Metronomic chemotherapy with daily, oral etoposide plus bevacizumab for recurrent malignant glioma: a phase II study

• DOI: 10.1038/sj.bjc.6605412
• Publication Date: 2009-11-18T02:07:39Z
• Authors: D A Reardon; A Desjardins; J J Vredenburgh; S Gururangan; J H Sampson; S Sathornsumetee; R E McLendon; J E Herndon; J E Marcello; J Norfleet; A H Friedman; D D Bigner; H S Friedman
• Keywords: Progression-free survival; Clinical endpoint; Lomustine

We evaluated bevacizumab with metronomic etoposide among recurrent malignant glioma patients in a phase 2, open-label trial. A total of59 patients, including 27 glioblastoma (GBM) and 32 grade 3 glioma, received 10 mg kg−1 biweekly 50 m−2 daily for 21 consecutive days each month. The primary end point was 6-month progression-free survival, secondary points included safety overall survival. Vascular endothelial growth factor (VEGF), VEGFR-2, carbonic anhydrase 9 (CA9) hypoxia-inducible factor-2α (HIF-2α) were assessed semiquantitatively archival tumours using immunohistochemistry correlated outcome. Among GBM the survivals 40.6% 44.4%, radiographic response rates 22% 37% median 63.1 44.4 weeks, respectively. Hypertension predicted better outcome both whereas high CA9 low VEGF associated poorer survival (PFS) those GBM. most common ⩾3 adverse events neutropaenia (24%), thrombosis (12%), infection (8%) hypertension (3%). Two had asymptomatic, 1 intracranial haemorrhage one on-study death occurred because of pulmonary embolism. Bevacizumab has increased toxicity compared previous reports monotherapy. Its anti-tumour activity is similar to that monotherapy or plus irinotecan. (ClinicalTrials.gov: NCT00612430).