AI-01 * ARE WE USING TOO MUCH BEVACIZUMAB IN OUR GBM PATIENTS?

Abstract

INTRODUCTION: Compared to traditional chemotherapies, where dose limiting toxicities represent the maximum possible dose, monoclonal antibody therapies are used at doses well below MTD. However, there has been little effort to ascertain whether there is a submaximal dose at which the efficacy/complication ratio is maximized. Thus, despite the general practice of using Bevacizumab (BEV) at dosages of at least 10mg/kg every other week (5mg/week), there has not been any study to our knowledge that this is optimal in terms of minimizing side effects. METHODS: We assessed charts from 59 patients treated at Stanford who received BEV for glioblastoma to survey the incidence of complications relative to the dose of medication/week. All patients were treated with standard upfront chemoradiation. The BEV dose was calculated per week. The toxicity was graded based on the NCI CTCAE, version 4.03. RESULTS: 52 patients received BEV for progression; the others received it as an added upfront treatment to control mass effect during irradiation. The median overall survival was 15 months (2-87). The dose ranged from 1.6 to 10/mg/kg/week with a median of 3.3mg/kg/week. The rate of BEV serious related adverse events was 13.5% (n = 8/59). Compared to a 20% incidence of Grade 3 toxicities in patients receiving > 3.0mg/kg/wk (8/40), no toxicity was seen in patients administered lower doses (0/19), (P 5mg/kg/week. No differences in survival were noted as a function of dose. CONCLUSION: Lower rates of serious BEV related toxicities are noted when lower dosages are used. Furthermore, besides these findings being clinically significant, there is also an added economic benefit to using lower amounts of this very expensive medicine. Further work aimed at optimizing BEV dosage is justified.