3 个周期的 ATRA 联合化疗巩固治疗和低剂量化疗及 ATRA 维持治疗。该研究设计为非劣效性试验，旨在表明两组患者在 2 年无事件生存的差异不超过 5%。
可评估的 77 例 ATRA-三氧化二砷组患者全部达到完全缓解（100%），79 例 ATRA-化疗组患者中有 75 例达到完全缓解（95%）（P=0.12）。中位随访时间为 34.4 个月。ATRA-三氧化二砷组和 ATRA-化疗组的 2 年无事件生存率分别为 97%和 86%（差异的 95%置信区间为 2 至 22 个百分点；ATRA-三氧化二砷非劣效性检验 P<0.001，优效性检验 P=0.02）。ATRA-三氧化二砷组的总生存率也更好（P=0.02）。与 ATRA-化疗相比，ATRA-三氧化二砷治疗与较少的血液学毒性和感染相关，但与更多的肝毒性相关。
ATRA 联合三氧化二砷在治疗低-中危 APL 患者方面至少不劣效，且可能优于 ATRA 联合化疗。（由意大利白血病协会等资助；ClinicalTrials.gov 编号，NCT00482833）。
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