[Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia].
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 15 mg/m2 and 45 mg/m2, respectively. The results showed that maximal plasma concentration with oral ATRA at 15 mg/m2 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 15-20 mg/m2/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.
Chen
G
G
Shanghai Institute of Hematology, Ruijin Hospital, Shanghai Second Medical University.
Shen
Z
Z
Zhu
A P
AP
D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy* / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D014212:Tretinoin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D014212:Tretinoin