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Phase II study of fixed dose rate gemcitabine as radiosensitizer for newly diagnosed glioblastoma multiforme

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Abstract

Purpose

In order to evaluate the activity of gemcitabine as radiosensitizer for newly diagnosed glioblastoma multiforme (GBM), a prospective single-center phase II study was conducted.

Methods

Eligible patients were required to have histologically proven GBM with evaluable and/or measurable disease after surgery. They were treated by standard cranial irradiation plus concomitant fixed dose rate gemcitabine given intravenously at 175 mg/m2 weekly for 6 weeks. After chemo-radiotherapy, irrespective of tumor response, patients went on to receive oral temozolomide at 150–200 mg/m2 for 5 days every 28 days.

Results

Twenty-three patients were enrolled. Median age was 57 years (range 43–72) and median Karnofsky performance status was 90 (range 70–100). Seventeen patients had received subtotal resection of the tumor, while six patients had biopsied-only tumors. Four patients responded to treatment (17.5%) with additional 14 (61%) experiencing stable disease for an overall disease control rate of 78.5%. Median progression-free and overall survival were 6.8 and 10.1 months, respectively. The concomitant radiotherapy–gemcitabine combination was well tolerated and severe adverse events were rare, consisting of grade 3 neutropenia and hypertransaminasemia in two cases each. Twenty patients were assessable for methylguanine methyltransferase (MGMT) promoter methylation, 11 of which were found methylated. In the methylated and unmethylated cohorts, disease control was obtained in 10/11 patients (91%) and 7/9 patients (77.5%), respectively.

Conclusions

Concomitant radiotherapy–gemcitabine is active and well tolerated in newly diagnosed glioblastoma multiforme. Activity is observed both in tumors with methylated and unmethylated MGMT promoter.

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Conflict of interest statement

The authors report no conflict of interest.

Author information

Authors and Affiliations

  1. Division of Medical Oncology, Regina Elena Cancer Institute, Via Elio Chianesi, 53, 00144, Rome, Italy

    Giulio Metro, Alessandra Fabi, Michelangelo Russillo, Domenica Pellegrini & Francesco Cognetti

  2. Division of Radiotherapy, Regina Elena Cancer Institute, Rome, Italy

    Maria A. Mirri

  3. Diagnostic Imaging, Regina Elena Cancer Institute, Rome, Italy

    Antonello Vidiri

  4. Division of Neurology, Regina Elena Cancer Institute, Rome, Italy

    Andrea Pace & Marta Maschio

  5. Division of Neurosurgery, Regina Elena Cancer Institute, Rome, Italy

    Alfredo Pompili & Carmine M. Carapella

  6. Department of Pathology, Regina Elena Cancer Institute, Rome, Italy

    Mariantonia Carosi

  7. Biostatistics, Regina Elena Cancer Institute, Rome, Italy

    Diana Giannarelli

Authors
  1. Giulio Metro
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  2. Alessandra Fabi
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  3. Maria A. Mirri
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  4. Antonello Vidiri
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  5. Andrea Pace
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  6. Mariantonia Carosi
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  7. Michelangelo Russillo
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  8. Marta Maschio
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  9. Diana Giannarelli
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  10. Domenica Pellegrini
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  11. Alfredo Pompili
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  12. Francesco Cognetti
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  13. Carmine M. Carapella
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Corresponding author

Correspondence to Alessandra Fabi.

Additional information

G. Metro and A. Fabi contributed equally to this work.

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Metro, G., Fabi, A., Mirri, M.A. et al. Phase II study of fixed dose rate gemcitabine as radiosensitizer for newly diagnosed glioblastoma multiforme. Cancer Chemother Pharmacol 65, 391–397 (2010). https://doi.org/10.1007/s00280-009-1155-x

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  • DOI: https://doi.org/10.1007/s00280-009-1155-x

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