I spotted this paper and thought it was best to share: “Do statins, ACE inhibitors or sartans improve outcome in primary glioblastoma?” Although I’ve not read the full paper, it’s worth noting that they concluded:
This secondary analysis of two large glioblastoma trials thus was unable to detect evidence for an association of the use of statins, ACEI or sartans with outcome in patients with newly diagnosed glioblastomaShould we abandon ACE inhibitors, etc?
Not necessarily.
ReplyDeleteFor one, several papers have shown this class of drugs (ACEi and sartans) to be helpful in reducing the daily steroid requirement for those trying to wean of dexamethasone etc. The losartan trial didn't show a positive outcome, but this might not have been the ideal sartan. The CUSP-ND discussion group (of which I was a part) chose telmisartan as having better potential for getting into the brain. So this activity is apart from any survival benefit.
Likewise, the ACE inhibitors used by the majority of patients in the study you mention, might not have been the optimal ones in terms of getting into the brain.
The study that was most convincing for me for adding ACE inhibitors to an anti-tumor cocktail was this one:
https://www.ncbi.nlm.nih.gov/pubmed/23333075
Angiotensin II drives the production of tumor-promoting macrophages.
As we know tumor-promoting macrophages can make up a significant share of the bulk of a glioblastoma (up to 30% in some studies).
In addition, when clinical trials that show a negative result overall (no significant prolongation of survival on average), this doesn't mean that no patient benefitted. There might be a small subgroup that benefits. So one hypothesis could be that tumors with the largest tumor-promoting macrophage component might be more responsive to ACE inhibition.
Just a theory, but I feel these broad observational studies not finding a survival association can lead to a too easy dismissal of a potentially helpful drug, if proper attention is paid to adequate dosing, choosing the right drug in the class with the best pharmacokinetic/pharmacodynamic properties etc.