Phase II trial of irinotecan plus celecoxib in adults with recurrent malignant glioma

Authors

  • David A. Reardon M.D.,

    Corresponding author
    1. Department of Surgery, Duke University Medical Center, Durham, North Carolina
    2. Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
    • The Brain Tumor Center at Duke, 047 Baker House, Box 3624, Duke University Medical Center, Durham, NC 27710
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    • Fax: (919) 681-1697

  • Jennifer A. Quinn M.D.,

    1. Department of Surgery, Duke University Medical Center, Durham, North Carolina
    2. Department of Medicine, Duke University Medical Center, Durham, North Carolina
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  • James Vredenburgh M.D.,

    1. Department of Medicine, Duke University Medical Center, Durham, North Carolina
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  • Jeremy N. Rich M.D.,

    1. Department of Surgery, Duke University Medical Center, Durham, North Carolina
    2. Department of Medicine, Duke University Medical Center, Durham, North Carolina
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  • Sridharan Gururangan M.D.,

    1. Department of Surgery, Duke University Medical Center, Durham, North Carolina
    2. Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
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  • Michael Badruddoja M.D.,

    1. Department of Surgery, Duke University Medical Center, Durham, North Carolina
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  • James E. Herndon II Ph.D.,

    1. Department of Cancer Center Biostatistics, Duke University Medical Center, Durham, North Carolina
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  • Jeannette M. Dowell M.Sci.,

    1. Department of Cancer Center Biostatistics, Duke University Medical Center, Durham, North Carolina
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  • Allan H. Friedman M.D.,

    1. Department of Surgery, Duke University Medical Center, Durham, North Carolina
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  • Henry S. Friedman M.D.

    1. Department of Surgery, Duke University Medical Center, Durham, North Carolina
    2. Department of Pediatrics, Duke University Medical Center, Durham, North Carolina
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Abstract

BACKGROUND

In the current study, the authors report a Phase II trial of irinotecan (CPT-11), a topoisomerase I inhibitor active against malignant glioma (MG), with celecoxib, a selective COX-2 inhibitor, among MG patients with recurrent disease.

METHODS

Patients with MG at any type of recurrence received CPT-11, administered as a 90-minute intravenous infusion on Weeks 1, 2, 4, and 5 of each 6-week cycle plus celecoxib, which was administered continuously at a dose of 400 mg twice a day. CPT-11 was given at a dose of 350 mg/m2 for patients receiving enzyme-inducing antiepileptic drugs (EIAEDs) and at a dose of 125 mg/m2 for those patients not receiving EIAEDs. Assessments were performed after every cycle. The primary endpoint was radiographic response and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and therapeutic safety.

RESULTS

Thirty-four of the 37 patients enrolled in the current study (92%) were diagnosed with recurrent GBM and 3 patients (8%) were diagnosed with recurrent anaplastic astrocytoma (AA). Twenty-one patients were receiving EIAEDs and 16 patients were not. The median follow-up time was 76.9 weeks. Concomitant CPT-11 plus celecoxib was found to be well tolerated and safe. Hematologic toxicities of ≥ Grade 3 (according the second version of the Common Toxicity Criteria of the National Cancer Institute) reportedly complicated 8.6% of treatment courses. Grade 3 diarrhea, the most commonly reported nonhematologic toxicity, occurred with equal frequency (8%), regardless of whether the patient was receiving EIAED. Six patients (16%), all whom were diagnosed with recurrent GBM, achieved an objective radiographic response whereas an additional 13 patients (35%) achieved stable disease. The median PFS was 11.0 weeks and the 6-month PFS was reported to be 25.1%. The median OS was 31.5 weeks.

CONCLUSIONS

The results of the current study confirm that CPT-11 plus celecoxib can be safely administered concurrently at full dose levels, and that this regimen has encouraging activity among heavily pretreated patients with recurrent MG. Cancer 2005. © 2005 American Cancer Society.

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