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Survival Benefits for Low-Dose Aspirin in GI Cancers

Susman, Ed

doi: 10.1097/01.COT.0000473585.57651.8b




VIENNA, Austria—Some cancer treatments can cost thousands of dollars a dose, but one baby aspirin a day, which costs only a few pennies, appears to prolong survival among patients diagnosed with gastrointestinal malignancies, researchers reported here at the European Cancer Conference (Abstract 2306).

Remarkably, about 75 percent of patients who began a daily aspirin regimen after being diagnosed with gastrointestinal cancers achieved five-year survival compared with 42 percent of patients not on aspirin therapy, said Martine Frouws, MD, a PhD student at Leiden University Medical Centre in the Netherlands.

And when the researchers broke down the outcomes by organ site, use of aspirin significantly extended survival in esophageal, stomach, colon, and rectal cancers, and well as showing a trend in hepatobiliary cancer, Frouws noted at an ECC news conference. No such increase, however, was seen for pancreatic cancer.

“Aspirin is a very cheap drug and doctors have wide experience in using it,” she said. “It is generally well-tolerated with relatively few side effects but when administered to patients with gastrointestinal cancers the patients do have to be monitored closely.

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Study Details

The researchers collected data on survival for all patients who had gastrointestinal tumors between 1998 and 2011 from the population-based Eindhoven Cancer Registry in the Netherlands and linked that with drug dispensing data from the PHARMO Database Network. Outcomes were reviewed for 17,315 patients, of whom 8.3 percent used aspirin only after a diagnosis of cancer.

The approximately 30 percent of patients taking aspirin at the time of diagnosis were excluded from the trial, and the researchers focused on the 9,528 patients who did not use aspirin before diagnosis. That left 8,365 patients who were not aspirin users and 1,143 who began their aspirin regimens when they were diagnosed with a GI malignancy.

Frouws said that the largest group of patients in the study were those who had been diagnosed with colorectal cancer (4,081 patients, about 43% of the total cohort). The next largest group were patients diagnosed with rectal cancer (2,370 patients, about 25%). Another 972 patients (10%) had been diagnosed with esophageal cancer. The study also included patients with stomach, pancreatic, hepatobiliary, small intestine, and anal cancers.

Median follow-up time for all patients was 26.5 months, and the median five-year overall survival rate was 56 percent.

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Ongoing Related Studies

“In this trial there was no information available on the side effects of aspirin therapy in these patients,” Frouws said at the news conference. “For that reason, randomized, controlled clinical trials have to be done to confirm this effect in cancer.”

She is now coordinating The Aspirin Study in the Netherlands, one of several similar trials underway around the world, including a cooperative study in the United States and Australia. The Netherlands trialists began recruiting patients for their five-year trial in January of this year.

She noted that aspirin has been looked at retrospectively in mainly colorectal cancer, but the researchers wanted to see what the results might be in all forms of gastrointestinal malignancies.

The moderator of the news conference, Peter Naredi, MD, Professor and Chairman of Surgery at Sahlgrenska Academy of the University of Gothenburg in Sweden, asked the audience of approximately 50 international reporters how many used aspirin therapy. Only a handful of the journalists raised their hands. Naredi said that in the general population, about 50 percent of patients take aspirin.

“We really don't prescribe aspirin to all our patients,” he said in an interview. “I find it amazing how a 100-year-old medicine can be good for these patients.” He said he would like to see older populations—patients in their 50s and 60s—use aspirin because of its positive effects on heart disease as well as cancer.

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Variety of Stages

Frouws noted that the patients in the study had all stages of cancer at diagnosis—“When you look at the effects of aspirin stratified by cancer stage, you still see the same positive effects.”

The beneficial effect of aspirin use on survival was seen in patients with GI tumors after adjusting for potential confounding factors such as sex, age, stage of cancer, surgery, radiotherapy, chemotherapy, and other medical conditions or disorders, she said.

“In most observational studies an ‘intention to treat’ method is used for analysing aspirin's effect,” Frouws explained. “In this study we analyzed each separate prescription per patient, and were therefore able to achieve a more exact estimate of the effect of aspirin on cancer survival.

“Now we would like to analyze tumor material from these patients to try and discover which patients would benefit from aspirin treatment. Through studying the characteristics of tumors in patients where aspirin was beneficial, we should be able to identify patients who could profit from such treatment in the future,” she said.

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Mechanism of Action: Anti-platelet Effect?

Researchers in the past have suggested that the beneficial effect of aspirin in cancer is due to its anti-platelet effect. Circulating tumour cells are thought to “hide” themselves from the immune system with the help of the clothing of platelets that surround them. Aspirin inhibits platelet function and therefore allows the immune system to recognize circulating tumor cells and eliminate them.

“Medical research is focusing more and more on personalized medicine, but many personalized treatments are expensive and useful only in small populations,” Frouws said. “We believe that our research shows quite the opposite, demonstrating the considerable benefit of a cheap, well-established, and easily obtainable drug in a larger group of patients, while still targeting the treatment to a specific individual.”

Naredi said: “We have good evidence that the frequent use of aspirin in the population can prevent some cases of colorectal cancer. Now, Dr. Frouws and colleagues show that aspirin also improved survival compared with those who did not use it. With more and more data to support the beneficial role of aspirin, we must consider whether we should recommend it to a wider public.”

Also asked for his perspective, Nadir Arber, MD, Head of the Integrated Cancer Prevention Center at Tel Aviv Sourasky Medical Center in Israel, said: “Aspirin may serve as the magic bullet because it can target and prevent ischemic heart disease, cancer, and Alzheimer's disease—the three major health catastrophes in the third millennium.

“Dr. Frouws and her colleagues tell us that not only can aspirin prevent disease, but low-dose aspirin is important as an adjunct therapy for gastrointestinal cancers. The appropriate dosage and duration of aspirin use and risk/benefit ratios of aspirin use remain to be determined but, in the area of precision medicine, genetic information and blood and/or urinary biomarkers may help in tailoring treatment to those who will benefit most, while limiting adverse effects.”

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All the abstracts from the meeting are available at:

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