a Servicio de Farmacia, Área del Medicamento , Hospital Universitari i Politècnic La Fe , Valencia , Spain.
b Servicio de Hematología y Hemoterapia , Hospital Universitari i Politècnic La Fe , Valencia , Spain.
Expert Rev Clin Pharmacol. 2019 Mar;12(3):197-218. doi: 10.1080/17512433.2019.1573668. Epub 2019 Feb 6.
Induction chemotherapy based on anthracyclines and cytarabine (Ara-C) combination remains the standard of care for acute myeloid leukemia (AML) patients who are considered candidate for intensive and curative approaches. However, the toxicity of this regimen is high, with disappointing clinical outcomes among the so-called poor-prognosis AML subsets, which generally refer to patients with adverse cytogenetic risk, secondary AML including therapy-related AML, poor-prognosis mutations, especially FLT3-ITD, and relapse/refractory AML. Areas covered: To the best of our knowledge, the role and efficacy of 7 + 3 schedules containing daunorubicin (DNR) and Ara-C for certain types of poor-prognosis AML has not been systematically assessed. A critical approach to the role of DNR and Ara-C induction could be relevant to establish which patients should be enrolled in clinical trials using novel therapies. Expert commentary: In this regard, a recent randomized clinical trial (RCT) showed improved results in older patients with sAML or high-risk cytogenetics who received CPX-351 compared with standard 7 + 3 combination. We perform a systematic literature review to analyze the clinical outcomes reported with DNR plus Ara-C regimens in adult patients with poor-prognosis AML, the use of liposomal formulations of DNR and Ara-C and the RCTs which compared standard 7 + 3 with the addition of a third drug.
基于蒽环类药物和阿糖胞苷（Ara-C）联合的诱导化疗仍然是适合强化和治愈方法的急性髓系白血病（AML）患者的标准治疗方法。然而，这种方案的毒性很高，所谓的预后不良 AML 亚组的临床结果令人失望，这些亚组通常指具有不良细胞遗传学风险、继发性 AML 包括治疗相关 AML、预后不良突变的患者，特别是 FLT3-ITD，以及复发/难治性 AML。
据我们所知，含有柔红霉素（DNR）和 Ara-C 的 7+3 方案在某些类型的预后不良 AML 中的作用和疗效尚未得到系统评估。对 DNR 和 Ara-C 诱导作用的批判性方法可能与确定应将哪些患者纳入使用新型疗法的临床试验有关。
在这方面，最近的一项随机临床试验（RCT）表明，与标准的 7+3 联合方案相比，接受 CPX-351 的老年 sAML 或高危细胞遗传学患者的结果得到改善。我们进行了系统的文献回顾，以分析在预后不良的 AML 成年患者中使用 DNR 加 Ara-C 方案报告的临床结果，使用柔红霉素和 Ara-C 的脂质体制剂，以及将标准的 7+3 与第三种药物联合使用的 RCT。
