Phase 2 study of carboplatin, irinotecan, and bevacizumab for recurrent glioblastoma after progression on bevacizumab therapy

Authors

  • David A. Reardon MD,

    Corresponding author
    1. Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
    2. Department of Pediatrics, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
    • The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Box 3624, Durham, NC 27710
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    • Fax: (919) 668-2485

  • Annick Desjardins MD,

    1. Department of Medicine, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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  • Katherine B. Peters MD, PhD,

    1. Department of Medicine, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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  • James J. Vredenburgh MD,

    1. Department of Medicine, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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  • Sridharan Gururangan MD,

    1. Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
    2. Department of Pediatrics, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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  • John H. Sampson MD,

    1. Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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  • Roger E. McLendon MD,

    1. Department of Pathology, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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  • James E. Herndon II PhD,

    1. Department of Cancer Center Biostatistics, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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  • April Coan MS,

    1. Department of Cancer Center Biostatistics, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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  • Stevie Threatt BS,

    1. Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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  • Allan H. Friedman MD,

    1. Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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  • Henry S. Friedman MD

    1. Department of Surgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
    2. Department of Pediatrics, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina
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Abstract

BACKGROUND:

The efficacy of carboplatin, irinotecan, and bevacizumab among recurrent glioblastoma (GBM) patients after prior progression on bevacizumab therapy in a phase 2, open-label, single-arm trial was evaluated.

METHODS:

Eligible patients received carboplatin (area under the plasma curve [AUC] 4 mg/ml-min) on day 1, whereas bevacizumab (10 mg/kg) and irinotecan (340 mg/m2 for patients on CYP3A enzyme-inducing anti-epileptics [EIAEDs] and 125 mg/m2 for patients not on EIAEDs) were administered on days 1 and 14 of every 28-day cycle. Patients were evaluated after each of the first 2 cycles and then after every other cycle. Treatment continued until progressive disease, unacceptable toxicity, noncompliance, or voluntary withdrawal. The primary end point was progression-free survival at 6 months (PFS-6), and secondary end points included safety and median overall survival (OS).

RESULTS:

All patients had progression on at least 1 prior bevacizumab regimen and 56% enrolled after either second or third overall progression. The median OS was 5.8 months (95% confidence interval [CI], 4.0-7.0 months) and PFS-6 rate was 16% (95% CI, 5.0%-32.5%). The most common grade 3 or 4 events were hematologic and occurred in 29% of cycles. Nine patients (38%) required dose modification. There were no treatment-related deaths.

CONCLUSIONS:

Carboplatin, irinotecan, and bevacizumab was associated with modest activity and adequate safety among recurrent GBM patients who progressed on bevacizumab previously. Cancer 2011;. © 2011 American Cancer Society.

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