Bevacizumab and fotemustine for recurrent glioblastoma

A phase II study of AINO (Italian Association of Neuro-Oncology)

Riccardo Soffietti, Elisa Trevisan, Luca Bertero, Paola Cassoni, Isabella Morra, Maria Grazia Fabrini, Francesco Pasqualetti, Ivan Lolli, Anna Castiglione, Giovannino Ciccone, Roberta Rudà

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

The optimal combination of bevacizumab with cytotoxic or cytostatic drugs in recurrent glioblastoma is unknown. We performed a phase 2 trial of combined bevacizumab and fotemustine for patients with glioblastoma at first relapse after radiotherapy and temozolomide. The primary endpoint was 6-month progression-free survival (PFS), while secondary endpoints were overall survival (OS), response rate based on RANO criteria and toxicity. Fifty-four patients with recurrent GBM were enrolled. The authors observed a 6-month PFS rate of 42.6 % (95 % CI 29.3-55.2) and a median PFS of 5.2 months (95 % CI 3.8-6.6). The median OS was 9.1 months (95 % CI 7.3-10.3). Twenty-eight patients (52 %) had a radiographic response, and a significant neurological improvement with steroid reduction was observed in 25/42 symptomatic patients (60 %). MGMT promoter methylation was significantly associated with improved PFS in univariate analysis. Most unifocal tumors at baseline had a focal enhancing progression (76 %), while the diffuse non-enhancing progression accounted for 9.5 %. Response or survival were not associated with any pattern of progression. Survival after failure of treatment was short. Twelve out of 54 patients (22 %) discontinued fotemustine for grade 3/4 myelotoxicity, while 4/54 (7.4 %) discontinued bevacizumab. This study failed to demonstrate a superiority of the combination of bevacizumab and fotemustine over either bevacizumab or fotemustine alone as historical controls. Future studies should explore alternative regimens of combination of the two drugs.

Original languageEnglish
Pages (from-to)533-541
Number of pages9
JournalJournal of Neuro-Oncology
Volume116
Issue number3
DOIs
Publication statusPublished - Feb 2014

Fingerprint

fotemustine
Glioblastoma
Disease-Free Survival
temozolomide
Survival
Survival Rate
Cytostatic Agents
Drug Combinations
Treatment Failure
Methylation
Radiotherapy
Steroids
Bevacizumab
Recurrence

Keywords

  • Bevacizumab
  • Fotemustine
  • Glioblastoma
  • Nitrosoureas
  • Recurrence

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neurology

Cite this

Soffietti, R., Trevisan, E., Bertero, L., Cassoni, P., Morra, I., Fabrini, M. G., ... Rudà, R. (2014). Bevacizumab and fotemustine for recurrent glioblastoma: A phase II study of AINO (Italian Association of Neuro-Oncology). Journal of Neuro-Oncology, 116(3), 533-541. https://doi.org/10.1007/s11060-013-1317-x

Bevacizumab and fotemustine for recurrent glioblastoma : A phase II study of AINO (Italian Association of Neuro-Oncology). / Soffietti, Riccardo; Trevisan, Elisa; Bertero, Luca; Cassoni, Paola; Morra, Isabella; Fabrini, Maria Grazia; Pasqualetti, Francesco; Lolli, Ivan; Castiglione, Anna; Ciccone, Giovannino; Rudà, Roberta.

In: Journal of Neuro-Oncology, Vol. 116, No. 3, 02.2014, p. 533-541.

Research output: Contribution to journalArticle

Soffietti, R, Trevisan, E, Bertero, L, Cassoni, P, Morra, I, Fabrini, MG, Pasqualetti, F, Lolli, I, Castiglione, A, Ciccone, G & Rudà, R 2014, 'Bevacizumab and fotemustine for recurrent glioblastoma: A phase II study of AINO (Italian Association of Neuro-Oncology)', Journal of Neuro-Oncology, vol. 116, no. 3, pp. 533-541. https://doi.org/10.1007/s11060-013-1317-x
Soffietti, Riccardo ; Trevisan, Elisa ; Bertero, Luca ; Cassoni, Paola ; Morra, Isabella ; Fabrini, Maria Grazia ; Pasqualetti, Francesco ; Lolli, Ivan ; Castiglione, Anna ; Ciccone, Giovannino ; Rudà, Roberta. / Bevacizumab and fotemustine for recurrent glioblastoma : A phase II study of AINO (Italian Association of Neuro-Oncology). In: Journal of Neuro-Oncology. 2014 ; Vol. 116, No. 3. pp. 533-541.
@article{051abb8362294c3bb0c00ab0d591b13a,
title = "Bevacizumab and fotemustine for recurrent glioblastoma: A phase II study of AINO (Italian Association of Neuro-Oncology)",
abstract = "The optimal combination of bevacizumab with cytotoxic or cytostatic drugs in recurrent glioblastoma is unknown. We performed a phase 2 trial of combined bevacizumab and fotemustine for patients with glioblastoma at first relapse after radiotherapy and temozolomide. The primary endpoint was 6-month progression-free survival (PFS), while secondary endpoints were overall survival (OS), response rate based on RANO criteria and toxicity. Fifty-four patients with recurrent GBM were enrolled. The authors observed a 6-month PFS rate of 42.6 {\%} (95 {\%} CI 29.3-55.2) and a median PFS of 5.2 months (95 {\%} CI 3.8-6.6). The median OS was 9.1 months (95 {\%} CI 7.3-10.3). Twenty-eight patients (52 {\%}) had a radiographic response, and a significant neurological improvement with steroid reduction was observed in 25/42 symptomatic patients (60 {\%}). MGMT promoter methylation was significantly associated with improved PFS in univariate analysis. Most unifocal tumors at baseline had a focal enhancing progression (76 {\%}), while the diffuse non-enhancing progression accounted for 9.5 {\%}. Response or survival were not associated with any pattern of progression. Survival after failure of treatment was short. Twelve out of 54 patients (22 {\%}) discontinued fotemustine for grade 3/4 myelotoxicity, while 4/54 (7.4 {\%}) discontinued bevacizumab. This study failed to demonstrate a superiority of the combination of bevacizumab and fotemustine over either bevacizumab or fotemustine alone as historical controls. Future studies should explore alternative regimens of combination of the two drugs.",
keywords = "Bevacizumab, Fotemustine, Glioblastoma, Nitrosoureas, Recurrence",
author = "Riccardo Soffietti and Elisa Trevisan and Luca Bertero and Paola Cassoni and Isabella Morra and Fabrini, {Maria Grazia} and Francesco Pasqualetti and Ivan Lolli and Anna Castiglione and Giovannino Ciccone and Roberta Rud{\`a}",
year = "2014",
month = "2",
doi = "10.1007/s11060-013-1317-x",
language = "English",
volume = "116",
pages = "533--541",
journal = "Journal of Neuro-Oncology",
issn = "0167-594X",
publisher = "Springer New York LLC",
number = "3",

