title: Phase II study of oral capsular 4-hydroxyphenylretinamide (4-HPR/fenretinide) in pediatric patients with refractory or recurrent neuroblastoma: a report from the Children's Oncology Group.
abstract: OBJECTIVE
  To determine the response rate to oral capsular fenretinide in children with recurrent or biopsy proven refractory high-risk neuroblastoma.
  
  
  METHODS
  Patients received 7 days of fenretinide: 2,475 mg/m(2)/d divided TID (<18 years) or 1,800 mg/m(2)/d divided BID (≥18 years) every 21 days for a maximum of 30 courses. Patients with stable or responding disease after course 30 could request additional compassionate courses. Best response by course 8 was evaluated in stratum 1 (measurable disease on CT/MRI ± bone marrow and/or MIBG avid sites) and stratum 2 (bone marrow and/or MIBG avid sites only).
  
  
  RESULTS
  Sixty-two eligible patients, median age 5 years (range 0.6-19.9), were treated in stratum 1 (n = 38) and stratum 2 (n = 24). One partial response (PR) was seen in stratum 2 (n = 24 evaluable). No responses were seen in stratum 1 (n = 35 evaluable). Prolonged stable disease (SD) was seen in 7 patients in stratum 1 and 6 patients in stratum 2 for 4 to 45+ (median 15) courses. Median time to progression was 40 days (range 17-506) for stratum 1 and 48 days (range 17-892) for stratum 2. Mean 4-HPR steady-state trough plasma concentrations were 7.25 μmol/L (coefficient of variation 40-56%) at day 7 course 1. Toxicities were mild and reversible.
  
  
  CONCLUSIONS
  Although neither stratum met protocol criteria for efficacy, 1 PR + 13 prolonged SD occurred in 14/59 (24%) of evaluable patients. Low bioavailability may have limited fenretinide activity. Novel fenretinide formulations with improved bioavailability are currently in pediatric phase I studies.
authors: Children's Hospital Los Angeles, Department of Pediatrics, Keck School of Medicine, University of Southern California, Los Angeles, California 90027, USA. jvillablanca@chla.usc.edu
authors: Judith G
authors: JG
authors: Villablanca
authors: Wendy B
authors: WB
authors: London
authors: Arlene
authors: A
authors: Naranjo
authors: Patrick
authors: P
authors: McGrady
authors: Matthew M
authors: MM
authors: Ames
authors: Joel M
authors: JM
authors: Reid
authors: Renee M
authors: RM
authors: McGovern
authors: Sarah A
authors: SA
authors: Buhrow
authors: Hollie
authors: H
authors: Jackson
authors: Enno
authors: E
authors: Stranzinger
authors: Brenda J
authors: BJ
authors: Kitchen
authors: Paul M
authors: PM
authors: Sondel
authors: Marguerite T
authors: MT
authors: Parisi
authors: Barry
authors: B
authors: Shulkin
authors: Gregory A
authors: GA
authors: Yanik
authors: Susan L
authors: SL
authors: Cohn
authors: C Patrick
authors: CP
authors: Reynolds
mesh_terms: D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics; D000284:Administration, Oral; D000293:Adolescent; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D002214:Capsules; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D017313:Fenretinide / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D007223:Infant; D007457:Iodine Radioisotopes; D008279:Magnetic Resonance Imaging; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000188:drug therapy*; D009447:Neuroblastoma / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015996:Survival Rate; D014057:Tomography, X-Ray Computed; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D017313:Fenretinide; D019797:3-Iodobenzylguanidine