Background: Glioblastoma (GB) is the most common malignant primary central nervous system tumor in adults. Standard-of-care therapy includes surgical resection, radiotherapy and temozolomide, but nearly all patients experience disease progression. The purpose of this study was to describe 2 cohorts of patients with recurrent GB submitted to second-line treatment with procarbazine/lomustine/vincristine (PCV) or bevacizumab/irinotecan (BI). Material and Methods: Retrospective analysis of GB patients treated in our center with PCV or BI, after progression with temozolomide, between 2004 and 2012. Results: Among 60 patients, 41 were treated with BI and 19 with PCV. According to the Macdonald criteria, the overall response rate in the BI group was 66% (n = 27) while it was 11% (n = 2) in the PCV group. The median progression-free survival was 5 and 3 months in the BI and PCV group, respectively. The median overall survival (OS) since second-line chemotherapy was 9 months in the BI group and 5 months in the PCV group. The latter group had a worse toxicity profile (grade 3-4: 52.6% vs. 22.0%; grade 1-2: 89.5% vs. 68.3%). Conclusions: The BI cohort had higher response rates, almost twice the OS and a lower degree of toxicity in contrast to the PCV group. The small number of patients and historical cohorts limits these comparisons.

1.
Central Brain Tumor Registry of the United States: Statistical Report: Primary brain tumors in the United States, 2004-2007. Hinsdale, CBTRUS, 2011. www. cbtrus.org.
2.
Easaw JC, Mason WP, Perry J, et al.: Canadian recommendations for the treatment of recurrent or progressive glioblastoma multiforme. Curr Oncol 2011;18: e126-e136.
[PubMed]
3.
Friedman HS, Petros WP, Friedman AH, et al.: Irinotecan therapy in adults with recurrent or progressive malignant glioma. J Clin Oncol 1999;17:1516-1525.
[PubMed]
4.
Fulton D, Urtasun R, Forsyth P: Phase II study of prolonged oral therapy with etoposide (VP16) for patients with recurrent malignant glioma. J Neurooncol 1996;27:149-155.
[PubMed]
5.
Warnick RE, Prados MD, Mack EE, et al.: A phase II study of intravenous carboplatin for the treatment of recurrent gliomas. J Neurooncol 1994;19:69-74.
[PubMed]
6.
Wong ET, Hess KR, Gleason MJ, et al.: Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 1999;17:2572-2578.
[PubMed]
7.
Godard S, Getz G, Delorenzi M, et al.: Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes. Cancer Res 2003;63:6613-6625.
[PubMed]
8.
Lamszus K, Kunkel P, Westphal M: Invasion as limitation to anti-angiogenic glioma therapy. Acta Neurochir Suppl 2003;88:169-177.
[PubMed]
9.
Vredenburgh JJ, Desjardins A, Herndon JE, et al.: Bevacizumab plus irinotecan in recurrent glioblastoma multiforme. J Clin Oncol 2007;25:4722-4729.
[PubMed]
10.
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.
[PubMed]
11.
Hygino da Cruz LC Jr, Rodriguez I, Domingues RC, Gasparetto EL, Sorensen AG: Pseudoprogression and pseudoresponse: imaging challenges in the assessment of posttreatment glioma. AJNR Am J Neuroradiol 2011;32:1978-1985.
[PubMed]
12.
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.
[PubMed]
13.
Iwamoto FM, Abrey LE, Beal K, et al.: Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma. Neurology 2009;73:1200-1206.
[PubMed]
14.
Narayana A, Kunnakkat SD, Medabalmi P, et al.: Change in pattern of relapse after antiangiogenic therapy in high-grade glioma. Int J Radiat Oncol Biol Phys 2012;82:77-82.
[PubMed]
15.
Norden AD, Young GS, Setayesh K, et al.: Bevacizumab for recurrent malignant gliomas: efficacy, toxicity, and patterns of recurrence. Neurology 2008;70:779-787.
[PubMed]
16.
Brada M, Stenning S, Gabe R, et al.: Temozolomide versus procarbazine, lomustine, and vincristine in recurrent high-grade glioma. J Clin Oncol 2010;28:4601-4608.
[PubMed]
17.
Brandes A, Finocchiaro G, Zagonel V, Fabi A, et al.: Randomized phase II trial AVAREG (ML25739) with bevacizumab (BEV) or fotemustine (FTM) in recurrent GBM: final results from the randomized phase II trial. Ann Oncol 2014;25(suppl 4):iv137-iv145.
18.
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 2009;27:740-745.
[PubMed]
19.
Vredenburgh JJ, Desjardins A, Herndon JE, et al.: Phase II trial of bevacizumab and irinotecan in recurrent malignant glioma. Clin Cancer Res 2007;13:1253-1259.
[PubMed]
20.
Wong ET, Gautam S, Malchow C, Lun M, Pan E, Brem S: Bevacizumab for recurrent glioblastoma multiforme: a meta-analysis. J Nat Compr Canc Netw 2011;9:403-407.
[PubMed]
21.
Xu T, Chen J, Lu Y, Wolff JE: Effects of bevacizumab plus irinotecan on response and survival in patients with recurrent malignant glioma: a systematic review and survival-gain analysis. BMC Cancer 2010;10:252.
[PubMed]
22.
Zhang G, Huang S, Wang Z: A meta-analysis of bevacizumab alone and in combination with irinotecan in the treatment of patients with recurrent glioblastoma multiforme. J Clin Neurosci 2012;19:1636-1640.
[PubMed]
23.
Zuniga RM, Torcuator R, Jain R, et al.: Efficacy, safety and patterns of response and recurrence in patients with recurrent high-grade gliomas treated with bevacizumab plus irinotecan. J Neurooncol 2009;91:329-336.
[PubMed]
24.
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.
[PubMed]
25.
Kang TY, Jin T, Elinzano H, Peereboom D: Irinotecan and bevacizumab in progressive primary brain tumors, an evaluation of efficacy and safety. J Neurooncol 2008;89:113-118.
[PubMed]
26.
Paez-Ribes M, Allen E, Hudock J, et al.: Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 2009;15:220-231.
[PubMed]
27.
Gilbert MW, Wang M, Aldape KD, et al.: RTOG 0525: a randomized phase III trial comparing standard adjuvant temozolomide (TMZ) with a dose-dense (dd) schedule in newly diagnosed glioblastoma (GBM). J Clin Oncol 2011;29:abstr 2006.
You do not currently have access to this content.