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.
Kim
A
A
National Cancer Institute, Pediatric Oncology Branch, NIH, Bethesda, MD 20892, USA. kimaer@mail.nih.gov
Gillespie
A
A
Dombi
E
E
Goodwin
A
A
Goodspeed
W
W
Fox
E
E
Balis
F M
FM
Widemann
B C
BC
D000008:Abdominal Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D000293:Adolescent; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D015331:Cohort Studies; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000209:etiology; D007223:Infant; D008297:Male; D018318:Neurofibroma, Plexiform / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009456:Neurofibromatosis 1 / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D010146:Pain / Q000209:etiology; D012189:Retrospective Studies; D013899:Thoracic Neoplasms / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D016896:Treatment Outcome; D055815:Young Adult
D000970:Antineoplastic Agents