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 ef fect and side-effects of low-dose ATRA in the treatment of acute promy elocytic leukemia (APL). We compared the pharmacokinetic features in n ormal 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 (10(-6) M) to induce A PL cell differentiation. Based on these results, 27 cases of de stove 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 af ter 13 to 67 days of ATRA treatment. No patient experienced RAS and DI G. The C-pmax with a single dose of ATRA on day 1 of treatment and imm ediately at CR obtained with continuous ATRA in three cases demonstrat ed similar values in one patient and an approximately two-fold decreas e in two patients. More importantly, compared with a relatively well-m atched 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 hy perleukocytosis and other side-effects.