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Efficacy and patient-reported outcomes with dose-intense temozolomide in patients with newly diagnosed pure and mixed anaplastic oligodendroglioma: a phase II multicenter study

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Abstract

Standard initial therapy for patients with pure and mixed anaplastic oligodendrogliomas (AO/MAO) includes chemotherapy and radiation therapy. Anaplastic oligodendrogliomas with 1p/19q co-deletion are more responsive to chemotherapy. There is concern for potential long-term CNS toxicity of radiation. Hence an approach using chemotherapy initially and reserving radiation for progressive disease is attractive. This multicenter phase II trial included patients with newly diagnosed AO/MAO with central pathology review and 1p/19q assay. Temozolomide was given 150 mg/m2 days 1–7 and 15–21, every 28 days for 8 cycles. The primary endpoint was progression free survival (PFS). Secondary endpoints included response rate, overall survival (OS), treatment toxicity and health-related quality of life (HRQL). Data from 62 patients enrolled between December 2001 and April 2007 at seven centers were analyzed. Among patients with measurable disease, 8 % achieved complete remission, 56 % had stable disease and 36 % had progression. The median PFS and OS were 27.2 months (95 % CI 11.9–36.3) and 105.8 months (95 % CI 51.5–N/A), respectively. Both 1p loss and 1p/19q co-deletion were positive prognostic factors for PFS (p < 0.001) and OS (p < 0.001); and there was some suggestion that 1p/19q co-deletion also predicted better response to chemotherapy (p = 0.007). Grade 3/4 toxicities were mainly hematological. Significantly improved HRQL in the future uncertainty domain of the brain cancer module was seen after cycle 4 (p < 0.001). This trial achieved outcomes similar to those reported previously. Toxicities from dose-intense temozolomide were manageable. Improvement in at least one HRQL domain increased over time. This trial supports the further study of first-line temozolomide monotherapy as an alternative to radiation therapy for patients with newly diagnosed AO/MAO with 1p 19q co-deleted tumors.

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Conflict of interest

Dr. Ahluwalia—Consultant or speaker for the following company: Merck & Co. Inc. Dr. Fisher—Serves on Editorial Board of the Journal of Neuro-Oncology Dr. Schiff—Travel support but no remuneration from Merck. Dr. Pannullo—Consulting for Merck & Schering Plough. Dr. Peereboom—Consultant and speaker for the following company: Merck & Co. Inc. None—Drs. Xie, Dahiya, Hashemi-Sadraei, Chamberlain, Newton, and Prayson; Ms. Brewer, Ms. Wood, and Dr. Elson.

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Authors and Affiliations

  1. Brain Tumor & Neuro-Oncology Center, Neurological Institute, Cleveland Clinic, 9500 Euclid Avenue (S70), Cleveland, OH, 44195, USA

    Manmeet S. Ahluwalia, Hao Xie, Saurabh Dahiya, Cathy Brewer, Richard Prayson & David M. Peereboom

  2. Solid Tumor Oncology, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Avenue (R35), Cleveland, OH, 44195, USA

    Manmeet S. Ahluwalia, Hao Xie, Laura Wood & David M. Peereboom

  3. Hematology-Oncology, University of Cincinnati, 231 Albert Sabin Way, Cincinnati, OH, 45267, USA

    Nooshin Hashemi-Sadraei

  4. Neuro-Oncology Center, University of Virginia, Box 800432, Charlottesville, VA, 22908, USA

    David Schiff

  5. Department of Neurology, Stanford University, 730 Welch Rd, Ste 206, Palo Alto, CA, 94304, USA

    Paul G. Fisher

  6. Department of Neurology, Fred Hutchinson Cancer Research Center, University of Washington Neuro-Oncology Program, 825 Eastlake Avenue E, MailStop G-6800, Seattle, WA, 98109, USA

    Marc C. Chamberlain

  7. Weill Cornell Brain and Spine Center, Neurological Surgery, 525 East 68th Street, New York, NY, 10065, USA

    Susan Pannullo

  8. Department of Neurology, Dardinger Neuro-Oncology Center, Ohio State University Medical Center, 465 Means Hall, 1654 Upham Drive, Columbus, OH, 43210, USA

    Herbert B. Newton

  9. Anatomic Pathology, Pathology & Laboratory Medicine Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Richard Prayson

  10. Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    Paul Elson

  11. Cleveland Clinic Lerner College of Medicine, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA

    David M. Peereboom

Authors
  1. Manmeet S. Ahluwalia
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  2. Hao Xie
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  3. Saurabh Dahiya
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  4. Nooshin Hashemi-Sadraei
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  5. David Schiff
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  7. Marc C. Chamberlain
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  8. Susan Pannullo
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  9. Herbert B. Newton
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  11. Laura Wood
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  12. Richard Prayson
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  13. Paul Elson
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  14. David M. Peereboom
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Corresponding author

Correspondence to David M. Peereboom.

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Manmeet S. Ahluwalia and Hao Xie have equally contributed to this article.

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Ahluwalia, M.S., Xie, H., Dahiya, S. et al. Efficacy and patient-reported outcomes with dose-intense temozolomide in patients with newly diagnosed pure and mixed anaplastic oligodendroglioma: a phase II multicenter study. J Neurooncol 122, 111–119 (2015). https://doi.org/10.1007/s11060-014-1684-y

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  • DOI: https://doi.org/10.1007/s11060-014-1684-y

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