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A phase II study of feasibility and toxicity of bevacizumab in combination with temozolomide in patients with recurrent glioblastoma

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Abstract

Purpose

The aim of this prospective and multicentric phase II study was to evaluate the efficacy and safety of temozolomide (TMZ) and bevacizumab (BV) in patients (pts) with recurrent glioblastoma (GB), previously treated with chemoradiotherapy and at least three cycles of adjuvant TMZ.

Patients and methods

Patients with GB at first relapse received BV 10 mg/kg day every 2 weeks and TMZ 150 mg/m2 days 1–7 and 15–21, every 28 days. Patients underwent brain magnetic resonance imaging every 8 weeks.

Results

Thirty-two evaluable pts were recruited in 8 sites. Fourteen pts (44 %) had gross total resection. O6-methylguanine-DNA methyltransferase (MGMT) promoter was methylated in 12 pts, unmethylated in 6 pts, and missing in 14 pts. The estimated 6-month progression free survival (PFS) rate was 21.9 % (95 % CI 9.3–40.0 %). The median PFS and overall survival (OS) were 4.2 months (95 % CI 3.6–5.4 months) and 7.3 months (95 % CI 5.8–8.8 months), respectively. No significant association with MGMT status was found in terms of OS or PFS. Six of 32 pts (19 %; 95 % CI 7.2–36.4) were long-term survivors, with a median PFS and OS (50 % events) of 9.5 months (95 % CI 7.9–23.6) and 15.4 (95 % CI 8.9–NA), respectively: no differences in baseline characteristics were identified in comparison with total population. No unexpected toxicities or treatment-related deaths were observed.

Conclusions

This regimen showed to be feasible and well tolerated in pts with recurrent GB pretreated with TMZ. Further investigation is warranted to identify subpopulations that are more likely to benefit from addition of BV to GB therapy.

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Acknowledgments

Financial support for this research was provided by Roche Farma, S.A. Jesús González, MD (Pivotal CRO) provided advice for writing and submitting this paper.

Conflict of interest

Carmen Balañá has received honoraria from Roche, Merck Serono, and Novartis for lectures and advisory boards. Gaspar Reynés has received honoraria from Roche and Merck (previously Schering Plough) for lectures and advisory boards.

Ethical standards

The study was performed after approval by the Independent Ethics Committee of each site and in accordance with the Declaration of Helsinki, the Good Clinical Practices, and local ethical and legal requirements (Spanish laws). Before study entry, all patients provided written informed consent according to local ethical committee regulations.

Author information

Authors and Affiliations

  1. Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain

    J. M. Sepúlveda

  2. Medical Oncology Department, Hospital Madrid Norte Sanchinarro, Madrid, Spain

    C. Belda-Iniesta

  3. Neuro-Oncology Unit, Institut Català d’Oncologia, Bellvitge, L’Hospitalet, Spain

    M. Gil-Gil

  4. Medical Oncology Department, Hospital Clínico San Carlos, Madrid, Spain

    P. Pérez-Segura

  5. Medical Oncology Department, Consorcio Hospital General Universitario, Valencia, Spain

    A. Berrocal

  6. Medical Oncology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain

    G. Reynés

  7. Medical Oncology Department, Hospital De Sant Pau, Barcelona, Spain

    O. Gallego

  8. Radiology Department, Hospital del Mar, Barcelona, Spain

    J. Capellades

  9. Roche Farma SA, Madrid, Spain

    J. M. Ordoñez & B. La Orden

  10. Medical Oncology Department, Hospital Germans Trias i Pujol, Institut Catala d’Oncologia (ICO), Carretera Canyet sn, 08916, Badalona, Barcelona, Spain

    C. Balañá

Authors
  1. J. M. Sepúlveda
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  2. C. Belda-Iniesta
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  3. M. Gil-Gil
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  4. P. Pérez-Segura
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  6. G. Reynés
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  7. O. Gallego
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  8. J. Capellades
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  9. J. M. Ordoñez
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  10. B. La Orden
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  11. C. Balañá
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Corresponding author

Correspondence to C. Balañá.

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Sepúlveda, J.M., Belda-Iniesta, C., Gil-Gil, M. et al. A phase II study of feasibility and toxicity of bevacizumab in combination with temozolomide in patients with recurrent glioblastoma. Clin Transl Oncol 17, 743–750 (2015). https://doi.org/10.1007/s12094-015-1304-0

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  • DOI: https://doi.org/10.1007/s12094-015-1304-0

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