title: Phase 2 trial of sorafenib in children and young adults with refractory solid tumors: A report from the Children's Oncology Group.
abstract: BACKGROUND
  Sorafenib is an oral small molecule inhibitor of multiple kinases controlling tumor growth and angiogenesis. The purpose of the phase 2 study was to determine the response rate of sorafenib and gain further information on the associated toxicities, pharmacokinetics, and pharmacodynamics of sorafenib in children and young adults with relapsed or refractory tumors including rhabdomyosarcoma, Wilms tumor, hepatocellular carcinoma (HCC), and papillary thyroid carcinoma (PTC).
  
  
  METHODS
  Sorafenib, 200 mg/m(2) /dose, was administered every 12 hr continuously for 28 day cycles using a two-stage design in two primary strata (rhabdomyosarcoma and Wilms tumor) and two secondary strata (HCC and PTC). Correlative studies in consenting patients included determination of sorafenib steady state trough concentrations and assessments of VEGF and sVEGFR2.
  
  
  RESULTS
  Twenty patients (median age of 11 years; range, 5-21) enrolled. No objective responses (RECIST) were observed in the 10 evaluable patients enrolled in each of the two primary disease strata of rhabdomyosarcoma and Wilms tumor. No patients with HCC or PTC were enrolled. Sorafenib was not associated with an excessive rate of dose-limiting toxicity (DLT). The mean ± SD steady state concentration during cycle 1 day 15 was 6.5 ± 3.9 μg/ml (n = 10).
  
  
  CONCLUSIONS
  Sorafenib was well tolerated in children at 200 mg/m(2) /dose twice daily on a continuous regimen with toxicity profile and steady state drug concentrations similar to those previously reported. Single agent sorafenib was inactive in children with recurrent or refractory rhabdomyosarcoma or Wilms tumor.
authors.affiliation: Children's National Medical Center, Washington, District of Columbia.
authors.forename: AeRang
authors.initials: A
authors.lastname: Kim
authors.affiliation: Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Brigitte C
authors.initials: BC
authors.lastname: Widemann
authors.affiliation: Children's Oncology Group Statistics, Monrovia, California.
authors.forename: Mark
authors.initials: M
authors.lastname: Krailo
authors.affiliation: Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland.
authors.forename: Nalini
authors.initials: N
authors.lastname: Jayaprakash
authors.affiliation: Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Fox
authors.affiliation: University of Minnesota Medical Center, Minneapolis, Minnesota.
authors.forename: Brenda
authors.initials: B
authors.lastname: Weigel
authors.affiliation: Baylor College of Medicine, Houston, Texas.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Blaney
mesh_terms: D000293:Adolescent; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D008297:Male; D009363:Neoplasm Proteins / Q000097:blood; D009536:Niacinamide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012208:Rhabdomyosarcoma / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D016879:Salvage Therapy; D000077157:Sorafenib; D017211:Treatment Failure; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood; D009396:Wilms Tumor / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000077157:Sorafenib; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: pediatrics; solid tumors; sorafenib