title: Combination of cladribine plus topotecan for recurrent or refractory pediatric acute myeloid leukemia.
abstract: BACKGROUND
  The prognosis after recurrence of pediatric acute myeloid leukemia (AML) is poor, and effective salvage regimens are urgently needed.
  
  
  METHODS
  In phase 1 and pilot studies, the authors evaluated the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of a 5-day course of cladribine followed by topotecan in pediatric patients with recurrent/refractory AML. The cladribine dose was escalated as follows: 9.1, 13.6, 16.3, and 19.5 mg/m(2) per day (8.9 mg/m(2) per day in the pilot study). Outcome was analyzed according to the absence (Stratum 1) versus presence (Stratum 2) of previous allogeneic hematopoietic stem cell transplantation. Twenty-six patients (20 in Stratum 1 and 6 in Stratum 2) were treated.
  
  
  RESULTS
  The MTD was not reached in Stratum 1, but a DLT occurred at the lowest cladribine dosage (9.1 mg/m(2) per day) in Stratum 2. Febrile neutropenia was common in both strata. Nine (34.6%) of 26 patients experienced a complete response, and 7 (30.4%) achieved a partial response; 5 (19.2%) were long-term survivors at the time of last follow-up. Clinical outcome was not associated with cladribine or topotecan systemic exposure.
  
  
  CONCLUSIONS
  The combination was well tolerated in Sratum 1, and the response rate was encouraging. This regimen offers a postrecurrence treatment alternative for patients, especially those who have received anthracycline-containing chemotherapy.
authors.affiliation: Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. hiroto.inaba@stjude.org
authors.forename: Hiroto
authors.initials: H
authors.lastname: Inaba
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Crews
authors.forename: Shengping
authors.initials: S
authors.lastname: Yang
authors.forename: Stanley
authors.initials: S
authors.lastname: Pounds
authors.forename: Ching-Hon
authors.initials: CH
authors.lastname: Pui
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Rubnitz
authors.forename: Bassem I
authors.initials: BI
authors.lastname: Razzouk
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D017338:Cladribine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D012008:Recurrence; D019233:Retreatment; D019772:Topotecan / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D017338:Cladribine; D019772:Topotecan