Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia
Chen, G.Q.; Shen, Z.X.; Wu, F.; Han, J.Y.; Miao, J.M.; Zhong, H.J.; Li, X.S.; Zhao, J.Q.; Zhu, J.; Fang, Z.W.; Chen, S.J.; Chen, Z.; Wang, Z.Y.
Leukemia 10(5): 825-828
1996
ISSN/ISBN: 0887-6924 PMID: 8656678 Document Number: 464154
A clinical trial was conducted in order to evaluate the therapeutic effect and side-effects of low-dose ATRA in the treatment of acute promyelocytic leukemia (APL). We compared the pharmacokinetic features in normal individuals with single oral ATRA at 15 mg/m-2 and 45 mg/m-2, respectively. The results showed that maximal plasma concentration (C-pmax) with oral 15 mg/m-2 ATRA was high enough (1 0-6 M) to induce APL cell differentiation. Based on these results, 27 cases of de novo APL patients were treated with continuous oral ATRA at the dose of 15-20 mg/m-2/day and 24/26 evaluable cases (92%) achieved clinical CR after 13 to 67 days of ATRA treatment. No patient experienced RAS and DIC. The C-pmax with a single dose of ATRA on day 1 of treatment and immediately at CR obtained with continuous ATRA in three cases demonstrated similar values in one patient and an approximately two-fold decrease in two patients. More importantly, compared with a relatively well-matched historic group of 20 APL patients treated with high-dose ATRA, our results suggest that low-dose ATRA is as effective as high-dose in treating APL patients and may provide advantages through decreased hyperleukocytosis and other side-effects.