I have a question concerning my girlfriend's father. He is 57 years old. He was diagnosed with a Grade IV, MGMT unmethylated Glioblastoma in the left occipital lobe, September 2018. After the surgery, he received radiotherapy and chemotherapy using VAL-083 in China during 08/11/2018 - 27/06/2019. He had an MRI scan on 20/08/2019 and there is a 17mm*10mm GBM recurrence in the left temporal lobe.
Now his oncologist suggests receiving the standard 5/23 Temozolomide treatment. Since his GBM is MGMT unmethylated, we want to have the cocktail to enhance the performance of Temozolomide for him. He is taking Metformin, Verapamil, Chloroquine and Keppra. We want to choose 1 more medicine from Fluoxetine and Celebrex, which one is better?
Thank you for your help! Best wishes to everyone.
Details of the condition of my father are listed below:
- On 28/09/2018 he had surgery due to a tumor in the left occipital lobe. According to the biopsy, he was diagnosed with a Grade IV Glioblastoma Multiforme, MGMT unmethylated, ki67 70%, IDH1/2(-), 1p/19q non-codeleted, non-diffuse.
- On 08/11/2018, he began to receive radiotherapy and chemotherapy using VAL-083 with a dose of 30mg/m2 IV. But soon he suffered severe myelosuppression and both radiotherapy and chemotherapy are stopped for 2 weeks. After that, the dose of VAL-083 was tuned to 20mg/m2.
- On 24/06/2019, the assessment via MRI is CR I class, complete response (that shows the VAL-083 is effective for him)
- On 27/06/2019, he finished the clinical trial, including 10 cycles of treatment using VAL-083.
- On 20/08/2019, MRI shows that there is a 17mm*10mm enhanced mass in the left temporal lobe (the original tumor was in left occipital lobe).
For sensitizing to TMZ, there is some in vivo evidence showing fluoxetine does suppress MGMT expression in rodents. See figure 6
ReplyDeletehttps://www.dovepress.com/disruption-of-nf-kappab-signaling-by-fluoxetine-attenuates-mgmt-expres-peer-reviewed-fulltext-article-OTT
https://www.dovepress.com/cr_data/article_fulltext/s85000/85948/img/OTT-85948-F06.jpg
Keppra may also help suppress MGMT expression, so higher dosing of that drug before TMZ treatments may help with TMZ sensitization.
https://academic.oup.com/neuro-oncology/article/12/9/917/1187302
"Immunohistochemistry results demonstrated reduced MGMT expression in patient brain tumor samples after treatment with LEV (Fig. 6)."