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Phase 1 study of concurrent RMP-7 and carboplatin with radiotherapy for children with newly diagnosed brainstem gliomas†
Article first published online: 2 AUG 2005
Copyright © 2005 American Cancer Society
Volume 104, Issue 6, pages 1281–1287, 15 September 2005
How to Cite
Packer, R. J., Krailo, M., Mehta, M., Warren, K., Allen, J., Jakacki, R., Villablanca, J. G., Chiba, A. and Reaman, G. (2005), Phase 1 study of concurrent RMP-7 and carboplatin with radiotherapy for children with newly diagnosed brainstem gliomas. Cancer, 104: 1281–1287. doi: 10.1002/cncr.21301
Presented, in part, at the 33rd Annual Meeting of the Child Neurology Society, Ottawa, Canada, October 15, 2004.
- Issue published online: 31 AUG 2005
- Article first published online: 2 AUG 2005
- Manuscript Accepted: 25 MAR 2005
- Manuscript Revised: 22 FEB 2005
- Manuscript Received: 29 NOV 2004
- brainstem glioma;
Ninety percent of children with diffuse intrinsic brainstem tumors will die within 18 months of diagnosis. Radiotherapy is of transient benefit, and one way to potentially improve its efficacy is to add radiosensitizers. Carboplatin is antineoplastic and radiosensitizing. However, delivery to the primary tumor site is problematic. RMP-7 is a bradykinin analog that causes selective permeability of the blood-brain-tumor interface. The goal of the current Phase I study was to determine the toxicity and feasibility of delivering RMP-7 and carboplatin for 5 successive days during radiotherapy.
RMP-7 was given before the end of carboplatin infusion. Local radiotherapy (5940 centigrays) was given within 4 hours of completion of drug delivery. Duration of treatment was escalated in a stepwise, weekly fashion, in cohorts of 3, until there was treatment-limiting toxicity or until radiotherapy was completed. Thirteen patients were treated, whose median age was 7 years (range, 3–14 yrs).
One child died early in treatment of progressive disease and was not assessable for toxicity. Treatment for 3, 4, or 5 weeks was tolerated well, with mild flushing, tachycardia, nausea, emesis, dizziness, and abdominal pain. Of 3 children treated at the full duration of therapy (33 doses over 7 wks), 1 developed dose-limiting hepatotoxicity and neutropenia. The estimated median survival period was 328 days, and 1 patient remained disease progression free > 400 days from initiation of treatment.
The results of the current study confirmed the feasibility of giving RMP-7 and carboplatin daily during radiotherapy. Cancer 2005. © 2005 American Cancer Society.