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A North American brain tumor consortium (NABTC 99-04) phase II trial of temozolomide plus thalidomide for recurrent glioblastoma multiforme

  • Clinical – Patient Studies
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Background

Laboratory and clinical data suggest that the anti-angiogenic agent, thalidomide, if combined with cytotoxic agents, may be effective against recurrent glioblastoma multiforme (GBM).

Objectives

To determine 6-month progression-free survival (6PFS) and toxicity of temozolomide plus thalidomide in adults with recurrent GBM.

Patients and methods

Eligible patients had recurrent GBM after surgery, radiotherapy, and/or adjuvant chemotherapy. Temozolomide was given at 150–200 mg/m2/day on days 1–5 of each 28-day cycle. Thalidomide was given orally at 400 mg at bedtime (days 1–28) and increased to 1,200 mg as tolerated. Patients were evaluated with magnetic resonance imaging scans every 56 days. The study was designed to detect an increase of the historical 6PFS for GBM from 10 to 30%.

Results

Forty-four patients were enrolled, 43 were evaluable for efficacy and safety. The study population included 15 women, 29 men; median age was 53 years (range 32–84); median Karnofsky performance status was 80% (range 60–100%). Thirty-six (82%) patients were chemotherapy-naïve. There were 57 reports of toxicity of grade 3 or greater. Non-fatal grade 3–4 granulocytopenia occurred in 15 patients (34%). The objective response rate was 7%. The estimated probability of being progression-free at 6 months with this therapy is 24% [95% confidence interval (C.I.) 12–38%]. The median time to progression is 15 weeks (95% C.I. 10–20 weeks). There was no observed correlation between serum levels of vascular endothelial growth factor, basic fibroblast growth factor, and IL-8 and the 6PFS outcome.

Conclusion

This drug combination was reasonably safe, but with little indication of improvement compared to temozolomide alone.

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Acknowledgments

This study was supported under the following grants: CA62412, CA16672 (M.D. Groves, V.K. Puduvalli, C.A. Conrad, M.R. Gilbert, I.W. Tremont-Lukats, T-J. Liu, P. Peterson, K.R. Hess, W.K. Alfred Yung), CA62399, CA62422, M01-RR00079 (S.M. Chang, K.R. Lamborn, M.D. Prados), U01CA62407-08 (P.Y. Wen), U01CA62405, M01-RR00056 (D. Schiff), U01 CA62399, M01-RR0865 (T.F. Cloughesy), U01CA62399, M01-RR00042 (H. Greenberg), 5-U01CA62399-09 (L.E. Abrey, L.M. DeAngelis).

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Authors and Affiliations

  1. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, 1400 Holcombe, 431, Houston, TX, 77030, USA

    Morris D. Groves, Vinay K. Puduvalli, Charles A. Conrad, Mark R. Gilbert, Ivo W. Tremont-Lukats, Ta-Jen Liu, Pamela Peterson, Kenneth R. Hess & W. K. Alfred Yung

  2. The University of California, San Francisco, CA, USA

    Susan M. Chang, Kathleen R. Lamborn & Michael D. Prados

  3. The University of Pittsburg Medical Center, Pittsburg, PA, USA

    David Schiff

  4. University of California, Los Angeles, CA, USA

    Timothy F. Cloughesy

  5. Dana Farber/Brigham and Women‘s Cancer Center, Boston, MA, USA

    Patrick Y. Wen

  6. University of Michigan, Ann Arbor, MI, USA

    Harry Greenberg

  7. Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Lauren E. Abrey & Lisa M. DeAngelis

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  1. Morris D. Groves
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  2. Vinay K. Puduvalli
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  11. Patrick Y. Wen
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  15. Kenneth R. Hess
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  16. Kathleen R. Lamborn
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  18. W. K. Alfred Yung
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Corresponding author

Correspondence to Morris D. Groves.

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Groves, M.D., Puduvalli, V.K., Chang, S.M. et al. A North American brain tumor consortium (NABTC 99-04) phase II trial of temozolomide plus thalidomide for recurrent glioblastoma multiforme. J Neurooncol 81, 271–277 (2007). https://doi.org/10.1007/s11060-006-9225-y

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  • DOI: https://doi.org/10.1007/s11060-006-9225-y

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