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Clinical and Translational Oncology

, Volume 21, Issue 10, pp 1364–1373 | Cite as

A comprehensive analysis of factors related to carmustine/bevacizumab response in recurrent glioblastoma

  • A. F. CardonaEmail author
  • L. Rojas
  • B. Wills
  • A. Ruiz-Patiño
  • L. Abril
  • F. Hakim
  • E. Jiménez
  • N. Useche
  • S. Bermúdez
  • J. A. Mejía
  • J. F. Ramón
  • H. Carranza
  • C. Vargas
  • J. Otero
  • P. Archila
  • J. Rodríguez
  • J. Rodríguez
  • J. Behaine
  • D. González
  • J. Jacobo
  • H. Cifuentes
  • O. Feo
  • P. Penagos
  • D. Pineda
  • L. Ricaurte
  • L. E. Pino
  • C. Vargas
  • J. C. Marquez
  • M. I. Mantilla
  • L. D. Ortiz
  • C. Balaña
  • R. Rosell
  • Z. L. Zatarain-Barrón
  • O. Arrieta
Research Article
  • 224 Downloads

Abstract

Purpose

Patients with recurrent glioblastoma (rGBM) have a poor prognosis, with survival ranging from 25 to 40 weeks. Antiangiogenic agents are widely used, showing a variable response. In this study, we explored the efficacy of carmustine plus bevacizumab (BCNU/Bev) for treating rGBM.

Methods/patients

In this study, we assessed 59 adult patients with histologically confirmed rGBM who were treated with BCNU/Bev as second-line regimen. The response rate (RR), progression-free survival (PFS) and overall survival (OS) were evaluated according to their molecular expression profile, including CD133 mRNA expression, MGMT methylation (pMGMT), PDGFR amplification, YKL40 mRNA expression, IDH1/2 condition, p53 and EGFRvIII mutation status.

Results

Median follow-up was 18.6 months, overall RR to the combination was 56.3%, and median PFS was 9.0 months (95% CI 8.0–9.9). OS from time of diagnosis was 21.0 months (95% CI 13.2–28.7) and from starting BCNU/Bev it was 10.7 months (95% CI 9.5–11.8). IDH1/2 mutations were found in 30.5% of the patients, pMGMT in 55.9% and high CD133 mRNA expression in 57.6%. Factors which positively affected PFS included performance status (p = 0.015), IDH+ (p = 0.05), CD133 mRNA expression (p = 0.009) and pMGMT+ (p = 0.007). OS was positively affected by pMGMT+ (p = 0.05). Meanwhile, YKL40 negatively affected PFS (p = 0.01) and OS (p = 0.0001). Grade ≥ 3 toxicities included hypertension (22%) and fatigue (12%).

Conclusions

BCNU/Bev is a safe and tolerable treatment for rGBM. Patients with MGMT+/IDH+ derive the greatest benefit from the treatment combination in the second-line setting. Nonetheless, high YKL40 expression discourages the use of antiangiogenic therapy.

Keywords

Glioblastoma Second-line therapy Bevacizumab Molecular expression classification 

Notes

Acknowledgements

The authors are grateful for the generous contribution from the Silberman and Buendía families, who altruistically promoted the development of cancer research in Colombia.

Funding

Supported by the Foundation for Clinical and Applied Cancer Research-FICMAC (Bogotá Colombia) research Grant 014-2012.

Compliance with ethical standards

Conflict of interest

The authors declare that there is no conflict of interest.

