A Phase I study of concurrent RMP-7 and carboplatin with radiation therapy 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, DC
    3. Department of Pediatrics, The George Washington University, Washington, DC
    • Center for Neuroscience and Behavioral Medicine, Department 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. The National Cancer Institute, Bethesda, Maryland
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  • Jeffrey Allen M.D.,

    1. Department of Neurology and Pediatrics, New York University, New York, New York
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  • Regina Jakacki M.D.,

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

    1. Department of Pediatrics, 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, DC
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  • Gregory Reaman M.D.

    1. Department of Pediatrics, The George Washington University, Washington, DC
    2. The Children's Oncology Group, Arcadia, California
    3. Division of Hematology/Oncology, Children's National Medical Center, Washington, DC
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  • Presented in part at 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 to these children, and a potential way to improve its efficacy is to add radiosensitizers. Carboplatin is antineoplastic and radiosensitizing; however, its 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 objective of this Phase I study was to determine the toxicity and feasibility of delivering RMP-7 and carboplatin for 5 successive days during radiotherapy to children with newly diagnosed, diffuse, intrinsic brainstem gliomas.

METHODS

RMP-7 was given prior to the end of carboplatin infusion. Local radiotherapy, in dose fractions of 180 centigrays (cGy) per day (to a total dose of 5940 cGy), was given within 4 hours of completion of drug delivery. Duration of treatment was escalated in a stepwise, weekly fashion in cohorts of 3 patients, until there was treatment-limiting toxicity or until radiotherapy was completed. Thirteen patients were treated, and their median age was 7 years (age range, 3–12 yrs).

RESULTS

One child died early during treatment of progressive disease and was not assessable for toxicity. Treatment for 3 weeks, 4 weeks, and 5 weeks was tolerated well, with mild flushing, tachycardia, nausea, emesis, dizziness, and abdominal pain. One of 3 children treated at the full duration of therapy (33 doses over 7 weeks) developed dose-limiting hepatotoxicity and neutropenia. The estimated median survival was 328 days, and 1 patient remained free of disease progression for > 400 days after the initiation of treatment.

CONCLUSIONS

The results of this study confirmed the feasibility of giving RMP-7 and carboplatin daily during radiotherapy to children with brainstem tumors. Cancer 2005. © 2005 American Cancer Society.

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