Disconnect Between Recurrence-Free Survival and Overall Survival for Newly Diagnosed Glioblastoma Patients Receiving Adjuvant Bevacizumab

Abstract

gliomas. This phase II study evaluates the efficacy and safety of using bevacizumab with the addition of lithium, which has been shown to have anti-invasive activity in glioma cells by inhibiting glycogen synthase kinase-3 (GSK-3), in newly diagnosed high grade gliomas. Materials/Methods: From 2010 through 2012, 28 HGG patients (WHO grade III 8, IV 20) with residual disease after surgery were treated with involved-field radiation therapy to 5940 cGy and concomitant temozolomide (TMZ) (75 mg/m daily for 42 days) along with BEV (10 mg/kg every 2 weeks), starting 29 days after surgery. This was followed by six 28day cycles of TMZ (150 mg/m on days 1-7, BEV (10 mg/kg) on days 8 and 22, and lithium 300 mg BID. Lithium was increased every 7 days up to 600 mg BID with a serum lithium goal level of 0.8 to 1.2 mEq/L. Results: The median follow-up was 10.5 months (range, 1.9-29.0 months). Twenty-two patients (78.6%) received at least one dose of lithium and six patients completed the entire course of therapy. The median number of BEV infusion was 9 (range, 2-33). Six patients discontinued trial due to skin sensitivity (n Z 3), pulmonary embolism (n Z 1), infection (n Z 1), and hematological toxicity (n Z 1). Four patients experienced dose limiting lithium toxicity which included drowsiness (n Z 3) and tremor (n Z 1). No patients experienced grade 3/4 intra-cranial hemorrhage. The median progression free survival (PFS) and overall survival (OS) were 9.3 and 24.5 months respectively. For grade IV gliomas, the 12-month PFS and OS were 31.9% and 59.3% respectively. For the 22 patients who received lithium, the 12-month PFS and OS were 42.5% and 75.6% respectively. Conclusions: These preliminary results show that targeting both angiogenesis and invasion of high grade glioma along with conventional therapy is both feasible and effective. Author Disclosure: M. Tam: None. M. Gruber: None. D. Gruber: None. J. Golfinos: None. E. Parker: None. D. Zagzag: None. A. Narayana: None.