低剂量全反式维甲酸治疗急性早幼粒细胞白血病的疗效

PHARMACOKINETICS AND EFFICACY OF LOW DOSE ALL TRANS RETINOIC ACID IN THE TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA

为了评价低剂量全反式维甲酸（ＡＴＲＡ）治疗急性早幼粒细胞白血病（ＡＰＬ）的临床效果，分别比较了正常个体单次口服１５ｍｇ／ｍ２和４５ｍｇ／ｍ２ＡＴＲＡ的药代动力学。结果显示：口服低剂量的最大峰浓度（Ｃｍａｘ）虽低于口服高剂量组，仍足以诱导ＡＰＬ细胞分化。于是，应用１５～２０ｍｇｍ－２ｄ－１ＡＴＲＡ连续治疗２７例ＡＰＬ初发病人。在临床评价的２６例中，２４例在治疗１３～６７天内达完全缓解（ＣＲ）。无任何病人发生维甲酸综合征和ＤＩＣ。在检测的３例病人中，ＣＲ时和首次服药时的药代动力学比较发现，２例Ｃｍａｘ明显下降而１例相似。尤其重要的是，和过去一组相对匹配的高剂量ＡＴＲＡ治疗病人比较，本组结果显示低剂量ＡＴＲＡ的疗效与高剂量相似，并且可能有利于降低高白细胞血症的程度及其他一些副反应。

A clinical trial was conducted in order to evaluate the therapeutic effect and side effects of low dose all trans retinoic acid (ATRA) in the treatment of acute promyelocytic leukemia (APL). First of all, we compared the pharmacokinetic features in normal individuals with a single oral dose of ATRA at 15mg/m 2 and 45mg/m 2, respectively. The results showed that maximal plasma concentration with oral ATRA at 15mg/m 2 was high enough (10 -6 mol/L) to induce APL cell differentiation. Based on these results, 27 cases of de novo APL patients were treated with oral ATRA at a dose of 15 20mg/m 2/day and 24 of the 26(92%) evaluable cases achieved clinical complete remission (CR) after 13 to 67 dyas of ATRA treatment. No patient experienced retinoic acid syndrome (RAS) and DIC. The Cmax with a single dose of ATRA on day 1 of treatment and immediately after obtaining of CR with ATRA in three cases demonstrated similar values in one patient and an about 2 fold decrease in two patients. Moreover comparison with a relatively well matched previous group of 20 APL patients treated with high dose ATRA showed that low dose ATRA is as effective as high dose in treating APL patients and may provide the advantages of decrease of the degree of hyperleukocytosis and side effects.