Arnaud Pigneux and Mathieu Sauvezie, Centre Hospitalier Universitaire (CHU) Bordeaux, Université Bordeaux, Institut National de la Santé et de la Recherche Médicale (INSERM) 1035, Bordeaux; Marie C. Béné and Jean-Luc Harousseau, Hôpital Hôtel Dieu, Nantes; Philippe Guardiola, Mathilde Hunault, and Norbert Ifrah, CHU Angers, UMR INSERM U892/CNRS 6299; Jean-Francois Hamel, Université Nantes Angers Le Mans, CHU Angers, Angers; Christian Recher, CHU de Toulouse, Université de Toulouse III, Toulouse; Olivier Tournilhac, CHU Clermont Ferrand, Clermont Ferrand; Francis Witz, CHU Nancy, Nancy; Christian Berthou, Hôpital Augustin Morvan, Brest; Martine Escoffre-Barbe, Hôpital Pontchaillou, Rennes; Denis Guyotat, Institut de Cancérologie de la Loire, Saint Etienne; Nathalie Fegueux, Hôpital Lapeyronie, Montpellier; Chantal Himberlin, CHU Reims, Reims; Martine Delain, Hôpital Bretonneau, Tours; Bruno Lioure, CHU Hautepierre, Strasbourg; Eric Jourdan, Hôpital Caremeau, Nîmes; Frederic Bauduer, Centre Hospitalier Cote Basque, Bayonne; Francois Dreyfus, Hôpital Cochin, Paris; and Jean-Yves Cahn and Jean-Jacques Sotto, Hôpital Michallon, Grenoble, France.
J Clin Oncol. 2017 Feb;35(4):387-393. doi: 10.1200/JCO.2016.67.6213. Epub 2016 Oct 24.
Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study. Induction therapy included idarubicin 8 mg/m on days 1 to 5, cytarabine 100 mg/m on days 1 to 7, and lomustine 200 mg/m on day 1. Patients in complete remission or partial remission received six reinduction courses, alternating idarubicin 8 mg/m on day 1, cytarabine 100 mg/m on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were randomly assigned to receive norethandrolone 10 or 20 mg/day, according to body weight, or no norethandrolone for a 2-year maintenance therapy regimen. The primary end point was disease-free survival by intention to treat. Secondary end points were event-free survival, overall survival, and safety. This trial was registered at www.ClinicalTrials.gov identifier NCT00700544. Results Random assignment allotted 165 patients to each arm; arm A received norethandrolone, and arm B did not receive norethandrolone. Complete remission or partial remission was achieved in 247 patients (76%). The Schoenfeld time-dependent model showed that norethandrolone significantly improved survival for patients still in remission at 1 year after induction. In arms A and B, respectively, 5-year disease-free survival was 31.2% and 16.2%, event-free survival was 21.5% and 12.9%, and overall survival was 26.3% and 17.2%. Norethandrolone improved outcomes irrelevant to all prognosis factors. Only patients with baseline leukocytes > 30 × 10/L did not benefit from norethandrolone. Conclusion This study demonstrates that maintenance therapy with norethandrolone significantly improves survival in elderly patients with AML without increasing toxicity.
老年急性髓系白血病（AML）患者预后较差，创新的维持治疗可能改善其预后。雄激素被用于治疗再生障碍性贫血，已被报道可阻断 AML 细胞的增殖并启动其分化。我们报告了一项多中心、III 期、随机、开放标签试验的结果，该试验探讨了在 60 岁及以上患者中添加雄激素进行维持治疗的益处。
共有 330 例初治或继发于化疗或放疗的 AML 患者入组本研究。诱导治疗包括阿糖胞苷 100mg/m2 第 1-7 天，依托泊苷 8mg/m2 第 1-5 天，洛莫司汀 200mg/m2 第 1 天。完全缓解或部分缓解的患者接受 6 个再诱导疗程，依托泊苷 8mg/m2 第 1 天，阿糖胞苷 100mg/m2 第 1-5 天，甲氨蝶呤和巯嘌呤方案交替。患者根据体重随机分配接受去氢甲睾酮 10 或 20mg/天，或不接受去氢甲睾酮进行 2 年维持治疗方案。主要终点为意向治疗的无病生存。次要终点为无事件生存、总生存和安全性。本研究在 www.ClinicalTrials.gov 注册号为 NCT00700544。
随机分配 165 例患者至各治疗组；组 A 接受去氢甲睾酮，组 B 不接受去氢甲睾酮。247 例（76%）患者达到完全缓解或部分缓解。Schoenfeld 时依模型显示，诱导后 1 年仍缓解的患者，去氢甲睾酮可显著改善生存。在组 A 和组 B 中，5 年无病生存率分别为 31.2%和 16.2%，无事件生存率分别为 21.5%和 12.9%，总生存率分别为 26.3%和 17.2%。去氢甲睾酮改善了与所有预后因素无关的结果。仅基线白细胞计数>30×10/L 的患者未从去氢甲睾酮治疗中获益。
本研究表明，去氢甲睾酮维持治疗可显著改善老年 AML 患者的生存，且不增加毒性。
