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BCNU wafer placement with temozolomide (TMZ) in the immediate postoperative period after tumor resection followed by radiation therapy with TMZ in patients with newly diagnosed high grade glioma: final results of a prospective, multi-institutional, phase II trial

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Abstract

Temozolomide (TMZ) and BCNU have demonstrated anti-glioma synergism in preclinical models. We report final data from a prospective, multi-institutional study of BCNU wafers and early TMZ followed by radiation therapy with TMZ in patients with newly diagnosed malignant glioma. 65 patients were consented in 4 institutions, and 46 patients (43 GBM, 3 AA) were eligible for analysis. After resection and BCNU wafer placement, TMZ began on day four postoperatively. Radiation and TMZ (RT/TMZ) were then administered, followed by monthly TMZ at 200 mg/m2 for the first 26 patients, which was reduced to 150 mg/m2 for the remaining 20 patients. Non-hematologic toxicities were minimal. Nine of 27 patients (33 %) who received 200 mg/m2 TMZ, but only 1 of 20 (5 %) who received 150 mg/m2, experienced grade 3/4 thrombocytopenia. Median progression free survival (PFS) and overall survival (OS) period was 8.5 and 18 months, respectively. The 1-year OS rate was 76 %, which is a significant improvement compared with the historical control 1-year OS rate of 59 % (p = 0.023). However, there was no difference in 1-year OS compared with standard RT/TMZ (p = 0.12) or BCNU wafer followed by RT/TMZ (p = 0.87) in post hoc analyses. Early post-operative TMZ can be safely administered with BCNU wafers following resection of malignant glioma at the 150 mg/m2 dose level. Although there was an OS benefit compared to historical control, there was no indication of benefit for BCNU wafers and early TMZ in addition to standard RT/TMZ or early TMZ in addition to regimens of BCNU wafers followed by RT/TMZ.

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Conflict of interest

Dr. Anthony Asher is a consultant for Medtronic Corporation, Baxano, Hyperbranch Medical Technologies, and Ethicon. None of the other authors have potential conflicts of interest to declare.

Funding

This study was funded by Guilford Pharmaceuticals, Inc., which is now affiliated with Eisai, Incorporated.

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Authors and Affiliations

  1. Southeast Radiation Oncology Group, Department of Radiation Oncology, Levine Cancer Institute at Carolinas Medical Center, 1021 Morehead Medical Drive, Charlotte, NC, 28204, USA

    Stuart H. Burri & Roshan S. Prabhu

  2. Department of Oncology, Levine Cancer Institute, Charlotte, NC, USA

    Ashley L. Sumrall & Wendy Brick

  3. Carolina Neurosurgery and Spine Associates, Charlotte, NC, USA

    Brian D. Blaker, Brent E. Heideman Jr., Peggy Boltes & Walter F. Wiggins

  4. Brain Tumor Fund for the Carolinas, Charlotte, NC, USA

    Renee Kelly

  5. Department of Cancer Biostatistics, Levine Cancer Institute, Charlotte, NC, USA

    James T. Symanowski

  6. Department of Neuro-oncology, Barrow Neurological Institute, Phoenix, AZ, USA

    Lynn Ashby

  7. Department of Biostatistics, Carolinas Medical Center, Charlotte, NC, USA

    H. James Norton

  8. Department of Neurosurgery, Thomas Jefferson University, Philadelphia, PA, USA

    Kevin Judy

  9. Carolina Neurosurgery and Spine Associates, Neuroscience Institute, Carolinas Healthcare System, Levine Cancer Institute, Charlotte, NC, USA

    Anthony L. Asher

Authors
  1. Stuart H. Burri
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  11. Lynn Ashby
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Corresponding author

Correspondence to Stuart H. Burri.

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Supplementary material 1 (DOCX 23 kb)

Supplemental Fig. 1

Progression free survival in all patients (n = 46). Longest follow-up time was 68.3 months; plot truncated at 36 months. Supplementary material 2 (DOCX 60 kb)

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Burri, S.H., Prabhu, R.S., Sumrall, A.L. et al. BCNU wafer placement with temozolomide (TMZ) in the immediate postoperative period after tumor resection followed by radiation therapy with TMZ in patients with newly diagnosed high grade glioma: final results of a prospective, multi-institutional, phase II trial. J Neurooncol 123, 259–266 (2015). https://doi.org/10.1007/s11060-015-1793-2

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