Medline ® Abstract for Reference 38
of 'Neurofibromatosis type 1 (NF1): Management and prognosis'
Phase II trial of pegylated interferon alfa-2b in young patients with neurofibromatosis type 1 and unresectable plexiform neurofibromas.
Jakacki RI, Dombi E, Steinberg SM, Goldman S, Kieran MW, Ullrich NJ, Pollack IF, Goodwin A, Manley PE, Fangusaro J, Allen R, Widemann BC
Neuro Oncol. 2017;19(2):289.
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.
Children's Hospital of Pittsburgh, 4401 Penn Ave. Pittsburgh, Pennsylvania 15224 (R.I.J.*, I.F.P.); Pediatric Oncology Branch (E.D., A.G., B.W.) and Biostatistics and Data Management Section (SS), Center for Cancer Research, National Cancer Institute, Building 10, Bethesda, Maryland 20892; Ann and Robert Lurie Children's Hospital, 225 E. Chicago Ave., Chicago, Illinois 60611 (S.G., J.F., R.A.); Dana-Farber/Boston Children's Cancer and Blood Disorders Center, 450 Brookline Avenue, Boston, Massachusetts 02215 (M.W.K., P.E.M., N.J.U.).