Faderl Stefan, Ferrajoli Alessandra, Wierda William, Huang Xuelin, Verstovsek Srdan, Ravandi Farhad, Estrov Zeev, Borthakur Gautam, Kwari Monica, Kantarjian Hagop M
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2008 Oct 15;113(8):2090-6. doi: 10.1002/cncr.23816.
Outcome of patients with relapsed acute myeloid leukemia (AML) remains unsatisfactory. Clofarabine is a nucleoside analog with activity in adult AML. Combinations with cytarabine in AML are feasible and effective. Idarubicin is another active AML drug, which has not yet been tested with clofarabine.
The authors therefore designed a phase I study of clofarabine +/- cytarabine, plus idarubicin. Patients with primary refractory or first-relapse AML were assigned to either clofarabine plus idarubicin (CI) if previously exposed to cytarabine with a response lasting <12 months, or clofarabine and idarubicin plus cytarabine (CIA) for responses > or = 12 months, or if never exposed to cytarabine. A standard "3 + 3" phase 1 design was followed to define maximum tolerated dose (MTD). Forty-four patients were treated (23 CI; 21 CIA).
Dose-limiting toxicities were hyperbilirubinemia and hepatic transaminase elevations for CI-treated patients in addition to mucositis and diarrhea for CIA-treated patients. MTD for CI was clofarabine 22.5 mg/m(2) intravenously daily x 5 and idarubicin 10 mg/m(2) intravenously daily x 3. MTD for CIA was clofarabine 22.5 mg/m(2) intravenously x 5, idarubicin 6 mg/m(2) intravenously x 3, and cytarabine 0.75 g/m(2) intravenously x 5 days.
A phase 2 randomized trial is in process to compare activity between treatment arms.
复发急性髓系白血病（AML）患者的预后仍不尽人意。氯法拉滨是一种对成人AML有活性的核苷类似物。与阿糖胞苷联合用于AML是可行且有效的。伊达比星是另一种对AML有活性的药物，但尚未与氯法拉滨联合进行过试验。
因此，作者设计了一项关于氯法拉滨±阿糖胞苷加伊达比星的I期研究。原发性难治或首次复发的AML患者，如果之前使用阿糖胞苷治疗且缓解持续时间<12个月，则分配至氯法拉滨加伊达比星（CI）组；如果缓解持续时间≥12个月，或者从未接触过阿糖胞苷，则分配至氯法拉滨、伊达比星加阿糖胞苷（CIA）组。采用标准的“3+3”I期设计来确定最大耐受剂量（MTD）。44例患者接受了治疗（23例CI组；21例CIA组）。
CI组治疗患者的剂量限制性毒性为高胆红素血症和肝转氨酶升高，CIA组治疗患者的剂量限制性毒性为黏膜炎和腹泻。CI组的MTD为氯法拉滨22.5mg/m²静脉滴注每日1次×5天，伊达比星10mg/m²静脉滴注每日1次×3天。CIA组的MTD为氯法拉滨22.5mg/m²静脉滴注×5天，伊达比星6mg/m²静脉滴注×3天，阿糖胞苷0.75g/m²静脉滴注×5天。
一项比较各治疗组活性的II期随机试验正在进行中。
