There are many articles on the possible benefits zoledronic acid in the treatment of glioblastoma.
https://www.ncbi.nlm.nih.gov/pubmed/?term=Zoledronic+glioblastoma
For example, MTZ Regimen (2016) suggests using:
oral minocycline 100 mg three times daily, oral telmisartan 80 mg twice daily, and intravenous zoledronic acid 4 mg once every 28 days
https://www.dovepress.com/toward-a-noncytotoxic-glioblastoma-therapy-blocking-mcp-1-with-the-mtz-peer-reviewed-fulltext-article-OTT
https://www.ncbi.nlm.nih.gov/pubmed/27175087
Since many patients with glioblastoma include in their cocktails minocycline and telmisartan (or captopril), may be necessary to think about adding an injection of zoledronic acid as non-toxic supplement, 4mg once every 28 days?
https://www.ncbi.nlm.nih.gov/pubmed/?term=Zoledronic+glioblastoma
For example, MTZ Regimen (2016) suggests using:
oral minocycline 100 mg three times daily, oral telmisartan 80 mg twice daily, and intravenous zoledronic acid 4 mg once every 28 days
https://www.dovepress.com/toward-a-noncytotoxic-glioblastoma-therapy-blocking-mcp-1-with-the-mtz-peer-reviewed-fulltext-article-OTT
https://www.ncbi.nlm.nih.gov/pubmed/27175087
Since many patients with glioblastoma include in their cocktails minocycline and telmisartan (or captopril), may be necessary to think about adding an injection of zoledronic acid as non-toxic supplement, 4mg once every 28 days?
As usual, the main barrier in the usefulness of zoledronic acid for GBM is likely a pharmacokinetic one.
ReplyDelete"The lack of clear evidence of ZOL-induced anti-cancer effects is likely due to its unfavourable pharmacokinetic profile. In fact, it accumulates almost exclusively in the bone and has a short serum half-life (only 15 min) not reaching active anti-tumor concentrations [15]. Our group demonstrated that the use of nanotechnology-based formulations overcomes these limitations due to bad ZOL pharmaco-distribution changing this drug in a powerful anticancer agent"
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4279385/
And similarly:
"Unfortunately, ZOL has a very short plasma half-life and
tends to accumulate in the bone, which results in far below
therapeutically effective concentrations that reach tumor
tissues"
https://pdfs.semanticscholar.org/ada1/00d6b42fe3de887ecf3d711d2717a9e21990.pdf
The MTZ document provides an interesting hypothesis that zoledronic acid would affect the tumor-infiltrating macrophage population more than the tumor cells, so could work via this indirect effect. Unfortunately there was no in vivo support of this hypothesis available (only in vitro, ex vivo). The 2016 document states "We are planning a pilot clinical trial of the MTZ Regimen
in primary glioblastoma", which is also interesting but I haven't seen any other references to this trial.