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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
Article first published online: 11 OCT 2007
Copyright © 2007 American Cancer Society
Volume 110, Issue 11, pages 2535–2541, 1 December 2007
How to Cite
Fouladi, M., Nicholson, H. S., Zhou, T., Laningham, F., Helton, K. J., Holmes, E., Cohen, K., Speights, R. A., Wright, J. and Pollack, I. F. (2007), 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. Cancer, 110: 2535–2541. doi: 10.1002/cncr.23078
- Issue published online: 19 NOV 2007
- Article first published online: 11 OCT 2007
- Manuscript Accepted: 13 JUL 2007
- Manuscript Revised: 22 JUN 2007
- Manuscript Received: 16 APR 2007
- National Cancer Institute. Grant Number: U01 CA97452
- National Center for Research Resources. Grant Number: M01 RR00188
- recurrent central nervous system malignancies;
- Phase II trial;
- farnesyl transferase inhibitor
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), and diffuse intrinsic brainstem glioma (BSG).
Between January 2004 and July 2005, patients were enrolled and stratified as follows: Stratum 1, recurrent or refractory MB/PNET; Stratum 2, recurrent or refractory HGG; and Stratum 3, recurrent or refractory BSG. Patients received tipifarnib 200 mg/m2 per dose twice daily for 21 days repeated every 28 days. Patients who received enzyme-inducing anticonvulsants and other CYP3A4/5 inducers or inhibitors were excluded. The primary objective was to estimate the sustained response rate in all strata.
Ninety-seven patients with a median age of 11.2 years (range, 3.2–21.9 years) were enrolled on the study, and 81 patients were evaluable for response. One of 35 patients with BSG and 1 of 31 patients with HGG had a sustained partial response. No responses were observed in 15 patients with MB/PNET. Eight patients (3 HGG, 1 MB, and 4 BSG) remained stable for ≥4 courses (range, 4–25 courses). The median number of courses received was 2 (range, 1–25 courses). The most frequent grade 3 and 4 toxicities included neutropenia (18.7%), thrombocytopenia (14.3%), and leukopenia (14.3%). The 6-month progression-free survival rate (±standard deviation) was 14% ± 6% for HGG, 6% ± 6% for MB/PNET and 3% ± 3% for BSG.
Tipifarnib tolerated well but had little activity as a single agent in children with recurrent central nervous system malignancies. Cancer 2007. © 2007 American Cancer Society.