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 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.
Chen
G Q
GQ
Shanghai Institute of Hematology, China.
Shen
Z X
ZX
Wu
F
F
Han
J Y
JY
Miao
J M
JM
Zhong
H J
HJ
Li
X S
XS
Zhao
J Q
JQ
Zhu
J
J
Fang
Z W
ZW
Chen
S J
SJ
Chen
Z
Z
Wang
Z Y
ZY
D000284:Administration, Oral; D000328:Adult; D005260:Female; D006207:Half-Life; D006801:Humans; D007155:Immunologic Factors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015473:Leukemia, Promyelocytic, Acute / Q000401:mortality / Q000628:therapy*; D007964:Leukocytosis / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D012074:Remission Induction; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
D007155:Immunologic Factors; D014212:Tretinoin