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A phase 2 trial of single‐agent bevacizumab given in an every‐3‐week schedule for patients with recurrent high‐grade gliomas
Author(s) -
Raizer Jeffrey J.,
Grimm Sean,
Chamberlain Marc C.,
Nicholas M. Kelly,
Chandler James P.,
Muro Kenji,
Dubner Steven,
Rademaker Alfred W.,
Renfrow Jaclyn,
Bredel Markus
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25462
Subject(s) - medicine , bevacizumab , glioma , vascular endothelial growth factor , surgery , gastroenterology , anaplastic astrocytoma , phases of clinical research , progression free survival , chemotherapy , astrocytoma , vegf receptors , cancer research
BACKGROUND: The authors evaluated a 3‐week schedule of bevacizumab in patients with recurrent high‐grade glioma (HGG). METHODS: Patients received bevacizumab 15 mg/kg every 3 weeks and were evaluated every 6 weeks until tumor progression. Tissue correlates were used to quantify tumor content of vascular endothelial growth factor A (VEGFA) and vascular endothelial growth factor receptor‐2 (VEGFR2). RESULTS: Of 61 patients who were treated (35 men and 26 women; median age, 52 years; age range, 21‐78 years), 50 patients had glioblastoma multiforme (GBM), and 11 patients had anaplastic glioma (AG). The median number of previous chemotherapies was 2 (range, 1‐5 previous chemotherapies), and 16 patients had received ≥3 previous chemotherapies. The median number of bevacizumab doses was 4 (range, 1‐20 doses), and 45% of patients received >5 doses. The toxicities observed were primarily grade 1 and 2, and the most common were fatigue, hypertension, and headache. One grade 2 intratumoral bleed and 1 bowel perforation were reported. For patients with GBM, the 6‐month progression‐free survival rate was 25%, the median time to tumor progression was 10.8 weeks, and the median overall survival was 25.6 weeks. The best response included a partial response in 15 patients (24.5%) and stable disease in 31 patients (50.8%) patients; radiographic recurrence patterns included increased changes in fluid attenuation inversion recovery (24%) and multifocal recurrence (20%). The median survival after bevacizumab failure was 10 weeks. The ratio of tumor VEGFA/VEGFR2 was increased in patients aged >55 years; an increased VEGFA/VEGFR2 ratio was correlated nonsignificantly with decreased survival ( P = .052). CONCLUSIONS: An every‐3‐week schedule of bevacizumab had antitumor activity and was relatively nontoxic for patients with recurrent HGG. The predictive value of VEGFA/VEGFR2 in tumor will require validation in a larger patient cohort. Cancer 2010. © 2010 American Cancer Society.