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.


METHODS
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.
Liu
L
L
Department of Radiation Oncology, University of Pennsylvania Medical Center, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA.
Vapiwala
N
N
Munoz
L K
LK
Winick
N J
NJ
Weitman
S
S
Strauss
L C
LC
Frankel
L S
LS
Rosenthal
D I
DI
D000293:Adolescent; D001921:Brain / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D005910:Glioma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage*; D011832:Radiation Injuries / Q000517:prevention & control; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D011882:Radiotherapy, High-Energy / Q000379:methods*; D016019:Survival Analysis; D016896:Treatment Outcome
D011838:Radiation-Sensitizing Agents; D017239:Paclitaxel