title: Phase II trial of pegylated interferon alfa-2b in young patients with neurofibromatosis type 1 and unresectable plexiform neurofibromas.
abstract: There is no proven medical therapy for plexiform neurofibromas (PNs). We undertook a phase II trial of pegylated interferon (PI) to evaluate response and time to progression (TTP).
  
  
  
  PI was administered as a subcutaneous injection to patients with neurofibromatosis type 1‒related PN, stratified by the presence of symptoms (asymptomatic: stratum 1, symptomatic: stratum 2) or documented imaging progression (stratum 3). Patients in strata 1 and 2 received PI for up to one year if stable, 2 years for those with clinical (stratum 2) or imaging response (≥20% decrease in volume). Patients on stratum 3 continued PI until progression. PI was considered active in stratum 3 if TTP doubled compared with the placebo arm of a previous randomized trial using tipifarnib.
  
  
  
  Enrolled were 82 evaluable patients (median age 10 y; range 1.6 to 21.4). Fatigue and/or worsening of behavioral issues were the most common toxicities requiring dose modification. Across all strata, imaging responses were seen in 4 patients (5%). Three of 26 symptomatic patients on stratum 2 met the criteria for clinical response without corresponding imaging changes. In stratum 3, median TTP was 29.4 months versus 11.8 for the placebo arm of the previous trial (P=.031). The slope of tumor growth on PI slowed significantly compared with the slope before starting PI (P=.044).
  
  
  
  In patients with active PN, PI results in more than doubling of the TTP compared with placebo. Imaging changes in symptomatic patients were not associated with changes in clinical status.
authors: Children's Hospital of Pittsburgh, 4401 Penn Ave. Pittsburgh, Pennsylvania, USA.
authors: Regina I
authors: RI
authors: Jakacki
authors: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Eva
authors: E
authors: Dombi
authors: Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Seth M
authors: SM
authors: Steinberg
authors: Ann and Robert Lurie Children's Hospital, 225 E. Chicago Ave., Chicago, Illinois, USA.
authors: Stewart
authors: S
authors: Goldman
authors: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, USA.
authors: Mark W
authors: MW
authors: Kieran
authors: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, USA.
authors: Nicole J
authors: NJ
authors: Ullrich
authors: Children's Hospital of Pittsburgh, 4401 Penn Ave. Pittsburgh, Pennsylvania, USA.
authors: Ian F
authors: IF
authors: Pollack
authors: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Anne
authors: A
authors: Goodwin
authors: Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts, USA.
authors: Peter E
authors: PE
authors: Manley
authors: Ann and Robert Lurie Children's Hospital, 225 E. Chicago Ave., Chicago, Illinois, USA.
authors: Jason
authors: J
authors: Fangusaro
authors: Ann and Robert Lurie Children's Hospital, 225 E. Chicago Ave., Chicago, Illinois, USA.
authors: Rudy
authors: R
authors: Allen
authors: Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
authors: Brigitte C
authors: BC
authors: Widemann
mesh_terms: D000293:Adolescent; D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D009367:Neoplasm Staging; D018318:Neurofibroma, Plexiform / Q000188:drug therapy* / Q000473:pathology; D009456:Neurofibromatosis 1 / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b
keywords: clinical trials; interferon; neurofibromatosis type 1; pediatrics; plexiform neurofibromas