二期试验口服氨喋呤为成人和儿童难治性急性白血病。
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科尔PD, Drachtman RA,史密斯AK,美食,拉尔森RA,霍金斯DS, Holcenberg J,凯利K,卡门英航
二期试验口服氨喋呤为成人和儿童难治性急性白血病。
癌症研究杂志2005年11月15日,11 (22):8089 - 96。
- PubMed ID
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16299240 (在PubMed]
- 文摘
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目的:确定每周的antileukemic活动在难治性急性白血病患者口服氨喋呤;氨喋呤的药效学性质描述;并对比氨喋呤和甲氨蝶呤的胞内代谢患者体外。实验设计:46名患者参加三个阶层:儿童急性淋巴细胞白血病(ALL),成人患者,急性髓系白血病(AML)患者。氨喋呤被周刊》在两个剂量的2毫克/ m(2), 12个小时。有限的抽样药代动力学分析是在治疗的第一个星期完成的。(3)H氨喋呤和积累[(3)H]研究了甲氨蝶呤的白血病细胞体外。结果:22个孩子所有6 (27%;95%置信区间,8 - 47%)有临床意义上的反应。这些与AML和11只有两个成年人都有反应会议协议定义,虽然外围爆炸倾向于减少在所有组与治疗。 Mucosal toxicity was minimal, even with limited use of leucovorin rescue. Complete bioavailability of aminopterin was confirmed, with a mean area under the curve of 0.52 +/- 0.03 micromol hour/L after oral dosing. No relationship between aminopterin pharmacokinetics and response was seen. In vitro, aminopterin showed more consistent metabolism by leukemic blasts to polyglutamates than methotrexate. Lineage-specific differences in the pattern of intracellular antifolylpolyglutamates were observed. CONCLUSIONS: Weekly oral aminopterin has significant activity among children with refractory ALL. With greater cellular accumulation and metabolism, more reliable bioavailability than methotrexate, and tolerable toxicity at this dose and schedule, aminopterin deserves further study as a potent alternative to methotrexate.
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