}

TY - JOUR

T1 - Bevacizumab and fotemustine for recurrent glioblastoma

T2 - A phase II study of AINO (Italian Association of Neuro-Oncology)

AU - Soffietti, Riccardo

AU - Trevisan, Elisa

AU - Bertero, Luca

AU - Cassoni, Paola

AU - Morra, Isabella

AU - Fabrini, Maria Grazia

AU - Pasqualetti, Francesco

AU - Lolli, Ivan

AU - Castiglione, Anna

AU - Ciccone, Giovannino

AU - Rudà, Roberta

PY - 2014/2

Y1 - 2014/2

N2 - The optimal combination of bevacizumab with cytotoxic or cytostatic drugs in recurrent glioblastoma is unknown. We performed a phase 2 trial of combined bevacizumab and fotemustine for patients with glioblastoma at first relapse after radiotherapy and temozolomide. The primary endpoint was 6-month progression-free survival (PFS), while secondary endpoints were overall survival (OS), response rate based on RANO criteria and toxicity. Fifty-four patients with recurrent GBM were enrolled. The authors observed a 6-month PFS rate of 42.6 % (95 % CI 29.3-55.2) and a median PFS of 5.2 months (95 % CI 3.8-6.6). The median OS was 9.1 months (95 % CI 7.3-10.3). Twenty-eight patients (52 %) had a radiographic response, and a significant neurological improvement with steroid reduction was observed in 25/42 symptomatic patients (60 %). MGMT promoter methylation was significantly associated with improved PFS in univariate analysis. Most unifocal tumors at baseline had a focal enhancing progression (76 %), while the diffuse non-enhancing progression accounted for 9.5 %. Response or survival were not associated with any pattern of progression. Survival after failure of treatment was short. Twelve out of 54 patients (22 %) discontinued fotemustine for grade 3/4 myelotoxicity, while 4/54 (7.4 %) discontinued bevacizumab. This study failed to demonstrate a superiority of the combination of bevacizumab and fotemustine over either bevacizumab or fotemustine alone as historical controls. Future studies should explore alternative regimens of combination of the two drugs.

AB - The optimal combination of bevacizumab with cytotoxic or cytostatic drugs in recurrent glioblastoma is unknown. We performed a phase 2 trial of combined bevacizumab and fotemustine for patients with glioblastoma at first relapse after radiotherapy and temozolomide. The primary endpoint was 6-month progression-free survival (PFS), while secondary endpoints were overall survival (OS), response rate based on RANO criteria and toxicity. Fifty-four patients with recurrent GBM were enrolled. The authors observed a 6-month PFS rate of 42.6 % (95 % CI 29.3-55.2) and a median PFS of 5.2 months (95 % CI 3.8-6.6). The median OS was 9.1 months (95 % CI 7.3-10.3). Twenty-eight patients (52 %) had a radiographic response, and a significant neurological improvement with steroid reduction was observed in 25/42 symptomatic patients (60 %). MGMT promoter methylation was significantly associated with improved PFS in univariate analysis. Most unifocal tumors at baseline had a focal enhancing progression (76 %), while the diffuse non-enhancing progression accounted for 9.5 %. Response or survival were not associated with any pattern of progression. Survival after failure of treatment was short. Twelve out of 54 patients (22 %) discontinued fotemustine for grade 3/4 myelotoxicity, while 4/54 (7.4 %) discontinued bevacizumab. This study failed to demonstrate a superiority of the combination of bevacizumab and fotemustine over either bevacizumab or fotemustine alone as historical controls. Future studies should explore alternative regimens of combination of the two drugs.

KW - Bevacizumab

KW - Fotemustine

KW - Glioblastoma

KW - Nitrosoureas

KW - Recurrence

UR - http://www.scopus.com/inward/record.url?scp=84894031467&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894031467&partnerID=8YFLogxK

U2 - 10.1007/s11060-013-1317-x

DO - 10.1007/s11060-013-1317-x

M3 - Article

VL - 116

SP - 533

EP - 541

JO - Journal of Neuro-Oncology

JF - Journal of Neuro-Oncology

SN - 0167-594X

IS - 3

ER -