Interim comparison of a continuous infusion versus a short daily infusion of cytarabine given in combination with cladribine for pediatric acute myeloid leukemia
Interim comparison of a continuous infusion versus a short daily infusion of cytarabine given in combination with cladribine for pediatric acute myeloid leukemia
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DOI：
10.1200/jco.2002.10.006
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发表时间：
2002-10-15
影响因子：
45.3
通讯作者：
Ribeiro, RC
中科院分区：
文献类型：
--
作者：
Crews, KR;Gandhi, V;Ribeiro, RC
目的：确定急性髓系白血病 (AML) 儿科患者输注阿糖胞苷 (ara-C) 与克拉屈滨 (2-CdA) 的最佳方案，并比较两种方案对白血病细胞中 ara-C 三磷酸 (ara-CTP) 药代动力学的影响。 患者和方法：49 名新诊断的原发性 AML 儿科患者接受了为期 5 天的疗程ara-C 500 mg/m(2)/d 和 2-CdA 9 mg/m(2)/d。他们被随机分配接受 ara-C 每日 2 小时输注（A 组）或连续输注（E 组）。在第 1 天和第 2 天研究细胞药代动力学。然后，所有患者均接受两个疗程的柔红霉素、ara-C 和依托泊苷 (DAV) 诱导缓解化疗。结果：A 组中 32% 的患者（22 人中的 7 人）和 B 组中 63%（27 人中的 17 人）在 ara-C 和 2-CdA 治疗后进入完全缓解 (P = 0.045)。 36 名患者中有 20 名同时服用 2-CdA 增加了 ara-CTP 的细胞内浓度，尽管我们发现治疗组之间的这种效果没有统计学上的显着差异 (P =.63)。两个治疗组之间的毒性发生率没有显着差异 (P =.53)。两个疗程的 DAV 后，A 组的完全缓解率为 91%，B 组的完全缓解率为 96% (P =.58)。结论：当 2-CdA 与 ara-C 联合给药时，ara-CTP 的细胞内积累增加，但未观察到这种效应存在与疗程相关的差异。 2-CdA 和 ara-C 的组合似乎是治疗儿童 AML 的有效疗法。
Purpose : To identify the optimal schedule for infusion of cytarabine (ara-C) given with cladribine (2-CdA) to pediatric patients with acute myeloid leukemia (AML), and to compare the effects of the two schedules on the pharmccokinetics of ara-C triphosphate (ara-CTP) in leukemic cells.Patients and Methods: Forty-nine pediatric patients with newly diagnosed primary AML received a 5-day course of ara-C 500 mg/m(2)/d and 2-CdA 9 mg/m(2)/d. They were randomly assigned to receive ara-C as either a 2-hour daily infusion (arm A) or a continuous infusion (arm E). Cellular pharmacokinetics were studied on days 1 and 2. All patients then received two courses of remission induction chemotherapy with daunorubicin, ara-C, and etoposide (DAV).Results: Thirty-two percent of patients (seven of 22) in arm A and 63% (17 of 27) in arm B entered complete remission (P =.045) after ara-C and 2-CdA therapy. Coadministration of 2-CdA increased the intracellular concentration of ara-CTP in 20 of 36 patients, although we found no statistically significant difference between the treatment arms in this effect (P =.63). The incidence of toxicity did not differ significantly between the two treatment arms (P =.53). After two courses of DAV, the rate of complete remission was 91% in arm A and 96% in arm B (P =.58).Conclusion: Intracellular accumulation of ara-CTP is increased when 2-CdA is given with ara-C, but no schedule-dependent differences in this effect were seen. The combination of 2-CdA and ara-C seems to be effective therapy for pediatric AML.