A pilot trial of the mTOR (mammalian target of rapamycin) inhibitor RAD001 in patients with advanced B-CLL
A pilot trial of the mTOR (mammalian target of rapamycin) inhibitor RAD001 in patients with advanced B-CLL
复制标题
DOI：
10.1007/s00277-008-0582-9
复制
发表时间：
2009-03-01
影响因子：
3.5
通讯作者：
Peschel, Christian
中科院分区：
文献类型：
--
作者：
Decker, Thomas;Sandherr, Michael;Peschel, Christian
虽然b细胞慢性淋巴细胞白血病（CLL）是可以治疗的，但它仍然是一种无法治愈的疾病，大多数患者不可避免地会复发。对于那些需要治疗的患者，存在许多治疗选择，包括单克隆抗体和干细胞移植，但在疾病过程中缓解往往持续时间较短。靶向细胞周期最近被认为是一种有吸引力的治疗实体和血液恶性肿瘤的方法，并且B-CLL的增殖性质越来越被接受。在此，我们报告了一项II期试点试验的数据，该试验采用口服雷帕霉素（mTOR）抑制剂RAD001 5mg /d治疗晚期B-CLL患者，这些患者在至少两线治疗后病情进展。在治疗了7名患者后，该试验因毒性问题而停止，尽管观察到一定程度的活性（1名患者部分缓解，3名患者病情稳定）。有趣的是，在有反应的患者中，cyclin E的表达有所下降。在B-CLL中，RAD001进一步抑制mTOR的策略应侧重于不同的治疗方案、充分的抗感染预防或与细胞毒性药物联合使用。
Although B-cell chronic lymphocytic leukemia (CLL) is treatable, it remains an incurable disease and most patients inevitably suffer relapse. Many therapeutic options exist for those requiring therapy, including monoclonal antibodies and stem cell transplantation, but remissions tend to last shorter in the course of the disease. Targeting the cell cycle has recently been realized to be an attractive therapeutic approach in solid and hematological malignancies, and the proliferative nature of B-CLL is increasingly accepted. Here, we report data on a phase II pilot trial with the oral mammalian target of rapamycin (mTOR) inhibitor RAD001 5 mg/daily in patients with advanced B-CLL who had progressive disease after at least two lines of treatment. After treatment of seven patients, this trial was stopped because of toxicity concerns, although some degree of activity was observed (one partial remission, three patients with stable disease). Interestingly, cyclin E expression decreased in responding patients. Further strategies of mTOR inhibition by RAD001 in B-CLL should focus on different treatment schedules, adequate anti-infectious prophylaxis, or combinations with cytotoxic drugs.