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Optimizing bevacizumab dosing in glioblastoma: less is more.

Al's Comment:

The "standard" dosage of Avastin for brain tumors was not determined by a trial.  Other cancers used 10mg/kg.  The original small trials for brain tumors used 5mg/kg because of a worry about causing bleeding in the brain - which didn't happen, and it worked well. Then when larger brain tumor trials started up they went with the standard 10mg/kg dose other cancers use.  Some brain tumor doctors still use the 5mg/kg lower dose and feel it works as well or better with less side effects. This study goes a step further and says  less than 3mg may work as well or better with much less side effects. May be worth considering. They had a big increase in survival but there weren't enough patients to say that is significant statistically

 

 


Posted on: 07/06/2017

J Neurooncol. 2017 Jun 30. doi: 10.1007/s11060-017-2553-2. [Epub ahead of print]

Optimizing bevacizumab dosing in glioblastoma: less is more.

Ajlan A1,2, Thomas P3, Albakr A4, Nagpal S3, Recht L3.
 
Author information:
 
1
    Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA. aajlan@stanford.edu.
2
    Department of Neurosurgery, King Saud University, Riyadh, Saudi Arabia. aajlan@stanford.edu.
3
    Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
4
    Department of Neurosurgery, King Saud University, Riyadh, Saudi Arabia.
 
Abstract
 
Compared to traditional chemotherapies, where dose limiting toxicities represent the maximum possible dose, monoclonal antibody therapies are used at doses well below maximum tolerated dose. 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 10 mg/kg every other week for glioma patients, there has not been much prior work examining whether the relatively high complication rates reported with this agent can be decreased by lowering the dose without impairing efficacy. We assessed charts from 80 patients who received BEV for glioblastoma to survey the incidence of complications relative to BEV dose. All patients were treated with standard upfront chemoradiation. The toxicity was graded based on the NCI CTCAE, version 4.03. The rate of BEV serious related adverse events was 12.5% (n = 10/80). There were no serious adverse events (≥grade 3) when the administered dose was (<3 mg/kg/week), compared to a 21% incidence in those who received higher doses (≥3 mg/kg/week) (P < 0.01). Importantly, the three patient deaths attributable to BEV administration occurred in patients receiving higher doses. Patients who received lower doses also had a better survival rate, although this did not reach statistical significance [median OS 39 for low dose group vs. 17.3 for high dose group (P = 0.07)]. Lower rates of serious BEV related toxicities are noted when lower dosages are used without diminishing positive clinical impact. Further work aimed at optimizing BEV dosage is justified.
PMID: 28667595
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