Phase I trial of pegylated interferon-α-2b in young patients with plexiform neurofibromas

Objective: Interferon has antiproliferative and antiangiogenic properties. We sought to evaluate preliminary efficacy and determine the recommended phase II dose (RP2D) for pegylated interferon-α-2b (PI) in patients with unresectable progressive or symptomatic plexiform neurofibromas (PN).

Methods: PI was administered weekly in cohorts of 3–6 patients during the dose-finding phase and continued for up to 2 years. Twelve patients were treated at the RP2D to further evaluate toxicity and activity.

Results: Thirty patients (median age 9.3 years, range 1.9–34.7 years) were enrolled. No dose-limiting toxicity (DLT) was seen in patients treated at the 3 μg/kg dose level (DL) during the first 4 weeks. All 5 patients treated at the 4.5 μg/kg DL came off study or required dose reductions for behavioral toxicity or fatigue. Similar DLT on the 3 μg/kg DL became apparent over time. There was 1 DLT (myoclonus) in 12 patients enrolled at the 1.0 μg/kg DL. Eleven of 16 patients with pain showed improvement and 13 of 14 patients with a palpable mass had a decrease in size. Five of 17 patients (29%) who underwent volumetric analysis had a 15%–22% decrease in volume. Three of 4 patients with documented radiographic progression prior to enrollment showed stabilization or shrinkage.

Conclusions: The RP2D of PI for pediatric patients with PN is 1 μg/kg/wk. Clinical and radiographic improvement and cessation of growth can occur.

Classification of evidence: This study provides Class III evidence that pegylated interferon-α-2b in patients with unresectable, progressive, symptomatic, or life-threatening PNs results in radiographic reduction or stabilization of PN size.