Phase II trial of pirfenidone in adults with neurofibromatosis type 1

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with an incidence of 1: 3,000. The major sources of morbidity and mortality in patients with NF1 are plexiform neurofibromas (PNs) and paraspinal neurofibromas (PSNs).(1,2) The histopathology of neurofibromas is complex, with diverse cellular content and a large amount of fibrous tissue. Several studies imply that fibroblasts have a role in pathogenesis of these tumors.(3) This leads to a hypothesis that an antifibrotic may exert a therapeutic effect in NF1. Pirfenidone (Solanan Inc., Dallas, TX), 5-methyl-1-phenyl-2-(1H)-pyridone, is an oral drug with known antifibrotic effects. We recently showed that oral pirfenidone significantly inhibits survival of human neurofibroma xenografts in SCID mice.(4) No mortality or signs of drug toxicity were noted in treated animals.