PT  - JOURNAL ARTICLE
AU  - Norden, A. D.
AU  - Young, G. S.
AU  - Setayesh, K.
AU  - Muzikansky, A.
AU  - Klufas, R.
AU  - Ross, G. L.
AU  - Ciampa, A. S.
AU  - Ebbeling, L. G.
AU  - Levy, B.
AU  - Drappatz, J.
AU  - Kesari, S.
AU  - Wen, P. Y.
TI  - Bevacizumab for recurrent malignant gliomas
AID  - 10.1212/01.wnl.0000304121.57857.38
DP  - 2008 Mar 04
TA  - Neurology
PG  - 779--787
VI  - 70
IP  - 10
4099  - http://n.neurology.org/content/70/10/779.short
4100  - http://n.neurology.org/content/70/10/779.full
SO  - Neurology2008 Mar 04; 70
AB  - Background: Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor, may have activity in recurrent malignant gliomas. At recurrence some patients appear to develop nonenhancing infiltrating disease rather than enhancing tumor. Methods: We retrospectively reviewed 55 consecutive patients with recurrent malignant gliomas who received bevacizumab and chemotherapy to determine efficacy, toxicity, and patterns of recurrence. Using a blinded, standardized imaging review and quantitative volumetric analysis, the recurrence patterns of patients treated with bevacizumab were compared to recurrence patterns of 19 patients treated with chemotherapy alone. Results: A total of 2.3% of patients had a complete response, 31.8% partial response, 29.5% minimal response, and 29.5% had stable disease. Median time to radiographic progression was 19.3 weeks. Six-month progression-free survival (PFS) was 42% for patients with glioblastoma and 32% for patients with anaplastic glioma. In 23 patients who progressed on their initial therapy, bevacizumab was continued and the concurrent chemotherapy agent changed. In no case did the change produce a radiographic response, but two patients had prolonged PFS of 20 and 31 weeks. Recurrence pattern analysis identified a significant increase in the volume of infiltrative tumor relative to enhancing tumor in bevacizumab responders. Conclusions: Combination therapy with bevacizumab and chemotherapy is well-tolerated and active against recurrent malignant gliomas. At recurrence, continuing bevacizumab and changing the chemotherapy agent provided long-term disease control only in a small subset of patients. Bevacizumab may alter the recurrence pattern of malignant gliomas by suppressing enhancing tumor recurrence more effectively than it suppresses nonenhancing, infiltrative tumor growth. AA=anaplastic astrocytoma; AG=anaplastic glioma; CR=complete response; GBM=glioblastoma; EIAED=enzyme-inducing antiepileptic drug; FLAIR=fluid-attenuated inversion recovery; KPS=Karnofsky Performance Status; MR=minimal response; PFS=progression-free survival; PR=partial response; rFPR=relative FLAIR progression ratio; rNTR=relative nonenhancing tumor ratio; T1W=T1-weighted; VEGF=vascular endothelial growth factor.