Pharmacokinetics of low-dose all-trans retinoic acid in Japanese children with cancer.
All-trans retinoic acid (ATRA) is used as differentiation therapy for acute promyelocytic leukemia (APL). The two major adverse effects of ATRA therapy are hyperleukocytosis and retinoic acid syndrome. In order to prevent these adverse effects, low-dose ATRA therapy (25 mg/m2/d) has been tried in adults. Accordingly we assessed the pharmacokinetics of low-dose ATRA in children with cancer. Four children (one with APL and three with other advanced cancer) were administered ATRA and its pharmacokinetics were evaluated. In three patients, the pharmacokinetic parameters of ATRA were similar to those previously determined for APL patients in remission, but the values were lower in one patient. Low-dose ATRA was effective for APL, but not for the solid tumors. This therapy did not cause any severe toxicity. Further studies are needed to determine the optimum ATRA regimen and to evaluate low-dose ATRA combined with chemotherapy in children with APL.
Takitani
Kimitaka
K
Department of Pediatrics, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan. ped016@poh.osaka-med.ac.jp
Inoue
Akiko
A
Koh
Maki
M
Kawakami
Chihiro
C
Kuno
Tomoko
T
Kawamura
Naohisa
N
Miyake
Munenori
M
Tamai
Hiroshi
H
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007564:Japan; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy*; D007964:Leukocytosis / Q000139:chemically induced; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D012074:Remission Induction; D014212:Tretinoin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*
D014212:Tretinoin