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Phase II trial of erlotinib with temozolomide and radiation in patients with newly diagnosed glioblastoma multiforme

  • Clinical Study - Patient Study
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Abstract

Approximately 40–50% of glioblastomas (GBM) overexpress epidermal growth factor receptor (EGFR). Erlotinib is a specific and potent EGFR tyrosine kinase inhibitor active against refractory GBM. Patients with non-small cell lung cancer and ≥grade 2 erlotinib-induced rash have improved survival. This phase 2 study assessed the efficacy and safety of concurrent radiation therapy (RT) and temozolomide with pharmacodynamic dose escalation of erlotinib in patients with newly diagnosed GBM. Patients received RT 60 Gy in 30 fractions with concurrent temozolomide 75 mg/m2/day × 42 days, followed in four weeks by temozolomide 150–200 mg/m2/day × 5, every 28 days for 12 cycles. Patients received erlotinib, 50 mg/day and increased by 50 mg/day every 2 weeks until the occurrence of grade 2 rash or to a maximum dose of 150 mg/day, from day 1 until disease progression. Twenty-seven patients were treated in this study. Twenty-two (81%) patients came off study for progressive disease (18 [67%]) or adverse events (4 [15%]). Eighteen patients (67%) have died. Median progression-free survival was 2.8 months, and the median overall survival was 8.6 months. Five patients remain on study with a median follow-up of 16 months. Grade 3/4 toxicities included thrombocytopenia, anemia, lymphopenia, fatigue, and febrile neutropenia. There were four deaths on study, three definitely treatment-related; therefore, the trial was terminated after accrual of 27 of 30 planned patients. Erlotinib co administered with RT and temozolomide was not efficacious and had an unacceptable toxicity.

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Authors and Affiliations

  1. Brain Tumor and Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    David M. Peereboom, Manmeet S. Ahluwalia, Cathy J. Brewer, Neeraj Agarwal, Glen H. J. Stevens, John H. Suh, Michael A. Vogelbaum, Robert J. Weil & Gene H. Barnett

  2. Solid Tumor Oncology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    Dale R. Shepard

  3. Radiation Oncology, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    John H. Suh

  4. Neurosurgery, Geisinger Health System, Danville, PA, USA

    Steven A. Toms

  5. Quantitative Health Services, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, USA

    Paul Elson

Authors
  1. David M. Peereboom
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  2. Dale R. Shepard
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  3. Manmeet S. Ahluwalia
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  9. Michael A. Vogelbaum
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Correspondence to David M. Peereboom.

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Peereboom, D.M., Shepard, D.R., Ahluwalia, M.S. et al. Phase II trial of erlotinib with temozolomide and radiation in patients with newly diagnosed glioblastoma multiforme. J Neurooncol 98, 93–99 (2010). https://doi.org/10.1007/s11060-009-0067-2

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  • DOI: https://doi.org/10.1007/s11060-009-0067-2

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