title: Pharmacokinetics of low-dose all-trans retinoic acid in Japanese children with cancer.
abstract: 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.
authors.affiliation: Department of Pediatrics, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan. ped016@poh.osaka-med.ac.jp
authors.forename: Kimitaka
authors.initials: K
authors.lastname: Takitani
authors.forename: Akiko
authors.initials: A
authors.lastname: Inoue
authors.forename: Maki
authors.initials: M
authors.lastname: Koh
authors.forename: Chihiro
authors.initials: C
authors.lastname: Kawakami
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kuno
authors.forename: Naohisa
authors.initials: N
authors.lastname: Kawamura
authors.forename: Munenori
authors.initials: M
authors.lastname: Miyake
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamai
mesh_terms: 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*
chemical_list: D014212:Tretinoin