Gq. Chen et al., PHARMACOKINETICS AND EFFICACY OF LOW-DOSE ALL-TRANS-RETINOIC ACID IN THE TREATMENT OF ACUTE PROMYELOCYTIC LEUKEMIA, Leukemia, 10(5), 1996, pp. 825-828
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.