Sequential oral hydroxyurea and intravenous cytosine arabinoside in refractory childhood acute leukemia: a pediatric oncology group phase 1 study. J Pediatr Hematol Oncol 2008 May;30(5):353-7
Date
05/07/2008Pubmed ID
18458568Pubmed Central ID
PMC4601800DOI
10.1097/MPH.0b013e318166247eScopus ID
2-s2.0-43149099423 (requires institutional sign-in at Scopus site) 5 CitationsAbstract
At concentrations >0.1 mM, hydroxyurea (HU) enhances the accumulation of cytosine arabinoside (ara-C) in leukemia cells in vitro. This study of children with refractory acute leukemia was designed to take advantage of this biochemical modulation. A fixed dose of HU and an escalating dose of ara-C were used. Oral HU (1200 mg/m2) was followed 2 hours later by ara-C (250-3100 mg/m2) intravenously in 15 minutes. The combination was given on days 1, 2, 3 and 8, 9, 10. Thirty-three children [26 acute lymphocytic leukemia (ALL), 7 acute nonlymphocytic leukemia] were treated; 29 received at least 1 full course. All patients developed grade 4 cytopenias. Other grade 3 to 4 toxicities included hyperbilirubinemia (2), elevated transaminases (3), transient gait disturbance (1), stomatitis (3), typhlitis (1), nausea/vomiting (9), and marrow aplasia >4 weeks (1). Three patients had intracranial bleeds while thrombocytopenic. Only liver toxicities and nausea/vomiting exhibited any dosage effect. The maximum tolerated dose of ara-C was 2400 mg/m2. There were 6 complete responses (5 ALL), 5 partial responses (3 ALL), and 19 patients with no response or progressive disease. There was no dosage effect for response with 2 complete responses occurring at the lowest ara-C level. Responses were transient (1 to 3 mo). Twenty of twenty-six patients achieved a peak serum HU level >0.5 mM by 2 hours after the HU dose. The mean level at 2 hours was 0.57 mM (range: 0.21 to 0.99 mM). This combination of HU and ara-C is tolerable and has efficacy in refractory leukemias. Responses at the lowest ara-C dose level suggests synergism.
Author List
Dubowy R, Graham M, Hakami N, Kletzel M, Mahoney D, Newman E, Ravindranath Y, Camitta BAuthor
Bruce m. Camitta Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdolescentAdult
Child
Child, Preschool
Cytarabine
Humans
Hydroxyurea
Leukemia
Leukemia, Myeloid, Acute
Leukemia-Lymphoma, Adult T-Cell
Liver
Skin
Survival Analysis
