Aspirin Use Tied to Lower Risk of Death in Biliary Tract Cancer

Liam Davenport

October 17, 2019

Patients with a rare and life-threatening form of gastrointestinal cancer might live longer if they are aspirin users, with the greatest effect seen in those who had not taken the drug before their cancer diagnosis, the results of a database analysis indicate.

However, the new study only shows correlation and not causation between aspirin use and survival.

Notably, the new findings are in line with previous research in colorectal cancer, said lead author Sarah Jackson, PhD, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland.

Jackson and colleagues looked at the records of almost 3000 patients diagnosed with biliary tract cancer, including cholangiocarcinoma and gall bladder cancer, over a 27-year period.

The research, published online by JAMA Oncology on October 17, showed that aspirin, which was taken by just over 20% of patients, was associated with an improvement in overall survival.

The degree of benefit depended on the individual cancer type but was seen across all tumors, and the effect was greater in those who started taking the drug after they were diagnosed with biliary tract cancer.

While acknowledging that the study is limited by the lack of information on cancer stage and any chemotherapy regimens administered, they say that the "survival benefit of aspirin observed in our study is on par with the current standard of care."

The team suggests that the beneficial effect of aspirin on biliary tract cancer survival may be due to the drug's inhibition of platelet aggregation slowing the spread of metastatic cancer cells.

Jackson nevertheless cautioned that more evidence is required before the findings could be implemented in clinical practice.

"This is one observational study and, while it offers very promising results, we need to replicate these findings in other patient populations and ideally in a randomized clinical trial before we can start making recommendations," she told Medscape Medical News.

The researchers note that biliary tract cancers have an incidence worldwide of less than two per 100,000 people.

Due the lack of symptoms, up to 70% of patients presents with late-stage inoperable or metastatic disease, and they have a poor life expectancy, with 5-year survival rates of 5% to 15% and median survival of less than 1 year.

Previous studies have indicated that aspirin may slow cancer growth via inhibition of cycoloxygenase-2, which promotes cell proliferation and platelet aggregation, and thus reduce cancer mortality.

75 mg Dose of Aspirin for Most

The researchers therefore sought to examine the impact of aspirin use on biliary tract cancer survival by mining the United Kingdom Clinical Practice Research Datalink database of electronic medical records to identify adults diagnosed with the disease between 1990 and 2017.

They included cases of gallbladder cancer, cholangiocarcinoma, ampulla of Vater cancer (AVC), and overlapping lesions of the biliary tract, and excluded patients who had previously been diagnosed with cancer of any kind, aside from nonmelanoma skin cancer.

They identified 2934 biliary tract cancer patients, of whom 1559 (53%) had cholangiocarcinoma, 667 (23%) had gall bladder cancer, 224 (8%) had AVC, and 484 (16%) had overlapping lesions.

Across all cancer types, 256 (9%) of patients were aspirin users at baseline, with an additional 349 (12%) starting on the drug after they were diagnosed with biliary tract cancer. The vast majority were prescribed aspirin at 75 mg.

The team reports that aspirin users were, compared with nonusers, more likely to be older, current statin users, and prediagnosis aspirin users, as well as to more likely to have heart disease and other comorbidities.

In all, 2415 (82%) patients died, at a median survival of 5.8 months (range 2 - 15 months).

Cox proportional hazards regression analysis — taking into account age at diagnosis, sex, comorbidities, statin use at diagnosis, indicators of a healthy lifestyle, and year of diagnosis — revealed that statin use was associated with a reduced risk of death.

Aspirin use was associated with decreased risk of death in patients with gall bladder cancer (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.48 - 0.83), cholangiocarcinoma (HR, 0.71; 95% CI, 0.60 - 0.85), AVC (HR, 0.44; 95% CI, 0.26 - 0.76), and overlapping lesions (HR, 0.68; 95% CI, 0.50 - 0.92).

The team notes that incident aspirin users who had no prior history of using the drug had a larger survival benefit from post-diagnosis aspirin use than those who were prevalent users.

Jackson said that they are "not entirely sure why previous users didn't see as great of a benefit as new users, but we think that it's possible that the tumors that develop in the presence of aspirin may not be as susceptible to the effects of aspirin."

"However, prior users saw a benefit of aspirin, but the association wasn't as large as that of new users," she said.

Jackson added that she did not want to "speculate" on the potential underlying mechanisms, "because we didn't explore the tumor profiles in our study."

The study was funded by National Cancer Institute. The authors have disclosed no relevant financial relationships.

JAMA Oncology. Published online October 17, 2019. Full text

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