title: Phase I trial of lenalidomide in pediatric patients with recurrent, refractory, or progressive primary CNS tumors: Pediatric Brain Tumor Consortium study PBTC-018.
abstract: OBJECTIVE
  A phase I trial of lenalidomide was performed in children with recurrent, refractory, or progressive primary CNS tumors to estimate the maximum-tolerated dose (MTD) and to describe the toxicity profile and pharmacokinetics.
  
  
  METHODS
  Lenalidomide was administered by mouth daily for 21 days, repeated every 28 days. The starting dose was 15 mg/m(2)/d orally, and the dose was escalated according to a modified continuous reassessment method. Correlative studies included pharmacokinetics obtained from consenting patients on course 1, day 1, and at steady-state (between days 7 and 21).
  
  
  RESULTS
  Fifty-one patients (median age, 10 years; range, 2 to 21 years) were enrolled. Forty-four patients were evaluable for dose finding, and 49 patients were evaluable for toxicity. The primary toxicity was myelosuppression, but the MTD was not defined because doses up to 116 mg/m(2)/d were well-tolerated during the dose-finding period. Two objective responses were observed (one in thalamic juvenile pilocytic astrocytoma and one in optic pathway glioma) at dose levels of 88 and 116 mg/m(2)/d. Twenty-three patients, representing all dose levels, received ≥ six cycles of therapy. Pharmacokinetic analysis demonstrated that the lenalidomide area under the concentration-time curve from 0 to 24 hours and maximum plasma concentration increased with dosage over the range studied.
  
  
  CONCLUSIONS
  Lenalidomide was tolerable in children with CNS tumors at doses of 116 mg/m(2)/d during the initial dose-finding period. The primary toxicity is myelosuppression. Antitumor activity, defined by both objective responses and long-term stable disease, was observed, primarily in patients with low-grade gliomas.
authors.affiliation: National Cancer Institute, Pediatric Oncology Branch, Bldg 10 CRC, Rm 1-5750, Bethesda, MD 20892-1104, USA. warrenk@mail.nih.gov
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Warren
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: Jason
authors.initials: J
authors.lastname: Fangusaro
authors.forename: Paula
authors.initials: P
authors.lastname: Schaiquevich
authors.forename: Clinton F
authors.initials: CF
authors.lastname: Stewart
authors.forename: Dana
authors.initials: D
authors.lastname: Wallace
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
authors.forename: Roger
authors.initials: R
authors.lastname: Packer
authors.forename: Tobey
authors.initials: T
authors.lastname: Macdonald
authors.forename: Regina
authors.initials: R
authors.lastname: Jakacki
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D020714:Maximum Tolerated Dose; D012008:Recurrence; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D013792:Thalidomide; D000077269:Lenalidomide