Flavopiridol administered as a 24-hour continuous infusion in chronic lymphocytic leukemia lacks clinical activity
Flavopiridol administered as a 24-hour continuous infusion in chronic lymphocytic leukemia lacks clinical activity
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DOI：
10.1016/j.leukres.2005.03.010
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发表时间：
2005-11-01
影响因子：
2.7
通讯作者：
Grever, MR
中科院分区：
文献类型：
--
作者：
Flinn, IW;Byrd, JC;Grever, MR
简介：黄吡醇的研究表明，该药物在慢性淋巴细胞白血病（CLL）中具有体外活性，并促进细胞凋亡，而不依赖于p53功能或先前的氟达拉滨暴露。基于这些临床前数据，进行了24小时黄匹吡醇的I/II期研究。患者和方法：既往治疗过的CLL患者被纳入两个顺序进行的队列，共13例患者。第一组患者每2周接受黄匹吡醇（80 mg/m(2)） 24小时连续输注[24 h CI]。第二组患者在第1周接受黄匹吡醇（80 mg/m(2)作为24小时CI）治疗，然后在无症状的情况下，每2周剂量递增20 mg/m(2)至最大剂量140 mg/m(2)。患者接受了多达12剂的治疗。结果：每个队列纳入了13例氟达拉滨难治性或不耐受性CLL患者。在每个队列中，患者平均接受5次治疗，只有2名患者完成了全部12个疗程的治疗。没有记录到部分或完全的回答。大多数患者的毒性是可控的，包括贫血、血小板减少症、感染、腹泻和疲劳。结论：黄匹吡醇连续输注24小时对复发性氟达拉滨难治性CLL无临床活性。(c) 2005年Elsevier Ltd出版
Introduction: Studies with flavopiridol have demonstrated that this agent has in vitro activity in chronic lymphocytic leukemia (CLL) and promotes apoptosis independent of p53 function or prior fludarabine, exposure. Based upon this pre-clinical data, a phase I/II study of 24 h flavopiridol was performed.Patients and methods: Patients with previously treated CLL patients were enrolled on two sequentially performed cohorts of 13 patients. Patients in the first cohort received flavopiridol (80 mg/m(2) as a 24-h continuous infusion [24 h CI]) every 2 weeks. Patients in the second cohort received flavopiridol (80 mg/m(2) as a 24h CI) for week 1 and then were dose escalated by 20 mg/m(2) every 2 weeks to a maximal dose of 140 mg/m(2) in the absence of symptoms. Patients received up to 12 doses of therapy.Results: Thirteen patients with fludarabine-refractory or intolerant CLL enrolled in each cohort. Patients received a median of five treatments in each cohort with only two patients completing all 12 courses of therapy. There were no partial or complete responses noted. Toxicity was manageable in most patients and included anemia, thrombocytopenia, infections, diarrhea, and fatigue. Conclusions: Flavopiridol as a 24-h continuous infusion has no clinical activity in relapsed, fludarabine-refractory CLL. (c) 2005 Published by Elsevier Ltd.