Cyclooxygenase-Dependent Tumor Growth through Evasion of Immunity
(This study is also open access and can be dowloaded as a free PDF from the link above)
In this study, immunocompetent mice bearing melanoma syngrafts were treated with either aspirin (in the drinking water), or an anti-PD-1 antibody (similar to nivolumab or pembrolizumab), or both drugs combined. Aspirin alone had no significant effect on tumor growth, the PD-1 antibody had a modestly significant effect, while the combination of both agents was highly effective, with over 50% of mice rejecting the tumors. When a larger number of melanoma cells was injected into a new set of mice, neither drug alone had any effect on tumor growth, while the combination of both aspirin and PD-1 antibody led to tumor regression at day 30.
Similar experiments were repeated with celecoxib/Celebrex (injected intraperitoneally), with similar results, though slightly less effective than aspirin in the melanoma model.
A similar experiment was then carried out using aspirin and the PD-1 antibody, but this time using colorectal cancer cells. Again, aspirin alone was ineffective, the PD-1 antibody was modestly effective, while the combination was highly effective, with about 30% of the animals rejecting the tumors.
Note that a dosage reduction of Depakote may be required if taken concurrently with aspirin:
ReplyDelete"A study involving the co-administration of aspirin at antipyretic doses (11 to 16 mg/kg) with valproate to pediatric patients (n=6) revealed a decrease in protein binding and an inhibition of metabolism of valproate. Valproate free fraction was increased 4-fold in the presence of aspirin compared to valproate alone. The β-oxidation pathway consisting of 2-E-valproic acid, 3-OH-valproic acid, and 3-keto valproic acid was decreased from 25% of total metabolites excreted on
valproate alone to 8.3% in the presence of aspirin. Caution should be observed if valproate and aspirin are to be co-administered."
From Depakote prescribing information
Hi Stephen, did any of the studies try Celebrex with Pd-1 in gbm patients? Is it safe to take either aspirin or Celebrex with avastin? Thanks
ReplyDeleteNo I've never heard of PD-1 antibodies combined with Celebrex for GBM. The study mentioned in the post above were in mice only, and none of the models were GBM models.
DeleteI've not heard of problems combining celecoxib with Avastin, although there is a theoretical risk given that both can increase clotting. I've seen warnings about combining Avastin and aspirin, but low-dose aspirin may be okay:
http://www.ncbi.nlm.nih.gov/pubmed/17686822
Avastin apparently increases risk of thromboembolism (clotting) as well as hemorrhage and bleeding, which is a little confusing.
http://www.webmd.com/cancer/news/20081118/cancer-drug-avastin-raises-blood-clot-risk
http://www.ncbi.nlm.nih.gov/pubmed/21051914
Thanks so much Stephen. My husband is on avastin now and we just started Celebrex a week ago for the exact reason of fearing giving aspirin along with avastin. Would it be worth it to try a baby aspirin every other day? I am failing to understand how avastin can cause clotting and bleeding at the same time. Thanks so much
ReplyDeleteI would have to research this in more detail before I could advise further. I can't say I understand the mechanism behind Avastin increasing risk of both blood clots as well as hemorrage.
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