Tagrisso ?

Hello, first post here, from the husband of a dear wife recently diagnosed with a Grade IV glioblastoma.  Red flags at a UCLA Urgent Care led to a ct scan followed by an MRI and admission.  Complete resection was performed 30 hours later. She followed up with radiochem, and is now in her second course of adjuvant Temodar. We were approved for Optune and are now two weeks in with that, holding firm at about 95% compliance and are also madly ingesting basically everything in the "A" list from the list in the library, thanks to a lot of wonderful help from Mike B here.

Anyway, our doctor suggested we might benefit from a drug called Tagrisso, from AstraZeneca Medicines.  Don't see anything about that in the stacks so far, so was wondering if anyone has any thoughts regarding it. It's proven to be an efficacious treatment for lung cancer but could have crossover value since apparantly it crosses the BBB. 

Chloroquine for GBM with EGFRvIII mutation

EGFRvIII expression triggers a metabolic dependency and therapeutic vulnerability sensitive to autophagy inhibition
http://www.tandfonline.com/doi/pdf/10.1080/15548627.2017.1409926?needAccess=true

Some of the data contained in this study was used as justification for the CHLOROBRAIN trial
https://clinicaltrials.gov/ct2/show/NCT02378532

Plerixafor - new drug to cocktail?

Hello!

1. There is one promising report on the treatment of TMZ+Plerixafor (+Lapatinib  pulse dosing) for glioblastoma:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4965258/
Plerixafor was administered subcutaneously 1 time per week for 2 years.

2. And one ongoing trial studie at phase II:
https://clinicaltrials.gov/ct2/show/study/NCT01977677?term=AMD3100+glioblastoma&rank=1

Plerixafor was administered via continuous intravenous infusion of 400 micrograms/kg/day starting one week prior to end of RT and continuing for 4 weeks.

Here are published abstratcs:
http://ascopubs.org/doi/abs/10.1200/JCO.2017.35.15_suppl.2058
http://ascopubs.org/doi/abs/10.1200/JCO.2016.34.15_suppl.2068

3. There are also several articles about Plerixafor:
https://www.ncbi.nlm.nih.gov/pubmed/27863376
https://www.ncbi.nlm.nih.gov/pubmed/27015814
https://www.ncbi.nlm.nih.gov/pubmed/26023083
https://www.ncbi.nlm.nih.gov/pubmed/25676691
https://www.ncbi.nlm.nih.gov/pubmed/25860928

Stephen wrote that 1 shot of Plerixafor is very expensive, but I am in Delhi (India) and here Plerixafor 24mg/1.2 ml (Celrixafor by Celon Labs) is $ 1000.

What do You think about this medication and what are the tactics of its use more effective?

What do You think about Lapatinib used in the first case, pulse dosing? If it is suitable for all types of glioblastoma? clinical research is also going on:
https://clinicaltrials.gov/show/NCT01591577

Results of the "failed" rindopepimut ACTIV trial published

Rindopepimut with temozolomide for patients with newlydiagnosed, EGFRvIII-expressing glioblastoma (ACT IV):a randomised, double-blind, international phase 3 trial

Primer on CAR T-cell therapy for GBM

This is a useful overview of CAR (chimeric antigen receptor) T-cell therapy and its application to GBM published a few days ago at CancerCommons, written by their chief scientist.

Reengineering Immune System Cells to Fight Glioblastoma (click on link)

Dichloroacetate (DCA) for EGFRvIII positive glioma/glioblastoma

Metabolic targeting of EGFRvIII/PDK1 axis in temozolomide resistant glioblastoma

Click here for study

"Immunocytochemistry experiments conducted on EGFRvIIIR cells revealed intense co-localization of PDK1 and EGFRvIII suggesting that PDK1 function is especially relevant for targeting the EGFRvIIIR-dependent GBMs."

"Mouse GBM xenografts tumor cells exhibited heterogeneous labeling of PDK1/EGFRvIII, with positive areas of staining detected alongside negative ones and the DCA treated tumors showed with very low PDK1/EGFRvIII (Figure 6C). Survival curves plotted revealed that DCA treatment increased the survival rate by more than 5 weeks in EGFRvIII treated mice and 3 weeks in EGFRvIIIR treated mice."

Chloroquine dose for EGFR Amplified/EGFRvIII positive GBM

Hello all, I just also reviewed this 1/17/2017 article regarding GBM and Chloroquine (https://www.sciencedaily.com/releases/2017/01/170117084050.htm) and there seems to be some efficacy with Chloroquine use in BRAF mutation positive GBM.  In our case the BRAF mutation was not detected and I'm wondering if CQ would still have a place in our cocktail in the absence of this mutation.  

However, as was pointed out on this blog, retrospective studies have indicated Chloroquine as being particularly effective in EGFRvIII positive GBM, which is the case with our GBM. I also noted clinical trials going on using CQ in GBM, but could not find any prelim data.  We just finished cycle 2 of TMZ and want to add Chloroquine to our cocktail right away.

Does anyone have an idea regarding the dose (mg) and how it should be taken? (one a day? twice a day? only during the 5/28?  Regards,

Stephen W edited this post to include the following image:

Tumor Genetic Test

All,
We did tumor genetic test at UCSF. Here's the mutations they found...

Please let me know your insights and suggestions for what medicines or therapies are more vs. less effective given these genetic mutations. Mom's radiation is over now and we are planning the next steps. What FDA-approved as well as experimental drug should I push for? thx

Should we take chloroquine

I just looked at the new pdf posted by Ben Williams and it states there that addition of it to the standard treatment did not produce any benefit except for tumors with egfr3. So  I am quite confused now if we should take it or not since our tumor is tp53 mutated , might have pten loss but no egfr3.