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

Abstract

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.

• Authors: L Liu, N Vapiwala, L K Munoz, N J Winick, S Weitman, L C Strauss, L S Frankel, D I Rosenthal
• Journal: Medical and pediatric oncology (Med Pediatr Oncol) Vol. 37 Issue 4 Pg. 390-2 (Oct 2001) ISSN: 0098-1532 [Print] United States
• PMID: 11568904 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• Radiation-Sensitizing Agents
• Paclitaxel

Topics

• Adolescent
• Brain (radiation effects)
• Brain Neoplasms (drug therapy, mortality, pathology, radiotherapy)
• Child
• Child, Preschool
• Combined Modality Therapy
• Drug Administration Schedule
• Female
• Follow-Up Studies
• Glioblastoma (drug therapy, mortality, pathology, radiotherapy)
• Glioma (drug therapy, mortality, pathology, radiotherapy)
• Humans
• Infusions, Intravenous
• Male
• Paclitaxel (administration & dosage)
• Radiation Injuries (prevention & control)
• Radiation-Sensitizing Agents (administration & dosage)
• Radiotherapy, High-Energy (methods)
• Survival Analysis
• Treatment Outcome