Ethical approval

The study was approved by the Ethics Committee and Institutional Review Board of the Clínica del Country (IRB-CC, Clínica del Country IT2010009781) following the ethical guidelines of the Helsiki Declaration (as revised in Tokio 2004).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

12094_2019_2066_MOESM1_ESM.png (120 kb)
Supplementary material 1 Overall survival (S-1A) and progression-free survival (S-1B) according to primary or secondary GBM (PNG 119 kb)
12094_2019_2066_MOESM2_ESM.png (109 kb)
Supplementary material 2 Overall survival (S-2A) and progression-free survival (S-2B) according to the combination of two of the assessed biomarkers: IDH and MGMT (PNG 109 kb)
12094_2019_2066_MOESM3_ESM.docx (2.7 mb)
Supplementary material 3 (DOCX 2731 kb)
12094_2019_2066_MOESM4_ESM.docx (17 kb)
Supplementary material 4 Demographic characteristics of GBM patients treated with BCNU/Bev (DOCX 17 kb)
12094_2019_2066_MOESM5_ESM.docx (20 kb)
Supplementary material 5 Detailed description of the levels for the toxicity described in the studies according to Common Toxicity Criteria V 4.0 (DOCX 19 kb)

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Copyright information

© Federación de Sociedades Españolas de Oncología (FESEO) 2019

Authors and Affiliations

  • A. F. Cardona
    • 1
    • 2
    • 3
    Email author
  • L. Rojas
    • 4
    • 5
  • B. Wills
    • 2
    • 6
  • A. Ruiz-Patiño
    • 2
    • 5
  • L. Abril
    • 2
  • F. Hakim
    • 3
    • 7
  • E. Jiménez
    • 3
    • 7
  • N. Useche
    • 3
    • 8
  • S. Bermúdez
    • 3
    • 8
  • J. A. Mejía
    • 3
    • 7
  • J. F. Ramón
    • 3
    • 7
  • H. Carranza
    • 1
    • 2
  • C. Vargas
    • 1
    • 2
  • J. Otero
    • 2
  • P. Archila
    • 2
  • J. Rodríguez
    • 2
  • J. Rodríguez
    • 2
  • J. Behaine
    • 3
  • D. González
    • 3
  • J. Jacobo
    • 3
  • H. Cifuentes
    • 9
  • O. Feo
    • 9
  • P. Penagos
    • 9
    • 10
  • D. Pineda
    • 11
  • L. Ricaurte
    • 2
  • L. E. Pino
    • 12
  • C. Vargas
    • 11
  • J. C. Marquez
    • 11
  • M. I. Mantilla
    • 11
  • L. D. Ortiz
    • 13
  • C. Balaña
    • 14
  • R. Rosell
    • 14
  • Z. L. Zatarain-Barrón
    • 15
  • O. Arrieta
    • 15
  1. 1.Clinical and Translational Oncology Group, Institute of OncologyClínica del CountryBogotáColombia
  2. 2.Foundation for Clinical and Applied Cancer Research (FICMAC)BogotáColombia
  3. 3.Institute of NeuroscienceUniversidad El BosqueBogotáColombia
  4. 4.Clinical Oncology Department, Centro Javeriano de OncologíaHospital Universitario San IgnacioBogotáColombia
  5. 5.Faculty of MedicinePontificia Universidad JaverianaBogotáColombia
  6. 6.Internal Medicine DepartmentJohns Hopkins UniversityBaltimoreUSA
  7. 7.Neurosurgery DepartmentFundación Santa Fe de BogotáBogotáColombia
  8. 8.Division of Neuro-radiology, Radiology DepartmentFundación Santa Fe de BogotáBogotáColombia
  9. 9.Neurosurgery DepartmentClínica del CountryBogotáColombia
  10. 10.Neurosurgery DepartmentNational Cancer Institute (INC)BogotáColombia
  11. 11.Division of Neuro-radiology, Radiology DepartmentClínica del CountryBogotáColombia
  12. 12.Clinical Oncology DepartmentFundación Santa fe de BogotáBogotáColombia
  13. 13.Division of Neuro-Oncology, Clinical Oncology DepartmentClínica de Las AméricasMedellínColombia
  14. 14.Medical Oncology Department, Catalan Institute of OncologyHospital Germans Trias i PujolBadalonaSpain
  15. 15.Instituto Nacional de CancerologíaMéxico CityMexico

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