PHASE-II EVALUATION OF TOPOTECAN FOR PEDIATRIC CENTRAL-NERVOUS-SYSTEMTUMORS

Citation
Sm. Blaney et al., PHASE-II EVALUATION OF TOPOTECAN FOR PEDIATRIC CENTRAL-NERVOUS-SYSTEMTUMORS, Cancer, 78(3), 1996, pp. 527-531
Citations number
17
Categorie Soggetti
Oncology
Journal title
CancerACNP
ISSN journal
0008543X
Volume
78
Issue
3
Year of publication
1996
Pages
527 - 531
Database
ISI
SICI code
0008-543X(1996)78:3<527:PEOTFP>2.0.ZU;2-E
Abstract
BACKGROUND. Topotecan is a topoisomerase I inhibitor that has good pen etration across the blood-brain barrier and significant antitumor acti vity against human brain tumor xenografts. In a Phase I trial in child ren with refractory cancer, topotecan was well tolerated when administ ered as a 24-hour infusion. The maximum tolerated dose was 5.5 mg/m(2) and the dose-limiting toxicity was myelosuppression. This Phase II st udy of topotecan was performed to assess the activity of topotecan aga inst childhood brain tumors. METHODS, Forty-five children with either a previously treated primary brain tumor that was refractory to standa rd therapy, or an untreated brain stem glioma or glioblastoma multifor me, received topotecan administered as a 24-hour intravenous infusion every 21 days. The initial dose was 5.5 mg/m(2) with escalation to 7.5 mg/m(2) on the second and subsequent doses in patients who did not ex perience dose-limiting toxicity. RESULTS, There were no complete or pa rtial responses in the patients with high grade glioma (n = 9), medull oblastoma (n = 9), or brain stem glioma (n = 14). One of 2 patients wi th a low grade glioma had a partial response lasting more than 17 mont hs; 3 patients with a brain stem glioma had stable disease for 12 to 2 8 weeks; and 1 patient with a malignant neuroepithelial tumor and 1 pa tient with an optic glioma had stable disease for 41 weeks and 22 week s, respectively. Dose escalation from 5.5 mg/m(2) to 7.5 mg/m(2) was w ell tolerated in the first 11 patients enrolled on this study who had not received prior craniospinal radiation therapy. The starting dose w as subsequently increased to 7.5 mg/m(2) for patients without prior cr aniospinal radiation. CONCLUSIONS, Topotecan administered as a 24-hour infusion every 21 days is inactive in high grade gliomas, medulloblas tomas, and brain stem tumors. (C) 1996 American Cancer Society.