Wednesday, December 4, 2019

NSAID's and cancer (Colon and melanoma specifically!) ~


Much has been written in the literature regarding NSAID use and melanoma. NSAID's are drugs like aspirin, ibuprofen, naproxen, and lots of prescription ones, that block COX enzymes.  Enzymes that produce prostaglandins which lead to inflammation, pain and fever when left to do their own thing.  By blocking the enzyme, NSAID's reduce the prostaglandins and the unpleasantness they cause.  I first reported on them in 2012!  Here is a break down of how they might work in melanoma world from 2015:  An aspirin a day...keeps melanoma at bay....and makes immunotherapy work better!!!! 
Here are a zillion additional reports:  NSAID's - do they help or not? 
Basically, the data (and reports) cover:
"YES!!!  NSAID's make immunotherapy work better!"   "NSAID's increase survival in melanoma patients."  "No, NSAID's make no difference."

Though these drugs are not to be trifled with despite being accessible over the counter, most data says at worst they "do no harm".  Given the aches and pains immunotherapy causes, I've long said you would be hard pressed to find a patient on immunotherapy who did NOT partake in the use of NSAID's!!  I know I certainly took my share of advil during my treatment!!!  Now, there's this:

The Impact of Nonsteroidal Anti-Inflammatory Drugs, Beta Blockers, and Metformin on the Efficacy of Anti-PD-1 Therapy in Advanced Melanoma.  Wang, McQuade, Rai, et al.  Oncologist.  2019 Nov 29.

Anti-programmed cell death protein-1 (anti-PD-1) therapy has greatly improved outcomes of patients with melanoma; however, many fail to respond. Although preclinical studies suggest a potentially synergistic relationship with anti-PD-1 therapy and certain concurrent medications, their clinical role remains unclear. Here, we retrospectively evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and other drugs in 330 patients with melanoma treated with anti-PD-1 therapy from four academic centers. In the cohort, 37% of patients used NSAIDs including aspirin (acetylsalicylic acid; ASA; 47%), cyclooxygenase (COX)-2 inhibitors (2%), and non-ASA/nonselective COX inhibitor NSAIDs (59%). The objective response rates (ORRs) were similar in patients with NSAID (43.4%) and no NSAID (41.3%) use with no significant difference in overall suvival (OS). There was a trend toward improved progression-free survival (PFS) in patients who took NSAIDs (median PFS: 8.5 vs. 5.2 months). Most patients (71.3%) took NSAIDs once daily or as needed. Multivariate analysis did not reveal an association with NSAID use with ORR, PFS, or OS. Concurrent use of metformin or beta blockers did not affect ORR, PFS, or OS. Our study found no conclusive association of concurrent NSAID or other medication use with improved outcomes in patients with melanoma treated with anti-PD-1 therapy. Larger and more systematic analysis is required to confirm these findings.

Given my current condition, it is pertinent that my 2015 report started with this quote:
 "NSAID's, including aspirin, decrease the incidence and mortality from colon cancer in humans by 45% to 50%."  DuBois, Cancer Research, 56(4), 1996.

Now, there's this - The Association between NSAID use and Colorectal Cancer Mortality: Results from the Women's Health Initiative

Which notes:  "Randomized trial evidence demonstrates that non-steroidal anti-inflammatory drug (NSAID) use, particularly long-term use, reduces the incidence of colorectal neoplasia. Recent data also suggests an inverse association between NSAID use and death due to colorectal cancer (CRC). We examined the association between NSAID use and CRC mortality among 160,143 post-menopausal women enrolled in the Women's Health Initiative. Women provided details on medication use at baseline and three years after enrollment. Overall, NSAID use at baseline was not associated with CRC mortality. However, women who reported NSAID use at both baseline and year-three experienced reductions in CRC mortality compared to non-users.  Results suggest that NSAID use is associated with lower CRC mortality among post-menopausal women who use these medications more consistently over time. Our results support prolonged NSAID use in post-menopausal women for the prevention of poor CRC outcomes."

I have discussed all of this with my various docs.  They didn't have too much to say or contribute on the subject one way or another.  However, I was given their blessing to start an aspirin regimen of one baby aspirin (81mg) per day.  So, I did!  For what it's worth! - c

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