Division of Hematologic Malignancies, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland 21231-1000, USA.
Haematologica. 2012 Nov;97(11):1736-42. doi: 10.3324/haematol.2012.062539. Epub 2012 Jun 24.
Flavopiridol is a protein-bound, cytotoxic, cyclin dependent kinase inhibitor. A phase II trial of flavopiridol followed by ara-C and mitoxantrone with flavopiridol given by 1-h bolus for adults with newly-diagnosed, poor-risk acute myelogenous leukemia yielded 67% complete remission with median disease-free survival of 13.6 months.
We compared bolus flavopiridol (50 mg/m(2)/day, Arm A) versus 'hybrid' flavopiridol (30 mg/m(2) over 30 min followed by 40 mg/m(2) over 4 h, Arm B) followed by ara-C and mitoxantrone in 78 patients (39 per arm) with newly diagnosed, poor-risk acute myelogenous leukemia. To mitigate imbalance, patients were stratified by presence or absence of secondary leukemia and therapy for antecedent disorder.
Death at or before Day 60 occurred in 8% of patients per arm. Complete remission plus complete remission with incomplete recovery was 68% (Arm A, 62%; Arm B, 74%) overall, and 65% or over in both arms for patients with secondary leukemia and leukemia with adverse genetics. In Arm A 91% and in Arm B 86% of patients received chemotherapy and/or allogeneic transplantation in complete remission. Median overall survival for all remission patients has not been reached for either arm, with median disease free survival of 13.6 months for Arm A and of 12.0 months for Arm B.
Both flavopiridol schedules produce comparably encouraging results in adults with poor-risk acute myelogenous leukemia. Given the greater ease of bolus administration, we are conducting a randomized phase II study of bolus flavopiridol followed by ara-c and mitoxantrone versus conventional induction therapy for patients aged 70 years and under with intermediate or poor-risk acute myelogenous leukemia. This study is registered at www.clinicaltrials.gov as #NCT 00407966.
Flavopiridol 是一种蛋白结合的细胞毒性细胞周期蛋白依赖性激酶抑制剂。一项在新诊断的高危急性髓系白血病患者中进行的 flavopiridol 联合阿糖胞苷和米托蒽醌的 II 期临床试验，使用 1 小时推注的 flavopiridol 方案，获得了 67%的完全缓解率，中位无疾病生存时间为 13.6 个月。
我们比较了新诊断的高危急性髓系白血病患者 78 例（每组 39 例）中，推注 flavopiridol（50mg/m2/天，A 组）与“混合”flavopiridol（30mg/m2 输注 30 分钟，随后 40mg/m2 输注 4 小时，B 组），随后给予阿糖胞苷和米托蒽醌。为了减轻不平衡，根据是否存在继发性白血病和先前疾病的治疗情况对患者进行分层。
每组各有 8%的患者在第 60 天或之前死亡。完全缓解加上不完全恢复的完全缓解率为 68%（A 组 62%；B 组 74%），在有继发性白血病和遗传不良的白血病患者中，两个臂的缓解率均为 65%或更高。在 A 组，91%的患者和 B 组，86%的患者在完全缓解时接受了化疗和/或同种异体移植。两个臂的所有缓解患者的中位总生存时间均未达到，A 组无疾病生存时间为 13.6 个月，B 组为 12.0 个月。
两种 flavopiridol 方案在高危急性髓系白血病成人患者中均产生了令人鼓舞的结果。鉴于推注给药更为方便，我们正在进行一项针对年龄在 70 岁以下的中危或高危急性髓系白血病患者的随机 II 期研究，比较推注 flavopiridol 联合阿糖胞苷和米托蒽醌与常规诱导治疗的疗效。该研究在 www.clinicaltrials.gov 上注册，编号为#NCT 00407966。
