Phase II trial of pegylated interferon alfa-2b in young patients with neurofibromatosis type 1 and unresectable plexiform neurofibromas.

Background: 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).
Methods: 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.
Results: 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). Conclusions: 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.

RCT Entities:   Population Interventions Outcomes