Seattle, WA—A study from a major cancer center adds to evidence that use of nonsteroidal anti-inflammatory drugs (NSAIDs) can be helpful for colorectal cancer patients.

The report published online by the Journal of Clinical Oncology notes that, among long-term colorectal cancer survivors, use of NSAIDS such as aspirin, ibuprofen, and naproxen is associated with about a 25% reduction in all-cause mortality.

Researchers at Fred Hutchinson Cancer Research Center suggest that the drugs are especially effective when taken after diagnosis by colorectal (CRC) patients without tumor mutation in the KRAS gene (KRAS wild-type tumors). NSAID use by this group—which made up about 70% of CRC patients in this study—is associated with a survival benefit of 40%, study authors point out.

“Several other studies have shown an association between NSAIDs and preventing CRC, but this is the first to look so thoroughly at how timing of NSAID use relative to diagnosis and tumor type could make a big difference in survival,” said senior author Polly Newcomb, PhD, MPH, an epidemiologist in the Public Health Division at Fred Hutch. “These results should spark conversations between patients and their doctors. NSAID use is an accepted practice to prevent cardiovascular disease, and their use as a tool against cancer merits similar consideration and study.”

For the observational study, data from 2,419 newly diagnosed patients in the Colon Cancer Family Registry, an international consortium that collects lifestyle, family history and medical information from CRC patients from the U.S, Canada, and Australia, was employed.

Patients were divided into four groups:
• Those who took NSAIDs before, as well as after, diagnosis
• Those who initiated use postdiagnosis
• Those who quit use postdiagnosis
• Those who did not use them at all

Overall, 42% regularly took some form of NSAIDs, both aspirin and nonaspirin.
The study, which also was conducted at the Mayor Clinic in Rochester, Minnesota, as well as the sites in Canada and Australia, followed patients for a median of 10.8 years after diagnosis. Tumormarker testing by genotyping patient samples was used to determine tumor mutations and tumor type, according to the report.

Results indicate that 381 deaths occurred; 100 were a result of CRC. Compared with nonusers, postdiagnostic aspirin-only users had more favorable overall survival (OS), for a hazard ratio of 0.75, and CRC-specific survival, for a hazard ratio of 0.44. That was especially the case among those who initiated aspirin use, with a hazard ratio related to OS of 0.64.

The association between any NSAID use after diagnosis and OS differed significantly by KRAS-mutation status, according to the researchers, who explain that use of any NSAID after diagnosis was associated with improved OS only among participants with KRAS wild-type tumors (HR, 0.60) but not among those with KRAS-mutant tumors (HR, 1.24).

“We now have a better idea of how NSAID use may benefit a subset of patients diagnosed with colorectal cancer,” said first author Xinwei Hua, MPH, ”Next, we need to understand more precisely what the optimal timing, dose and duration of NSAID use should be among patients with KRAS wild-type tumors. We are just beginning to understand the biology underpinning NSAID use on the tumor’s molecular pathways, and it’s very exciting.”

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