A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high‐grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma: A children's oncology group study

摘要: BACKGROUND. An open-label Phase II study of tipifarnib was conducted to evaluate its safety and efficacy in children with recurrent or refractory medulloblastoma (MB)/primitive neuroectodermal tumor (PNET), high-grade glioma (HGG), diffuse intrinsic brainstem (BSG). METHODS. Between January 2004 July 2005, patients were enrolled stratified as follows: Stratum 1, MB/PNET; 2, HGG; 3, BSG. Patients received 200 mg/m2 per dose twice daily for 21 days repeated every 28 days. who enzyme-inducing anticonvulsants other CYP3A4/5 inducers inhibitors excluded. The primary objective estimate the sustained response rate all strata. RESULTS. Ninety-seven a median age 11.2 years (range, 3.2–21.9 years) on study, 81 evaluable response. One 35 BSG 1 31 HGG had partial No responses observed 15 MB/PNET. Eight (3 HGG, MB, 4 BSG) remained stable ≥4 courses 4–25 courses). number 2 1–25 most frequent grade 3 toxicities included neutropenia (18.7%), thrombocytopenia (14.3%), leukopenia (14.3%). 6-month progression-free survival (±standard deviation) 14% ± 6% MB/PNET 3% BSG. CONCLUSIONS. Tipifarnib tolerated well but little activity single agent central nervous system malignancies. Cancer 2007. © 2007 American Society.