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Regular use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs) may help some patients with head and neck cancer survive, said a study conducted by Professor Jennifer Grandis of the University of California at San Francisco. The study, which will be published on January 25 in the journal Journal of Experimental Medicine, indicates that NSAIDs are effective in patients with mutations in a gene called PIK3CA, and the researchers suggest that this is due to the fact that NSAIDs lower the levels of an inflammatory molecule called prostaglandin E2. The researchers noted, however, that they are not yet able to make specific recommendations on the type, timing or dosage of NSAIDs that these patients should be taking, and that their results should be corroborated by a prospective clinical trial. .
Squamous cell carcinoma at the head and neck (HNSCC) accounts for about 4% of all cancers in the United States and continues to have a high mortality rate in patients. Smoking, alcohol consumption and human papillomavirus infection are among the risk factors for HNSCC, but several studies have shown that regular use of aspirin can reduce the risk to develop the disease. However, it is not clear whether aspirin or other NSAIDs can promote the survival of patients who have already developed HNSCC. Studies on this issue have so far yielded conflicting results.
One possibility is that NSAIDs are effective only against certain types of HNSCC. About 35% of HNSCC tumors carry mutations that activate the PIK3CA gene, which encodes the catalytic subunit of a key signaling enzyme called PI3Ka. The team of researchers led by Dr. Grandis investigated whether regular use of NSAIDs specifically improved the survival of patients with HNSCC with impaired PIK3CA gene.
The team, which also included researchers from the University of Pittsburgh and Arizona Medical School, badyzed a group of 266 HNSCC patients whose tumors had been surgically removed and which, in most cases, were then treated with adjuvant chemotherapy and / or radiotherapy.
Patients without any alteration of their PIK3CA the gene was no better if they also regularly took NSAIDs (ie two or more doses per week for at least six months). In contrast, regular use of NSAIDs has significantly improved the survival of patients whose PIK3CA the gene has been mutated and / or amplified. Among these patients, NSAIDs increased the five-year overall survival rate from 45% to 78%.
NSAIDs also reduced tumor growth in mice injected with cancer cells harboring a mutant. PIK3CA gene. In badyzing these mice, Grandis and colleagues found that NSAIDs probably inhibited tumor growth by reducing prostaglandin E production.2. This pro-inflammatory molecule has been implicated in various cancers and can be induced by the PI3Ka signaling pathway. NSAIDs can therefore also be effective against a variety of cancers containing activating mutations in PIK3CA gene. Indeed, previous studies have shown that regular use of aspirin can contribute to the survival of colorectal cancer patients with mutations. PIK3CA.
"This study is the first to demonstrate that regular use of NSAIDs confers a significant clinical benefit in patients PIK3CAHNSCC modified, "says Grandis." Inconsistencies in the type, timing and dosages of NSAIDs taken by patients in this study limit our ability to formulate specific therapeutic recommendations. But the magnitude of the apparent benefit, especially given the morbidity and mortality of this disease, deserves further study in a prospective randomized clinical trial. "
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