Ganesan T S, Barnett M J, Amos R J, Piall E M, Aherne G W, Man A, Lister T A
Hematol Oncol. 1987 Jan-Mar;5(1):65-9. doi: 10.1002/hon.2900050108.
A Phase II study of high dose cytosine arabinoside (ara-C) with different schedules in patients with recurrent acute myelogenous leukaemia (AML) and myeloid blast crisis of chronic myeloid leukaemia has been conducted at St. Bartholomew's Hospital. Ara-C was infused continuously for seven days at a dose of 100-200 mgs/m2 daily from day 1 with 1-2 g/m2 (3 h infusions) twice daily from day 2 for six days. Nineteen patients with acute myelogenous leukaemia and four patients with myeloid blast crisis of chronic myeloid leukaemia (CML) were treated. Complete remission was achieved in 4/19 patients with AML and in a further four patients an antileukaemic effect was observed. There were eight early deaths and three patients failed to show any response to therapy. All four patients with myeloid blast crisis of CML failed to respond to the treatment. Toxicity was considerable with gastro-intestinal and hepatotoxicity being the most serious problems. Pharmacokinetic studies revealed that mean basal levels achieved with continuous infusion prior to high-dose ara-C were 10(2) ng/ml and peak levels were of the order of 10(4) ng/ml. The considerable toxicity of the regimen, without clinical advantage over less intensive programmes, resulted in its termination.
圣巴塞洛缪医院开展了一项针对复发急性髓性白血病（AML）和慢性髓性白血病髓系原始细胞危象患者的Ⅱ期研究，采用不同给药方案给予高剂量阿糖胞苷（ara-C）。从第1天起，阿糖胞苷以每日100 - 200毫克/平方米的剂量持续输注7天，从第2天起，每日两次，每次1 - 2克/平方米（3小时输注），共6天。治疗了19例急性髓性白血病患者和4例慢性髓性白血病（CML）髓系原始细胞危象患者。19例AML患者中有4例实现完全缓解，另有4例观察到抗白血病效应。有8例早期死亡，3例患者对治疗无反应。所有4例CML髓系原始细胞危象患者对治疗均无反应。毒性相当大，胃肠道和肝毒性是最严重的问题。药代动力学研究表明，在高剂量阿糖胞苷之前持续输注所达到的平均基础水平为10²纳克/毫升，峰值水平约为10⁴纳克/毫升。该方案毒性相当大，且相对于强度较低的方案无临床优势，因此试验终止。
