Phase II evaluation of topotecan for pediatric central nervous system tumors.

Abstract

BACKGROUND:

Topotecan is a topoisomerase I inhibitor that has good penetration across the blood-brain barrier and significant antitumor activity against human brain tumor xenografts. In a Phase I trial in children with refractory cancer, topotecan was well tolerated when administered as a 24-hour infusion. The maximum tolerated dose was 5.5 mg/m2 and the dose-limiting toxicity was myelosuppression. This Phase II study of topotecan was performed to assess the activity of topotecan against childhood brain tumors.

METHODS:

Forty-five children with either a previously treated primary brain tumor that was refractory to standard therapy, or an untreated brain stem glioma or glioblastoma multiforme, received topotecan administered as a 24-hour intravenous infusion every 21 days. The initial dose was 5.5 mg/m2 with escalation to 7.5 mg/m2 on the second and subsequent doses in patients who did not experience dose-limiting toxicity.

RESULTS:

There were no complete or partial responses in the patients with high grade glioma (n=9), medulloblastoma (n=9), or brain stem glioma (n=14). One of 2 patients with a low grade glioma had a partial response lasting more than 17 months; 3 patients with a brain stem glioma had stable disease for 12 to 28 weeks; and 1 patient with a malignant neuroepithelial tumor and 1 patient with an optic glioma had stable disease for 41 weeks and 22 weeks, respectively. Dose escalation from 5.5 mg/m2 to 7.5 mg/m2 was well tolerated in the first 11 patients enrolled on this study who had not received prior craniospinal radiation therapy. The starting dose was subsequently increased to 7.5 mg/m2 for patients without prior craniospinal radiation.

CONCLUSIONS:

Topotecan administered as a 24-hour infusion every 21 days is inactive in high grade gliomas, medulloblastomas, and brain stem tumors.

• Authors: S M Blaney, P C Phillips, R J Packer, R L Heideman, S L Berg, P C Adamson, J C Allen, S E Sallan, R I Jakacki, B J Lange, G H Reaman, M E Horowitz, D G Poplack, F M Balis
• Journal: Cancer (Cancer) Vol. 78 Issue 3 Pg. 527-31 (Aug 01 1996) ISSN: 0008-543X [Print] United States
• PMID: 8697400 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article)

Chemical References

• Antineoplastic Agents
• Topotecan
• Camptothecin

Topics

• Adolescent
• Adult
• Antineoplastic Agents (administration & dosage, adverse effects, therapeutic use)
• Brain Neoplasms (drug therapy)
• Brain Stem
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Child
• Child, Preschool
• Drug Administration Schedule
• Female
• Glioblastoma (drug therapy)
• Glioma (drug therapy)
• Humans
• Infant
• Infusions, Intravenous
• Male
• Topotecan