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 language | English |
|---|---|
| Pages (from-to) | 533-541 |
| Number of pages | 9 |
| Journal | Journal of Neuro-Oncology |
| Volume | 116 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Feb 2014 |
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Keywords
- Bevacizumab
- Fotemustine
- Glioblastoma
- Nitrosoureas
- Recurrence
ASJC Scopus subject areas
- Clinical Neurology
- Cancer Research
- Oncology
- Neurology
Cite this
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 journal › Article
}
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 -