Phase II trial of pirfenidone in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas

Brigitte C. Widemann, Dusica Babovic-Vuksanovic, Eva Dombi, Pamela L. Wolters, Stewart Goldman, Staci Martin, Anne Goodwin, Wendy Goodspeed, Mark W. Kieran, Bruce Cohen, Susan M. Blaney, Allison King, Jeffrey Solomon, Nicholas Patronas, Frank M. Balis, Elizabeth Fox, Seth M. Steinberg, Roger J. Packer

Research output: Contribution to journalArticlepeer-review

39 Scopus citations


Background: Pirfenidone, an oral anti-inflammatory, antifibrotic agent with activity in idiopathic pulmonary fibrosis, may mediate anti-tumor activity in neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PN) by inhibition of fibroblast proliferation and collagen synthesis. The primary objective of this open label, single arm phase II trial was to evaluate the activity of pirfenidone in children and young adults with inoperable PN. Procedure: Patients (3-21 years) with NF1-related progressive PN received pirfenidone at the previously determined optimal dose (500mg/m2 orally, q8h) on a continuous dosing schedule (one cycle=28 days). Volumetric MRI analysis was used to assess response. Progression was defined as ≥20% PN volume increase compared to baseline. Pirfenidone would be considered active if it doubled the median time to progression (TTP) compared to the TTP on the placebo arm of a phase II trial with the farnesyltransferase inhibitor tipifarnib, which used near identical eligibility criteria. Toxicities, objective response rate, and quality of life (QOL) also were evaluated. Results: Thirty-six patients were enrolled and tolerated pirfenidone well with intermittent nausea and vomiting as the most frequent toxicities. A dose reduction was required in only three patients. The median TTP for pirfenidone was 13.2 months compared to 10.6 months for the placebo control group from the tipifarnib trial (two-tailed P=0.92; one-tailed P=0.46). No objective responses were observed. Conclusions: Pirfenidone was well tolerated, but did not demonstrate activity as defined in this trial and does not warrant further evaluation in children with NF1 and progressive PN.

Original languageEnglish (US)
Pages (from-to)1598-1602
Number of pages5
JournalPediatric Blood and Cancer
Issue number9
StatePublished - Sep 2014


  • Neurofibromatosis type 1
  • Phase II trial
  • Plexiform neurofibroma
  • Progression free survival
  • Time to progression
  • Volumetric MRI analysis

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Hematology
  • Oncology


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