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Editorial

Free Access

Second-Line Chemotherapy in Recurrent Glioblastoma - Still Controversial

Franceschi E.

Author affiliations

Department of Medical Oncology, Bellaria-Maggiore Hospital, Azienda USL of Bologna - IRCCS Institute of Neurological Sciences, Bologna, Italy

Corresponding Author

Dr. Enrico Franceschi

Department of Medical Oncology, Bellaria-Maggiore Hospital

Azienda USL of Bologna - IRCCS Institute of Neurological Sciences

Via Altura 3, 40139 Bologna, Italy

enricofra@yahoo.it

Related Articles for ""

Oncol Res Treat 2015;38:345-346

In this issue of Oncology Research and Treatment, Carvalho and Colleagues investigated in a retrospective study the role of second-line treatments in patients with recurrent glioblastoma [1]. As yet, the use of second-line agents remains the most debated topic in this field, and after more than 10 years of studies a clear role for the use of bevacizumab has not been completely established yet. In fact, the first data published in 2005 on response rate and progression-free survival with bevacizumab raised some interest of the scientific community [2]. As a consequence, a first generation of single arm phase II trials were conducted in patients with recurrent glioblastoma [3,4,5], confirming that bevacizumab was able to provide high rates of radiological responses (30-60%) and progression-free survival at 6 months (30-50%). In particular, the BRAIN and the NCI 06-C-0064E trials [4,5] led to accelerated FDA approval of use of bevacizumab in these patients. However, EMA did not approve the treatment due to the lack of direct comparison of bevacizumab with standard chemotherapy in these studies, and also due to the limited reliability of neuroradiological findings using antiangiogenic agents.

A second generation of randomized phase II trials was launched including a nitrosourea-based calibration arm (fotemustine in the AVAREG trial [6], and lomustine in the BELOB trial [7]). In the BELOB trial the combination of bevacizumab and lomustine was also investigated. Despite the fact that these trials were not comparative, the results suggested that bevacizumab was able to obtain similar results in terms of survival rates with respect to chemotherapy, but with a different toxicity profile. Moreover, results were surprisingly superimposable across the AVAREG and BELOB studies, providing an important benchmark for future trials. Data about the combination of bevacizumab and lomustine were also considered worthy of further investigation in a phase III study, and the EORTC re-designed a randomized study with the aim to compare lomustine alone versus a combination of lomustine and bevacizumab. The results of the study of Carvalho et al. [1] are in line with what was obtained in the previous bevacizumab studies, and they suggest that this antiangiogenic agent could be a potential alternative to chemotherapy in recurrent disease.

Despite the increasing scientific knowledge about the use of bevacizumab in glioblastoma treatment some aspects about this agent still remain controversial. For instance, the updated Response Assessment in Neuro-Oncology (RANO) criteria [8] have not yet been prospectively validated, and disease assessment with bevacizumab remains challenging: neuroradiological predictors of outcomes are needed, as well as characterization of molecular profiles that could help clinicians in selection of possible responders amongst patients.

While waiting for studies that could clarify these aspects, clinical factors may help physicians choosing the best treatment: patients' age [6], comorbidities, and previous toxicities to temozolomide may help in the decision for the best therapy.

Disclosure Statement

The Author declares no conflict of interest.


References

  1. Carvalho BF, Fernandes AC, Almeida DS, et al.: Second-line chemotherapy in recurrent glioblastoma: a 2-cohort study. Oncol Res Treat 2015;38: DOI 10.1159/000431236.
  2. Stark-Vance V: Bevacizumab and CPT-11 in the treatment of relapsed malignant glioma, World Federation of Neuro-Oncology Second Quadrennial Meeting. Edinburgh, Scotland, 2005, abstr 342.
  3. Vredenburgh JJ, Desjardins A, Herndon JE, 2nd, et al.: Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007;25:4722-4729.
  4. Kreisl TN, Kim L, Moore K, et al.: Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2008;27:740-745.
  5. Friedman HS, Prados MD, Wen PY, et al.: Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009;27:4733-4740.
  6. Brandes A, Finocchiaro G, Zagonel V, et al.: Randomized phase II trial AVAREG (ML25739) with bevacizumab (BEV) or fotemustine (FTM) in recurrent GBM: final result from the randomized phase II trial. Annals of Oncology 2014;25:iv137.
  7. Taal W, Oosterkamp HM, Walenkamp AM, et al.: Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol 2014;15:943-953.
  8. Wen PY, Macdonald DR, Reardon DA, et al.: Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 2010;28:1963-1972.

Author Contacts

Dr. Enrico Franceschi

Department of Medical Oncology, Bellaria-Maggiore Hospital

Azienda USL of Bologna - IRCCS Institute of Neurological Sciences

Via Altura 3, 40139 Bologna, Italy

enricofra@yahoo.it


Article / Publication Details

Received: May 19, 2015
Accepted: May 21, 2015
Published online: July 01, 2015
Issue release date: August 2015

Number of Print Pages: 2
Number of Figures: 0
Number of Tables: 0

ISSN: 2296-5270 (Print)
eISSN: 2296-5262 (Online)

For additional information: https://www.karger.com/ORT


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References

  1. Carvalho BF, Fernandes AC, Almeida DS, et al.: Second-line chemotherapy in recurrent glioblastoma: a 2-cohort study. Oncol Res Treat 2015;38: DOI 10.1159/000431236.
  2. Stark-Vance V: Bevacizumab and CPT-11 in the treatment of relapsed malignant glioma, World Federation of Neuro-Oncology Second Quadrennial Meeting. Edinburgh, Scotland, 2005, abstr 342.
  3. Vredenburgh JJ, Desjardins A, Herndon JE, 2nd, et al.: Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007;25:4722-4729.
  4. Kreisl TN, Kim L, Moore K, et al.: Phase II trial of single-agent bevacizumab followed by bevacizumab plus irinotecan at tumor progression in recurrent glioblastoma. J Clin Oncol 2008;27:740-745.
  5. Friedman HS, Prados MD, Wen PY, et al.: Bevacizumab alone and in combination with irinotecan in recurrent glioblastoma. J Clin Oncol 2009;27:4733-4740.
  6. Brandes A, Finocchiaro G, Zagonel V, et al.: Randomized phase II trial AVAREG (ML25739) with bevacizumab (BEV) or fotemustine (FTM) in recurrent GBM: final result from the randomized phase II trial. Annals of Oncology 2014;25:iv137.
  7. Taal W, Oosterkamp HM, Walenkamp AM, et al.: Single-agent bevacizumab or lomustine versus a combination of bevacizumab plus lomustine in patients with recurrent glioblastoma (BELOB trial): a randomised controlled phase 2 trial. Lancet Oncol 2014;15:943-953.
  8. Wen PY, Macdonald DR, Reardon DA, et al.: Updated response assessment criteria for high-grade gliomas: response assessment in neuro-oncology working group. J Clin Oncol 2010;28:1963-1972.
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