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Abstract
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.
Footnotes
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Study funding: Supported by Schering-Plough Corp., who supplied the pegylated interferon-α-2b.
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- AUC
- area under the curve
- DL
- dose level
- DLT
- dose-limiting toxicity
- FDA
- Food and Drug Administration
- IFN
- interferon
- MTD
- maximum tolerated dose
- NF1
- neurofibromatosis type 1
- NHT
- nonhematologic toxicity
- PEG
- polyethylene glycol
- PI
- pegylated interferon-α-2b
- PN
- plexiform neurofibroma
- RP2D
- recommended phase II dose
- STIR
- short T1-inversion recovery
- TSH
- thyroid-stimulating hormone
- VA
- volumetric analyses.
- Received March 12, 2010.
- Accepted September 17, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
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