1. Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia.
- Author
-
Chen GQ, Shen ZX, Wu F, Han JY, Miao JM, Zhong HJ, Li XS, Zhao JQ, Zhu J, Fang ZW, Chen SJ, Chen Z, and Wang ZY
- Subjects
- Administration, Oral, Adult, Female, Half-Life, Humans, Immunologic Factors adverse effects, Immunologic Factors therapeutic use, Leukemia, Promyelocytic, Acute mortality, Leukocytosis chemically induced, Male, Middle Aged, Remission Induction, Tretinoin administration & dosage, Tretinoin adverse effects, Tretinoin therapeutic use, Immunologic Factors pharmacokinetics, Leukemia, Promyelocytic, Acute therapy, Tretinoin pharmacokinetics
- Abstract
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/m2 and 45 mg/m2, respectively. The results showed that maximal plasma concentration (Cpmax) with oral 15 mg/m2 ATRA was high enough (10(-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/m2/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 Cpmax 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.
- Published
- 1996