Neuro-oNcology

The purpose of this study is to estimate the maximum-tolerated dose (MTD) and describe toxicities and pre-liminary clinical effects of tipifarnib, a farnesyltrans-ferase (FTase) inhibitor, administered concurrently with radiation therapy in children with newly diagnosed intrinsic diffuse brainstem glioma (BSG). Children>3 and <21 years of age with newly diagnosed nondissemi-nated intrinsic diffuse BSG were treated with concur-rent tipifarnib and radiation, followed by adjuvant tipi-farnib. Escalating doses of tipifarnib were administered orally twice daily, continuously, for the entire duration of radiation, followed by a 2-week break. Postradiation tipifarnib, 200 mg/m2/dose, was administered twice daily for 21 consecutive days, in 28-day cycles. Seven-teen patients, median age 5.9 years (range, 3.6–13.8), received external beam radiation therapy administered concurrently with tipifarnib at dose levels ranging from 100 to 150 mg/m2/dose, followed by adjuvant tipifarnib for up to 24 months in the absence of tumor progres-sion or unacceptable toxicity. Dose-limiting toxicities Phase I trial of tipifarnib in children with newly diagnosed intrinsic diffuse brainstem gliom