Retrospective study of carmustine or lomustine with bevacizumab in recurrent glioblastoma patients who have failed prior bevacizumab.

Abstract

BACKGROUND:

Currently, there are no known effective treatments for recurrent glioblastoma once patients have progressed on a bevacizumab-containing regimen. We examined the efficacy of adding nitrosoureas to bevacizumab in patients who progressed while on an initial bevacizumab-containing regimen.

METHODS:

In this retrospective study, we identified adult patients with histologically confirmed glioblastoma (WHO grade IV) who were treated with lomustine or carmustine in combination with bevacizumab as a second or third regimen after failing an alternative initial bevacizumab-containing regimen. Response rate (RR), 6-month progression free survival (PFS6), and progression-free survival (PFS) were assessed for each treatment.

RESULTS:

Forty-two patients were identified (28 males) with a median age of 49 years (range, 24-78 y). Of 42 patients, 28 received lomustine (n = 22) or carmustine (n = 6) with bevacizumab as their second bevacizumab-containing regimen, and 14 received lomustine (n = 11) or carmustine (n = 3) as their third bevacizumab-containing regimen. While the median PFS for the initial bevacizumab-containing regimen was 16.3 weeks, the median PFS for the nitrosourea-containing bevacizumab regimen was 6.3 weeks. Patients had an RR of 44% and a PFS6 rate of 26% during the initial bevacizumab regimen and an RR of 0% and a PFS6 rate of 3% during the nitrosourea-containing bevacizumab regimen. There was increased grade 3-4 toxicity (45% vs 19%, P = .010) during the nitrosourea-containing bevacizumab regimen relative to the initial bevacizumab regimen. Median overall survival was 18.7 weeks from initiation of the nitrosourea-containing bevacizumab regimen.

CONCLUSION:

The addition of lomustine or carmustine to bevacizumab after a patient has already progressed on a bevacizumab-containing regimen does not appear to provide benefit for most patients and is associated with additional toxicity with the doses used in this cohort.

• Authors: Rifaquat Rahman, Kelly Hempfling, Andrew D Norden, David A Reardon, Lakshmi Nayak, Mikael L Rinne, Rameen Beroukhim, Lisa Doherty, Sandra Ruland, Arun Rai, Jennifer Rifenburg, Debra LaFrankie, Brian M Alexander, Raymond Y Huang, Patrick Y Wen, Eudocia Q Lee
• Journal: Neuro-oncology (Neuro Oncol) Vol. 16 Issue 11 Pg. 1523-9 (Nov 2014) ISSN: 1523-5866 [Electronic] England
• PMID: 24958095 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Antibodies, Monoclonal, Humanized
• Bevacizumab
• Lomustine
• Carmustine

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab
• Brain Neoplasms (drug therapy, mortality, pathology)
• Carmustine (administration & dosage)
• Drug Resistance, Neoplasm (drug effects)
• Female
• Follow-Up Studies
• Glioblastoma (drug therapy, mortality, pathology)
• Humans
• Lomustine (administration & dosage)
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy, mortality, pathology)
• Neoplasm Staging
• Prognosis
• Retrospective Studies
• Salvage Therapy
• Survival Rate
• Young Adult