Characteristics of children enrolled in treatment trials for NF1-related plexiform neurofibromas

OBJECTIVE:: To describe the characteristics of children enrolled in treatment trials for neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN), PN tumor burden, PN-related complications, and treatment outcomes and to highlight the differences between characteristics of children with NF1 vs children with cancers entered on early phase drug trials. METHODS:: Pre-enrollment characteristics and complications of PN were retrospectively analyzed in a cohort of 59 children with NF1-related PN treated on 1 of 7 clinical trials at the NIH between 1996 and 2007. Outcome was analyzed in a subset of 19 patients enrolled in phase I trials. Comparisons to children with cancer were made from a similar analysis performed recently. RESULTS:: The median age at enrollment was 8 years. The median PN volume was 555 mL. Most patients had no prior chemotherapy or radiation, but nearly half had previous surgery for PN. PN-associated complications and NF1 manifestations were common, including pain (53%), other tumors (18%), and hypertension (8%). Investigational drug therapy was well tolerated. A median of 10 treatment cycles was administered. Patients with NF1-related PN were younger, had better performance score, had less prior therapy, and remained on study longer than cancer patients. CONCLUSIONS:: Children with NF1-related plexiform neurofibroma (PN) enrolled in clinical trials had large tumors with substantial morbidity. Clinical trials in these children provide information about drug tolerance, cumulative toxicity, and pharmacokinetics in a younger population than early phase pediatric cancer trials. This report may aid in the evaluation of the applicability of traditional pediatric cancer trial designs and endpoints for NF1-related PN.