Phase 1 study of concurrent RMP-7 and carboplatin with radiotherapy for children with newly diagnosed brainstem gliomas

Authors

  • Roger J. Packer M.D.,

    Corresponding author
    1. Division of Neurology, Children's National Medical Center, Washington, DC
    2. Department of Neurology, The George Washington University, Washington, District of Columbia
    3. Department of Pediatrics, The George Washington University, Washington, District of Columbia
    • Division of Neurology, Children's National Medical Center; 111 Michigan Avenue, NW, Washington, DC 20010
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    • Fax: (202) 884-5226

  • Mark Krailo Ph.D.,

    1. University of Southern California, Keck School of Medicine, Los Angeles, California
    2. The Children's Oncology Group, Arcadia, California
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  • Minesh Mehta M.D.,

    1. Department of Radiation Oncology, The University of Wisconsin Medical Center, Madison, Wisconsin
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  • Katherine Warren M.D.,

    1. Division of Neuro-Oncology Branch, The National Cancer Institute, Bethesda, Maryland
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  • Jeffrey Allen M.D.,

    1. Division of Oncology, New York University, New York, New York
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  • Regina Jakacki M.D.,

    1. Division of Oncology, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania
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  • Judith G. Villablanca M.D.,

    1. Division of Oncology, Children's Hospital of Los Angeles, Los Angeles, California
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  • Akiko Chiba B.S.,

    1. Division of Hematology/Oncology, Children's National Medical Center, Washington, District of Columbia
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  • Gregory Reaman M.D.

    1. Department of Pediatrics, The George Washington University, Washington, District of Columbia
    2. The Children's Oncology Group, Arcadia, California
    3. Division of Hematology/Oncology, Children's National Medical Center, Washington, District of Columbia
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  • Presented, in part, at the 33rd Annual Meeting of the Child Neurology Society, Ottawa, Canada, October 15, 2004.

Abstract

BACKGROUND

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.

METHODS

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).

RESULTS

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.

CONCLUSIONS

The results of the current study confirmed the feasibility of giving RMP-7 and carboplatin daily during radiotherapy. Cancer 2005. © 2005 American Cancer Society.

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