Effectiveness and pharmacokinetics of low-dose all-trans retinoic acid (25 mg/m2) in acute promyelocytic leukemia.
It has been shown that all-trans retinoic acid (ATRA) at doses of 45 to 100 mg/m2/d induces complete remission (CR) of acute promyelocytic leukemia (APL) by a differentiation process. To date, ATRA dose-ranging studies have not yet been evaluated. Thus, we initiated in May 1990 a multicenter study with ATRA at a lower dose of 25 mg/m2/d until CR. Thirty patients with APL were treated with ATRA, of whom 12 were previously untreated, 14 were in first relapse, and 4 had failed after conventional first induction chemotherapy. Twenty-four of 30 achieved CR, 3 failed, and 3 died before day 30. Median time to CR was 45 days. Hyperleucocytosis (14 to 43 x 10(9) white blood cells per liter) was observed in 9 patients between days 10 and 23. Clinical complications that may have been related to the retinoic acid syndrome were observed in 8 patients, of whom 3 died. Pharmacokinetics studies were performed in 5 patients. Peak plasma concentrations and mean area under the concentration-time curve were not lower than previous levels obtained under the 45 mg/m2 dose. Overall, our study shows that there is no difference in terms of therapeutic efficacy, triggering of hyperleukocytosis, or retinoic acid syndrome and pharmacokinetic results with ATRA at 25 or 45 mg/m2/d.
Castaigne
S
S
Department of Hematology, Hopital Saint Louis, Paris, France.
Lefebvre
P
P
Chomienne
C
C
Suc
E
E
Rigal-Huguet
F
F
Gardin
C
C
Delmer
A
A
Archimbaud
E
E
Tilly
H
H
Janvier
M
M
D000284:Administration, Oral; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000097:blood / Q000188:drug therapy*; D007958:Leukocyte Count / Q000187:drug effects; D012008:Recurrence; D013997:Time Factors; D014212:Tretinoin / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*
D014212:Tretinoin