Characteristics of children enrolled in treatment trials for NF1-related plexiform neurofibromas
1National Cancer Institute, Pediatric Oncology Branch, NIH, Bethesda, MD 20892, USA. kimaer@mail.nih.gov
Insights
Children with neurofibromatosis type 1 (NF1) plexiform neurofibromas (PN) in clinical trials have large tumors and complications. These trials offer valuable data on drug tolerance and pharmacokinetics in young patients.
Area of Science:
- Pediatric Oncology
- Clinical Trial Design
- Genetics
Background:
- Neurofibromatosis type 1 (NF1) is a genetic disorder associated with plexiform neurofibromas (PN).
- PN can cause significant morbidity and complications in children.
- Early phase clinical trials are crucial for evaluating novel therapies in pediatric populations.
Purpose of the Study:
- To characterize children with NF1-related PN in treatment trials.
- To assess PN tumor burden, complications, and treatment outcomes.
- To compare NF1 patient characteristics with those of pediatric cancer patients in early phase trials.
Main Methods:
- Retrospective analysis of 59 children with NF1-related PN treated on clinical trials (1996-2007).
- Analysis of pre-enrollment characteristics and PN complications.
- Outcome analysis in 19 patients from phase I trials.
- Comparison with a cohort of pediatric cancer patients.
Main Results:
- Median age at enrollment was 8 years; median PN volume was 555 mL.
- Common complications included pain (53%), other tumors (18%), and hypertension (8%).
- NF1 patients were younger, had better performance scores, less prior therapy, and longer study duration than cancer patients.
Conclusions:
- Children with NF1-related PN in trials present with large tumors and significant morbidity.
- Clinical trials provide essential data on drug tolerance, toxicity, and pharmacokinetics in young NF1 patients.
- Findings may inform the adaptation of pediatric cancer trial designs and endpoints for NF1-related PN.
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.
