A phase I study of cranial radiation therapy with concomitant continuous infusion paclitaxel in children with brain tumors

Background. The prognosis of children with high-grade astrocytomas of the central nervous system is grim and has not been substantially improved by conventional chemoradiotherapy. We performed a multi-institutional phase I study to determine the toxicities and tolerance of concurrent external beam radiation of the brain and a unique dose-schedule of paclitaxel as a radiation sensitizer. Procedure. Paclitaxel was delivered intravenously as a continuous 24 h/ day, 7 days/week infusion during the entire 6-week course of fixed schedule standard radiation therapy. The dose of paclitaxel was escalated in patient cohorts in standard phase I design. Results. Eleven patients (eight brain stem gliomas, one glioblastoma multiforme, and two gliomatosis cerebri) were treated, Dose-limiting toxicity was encountered in the two patients treated at 6 mg/(m²/24 h), both of whom developed severe obstipation requiring prolonged hospitalization. Conclusions. We have shown in this first study of its kind that paclitaxel can be administered safely to children as a 6-week continuous infusion concurrent with cranial irradiation. The maximally tolerated and recommended phase II dose is 4 mg/ (m²/day). The benefits of taxanes as clinical radiation sensitizers for children with high-grade gliomas, if any, remain to be determined.