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/(m(2)/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/(m(2)/day). the benefits of taxanes as clinical radiation sensitizers for children with high-grade gliomas, if any, remain to be determined.