Phase II pilot study of imatinib mesylate in neurofibromatosis (NF1) patients with plexiform neurofibromas.

10030 Background: NF1 is a common inherited disorder resulting from mutations in the neurofibromin gene resulting in a variety of tumors. PN occur in 20-40% of NF1 patients and result from loss of heterozygosity of neurofibromin in Schwann cells. PNs are refractory to conventional chemotherapy and often unresectable. Pre-clinical studies and clinical reports have defined the role of the c-KIT receptor, c-ABL, and PDGFR tyrosine kinases in PN growth and response to the tyrosine kinase inhibitor imatinib. Methods: We conducted a phase II pilot study to examine the response of measurable, clinically significant PNs in NF1 patients to imatinib. The primary 6 month endpoint was PN size by MRI cross sectional area: responsive > 5% reduction; progression > 5% increase; stable < 5% change. Secondary endpoints included symptomatic improvement, expression of 15 plasma cytokines, and safety/toxicity of imatinib. Results: 36 pediatric/adult NF1 patients with PNs were enrolled and treated with imatinib; 440 mg/m2/day ...