Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials

Prof Peter M Rothwell FMedSci a

, Michelle Wilson MSc a, Jacqueline F Price MD b, Prof Jill FF Belch MD c, Prof Tom W Meade FRS d, Ziyah Mehta PhD a

Summary

Background

Daily aspirin reduces the long-term incidence of some adenocarcinomas, but effects on mortality due to some cancers appear after only a few years, suggesting that it might also reduce growth or metastasis. We established the frequency of distant metastasis in patients who developed cancer during trials of daily aspirin versus control.

Methods

Our analysis included all five large randomised trials of daily aspirin (≥75 mg daily) versus control for the prevention of vascular events in the UK. Electronic and paper records were reviewed for all patients with incident cancer. The effect of aspirin on risk of metastases at presentation or on subsequent follow-up (including post-trial follow-up of in-trial cancers) was stratified by tumour histology (adenocarcinoma vs other) and clinical characteristics.

Findings

Of 17 285 trial participants, 987 had a new solid cancer diagnosed during mean in-trial follow-up of 6·5 years (SD 2·0). Allocation to aspirin reduced risk of cancer with distant metastasis (all cancers, hazard ratio 0·64, 95% CI 0·48—0·84, p=0·001; adenocarcinoma, HR 0·54, 95% CI 0·38—0·77, p=0·0007; other solid cancers, HR 0·82, 95% CI 0·53—1·28, p=0·39), due mainly to a reduction in proportion of adenocarcinomas that had metastatic versus local disease (odds ratio 0·52, 95% CI 0·35—0·75, p=0·0006). Aspirin reduced risk of adenocarcinoma with metastasis at initial diagnosis (HR 0·69, 95% CI 0·50—0·95, p=0·02) and risk of metastasis on subsequent follow-up in patients without metastasis initially (HR 0·45, 95% CI 0·28—0·72, p=0·0009), particularly in patients with colorectal cancer (HR 0·26, 95% CI 0·11—0·57, p=0·0008) and in patients who remained on trial treatment up to or after diagnosis (HR 0·31, 95% CI 0·15—0·62, p=0·0009). Allocation to aspirin reduced death due to cancer in patients who developed adenocarcinoma, particularly in those without metastasis at diagnosis (HR 0·50, 95% CI 0·34—0·74, p=0·0006). Consequently, aspirin reduced the overall risk of fatal adenocarcinoma in the trial populations (HR 0·65, 95% CI 0·53—0·82, p=0·0002), but not the risk of other fatal cancers (HR 1·06, 95% CI 0·84—1·32, p=0·64; difference, p=0·003). Effects were independent of age and sex, but absolute benefit was greatest in smokers. A low-dose, slow-release formulation of aspirin designed to inhibit platelets but to have little systemic bioavailability was as effective as higher doses.

Interpretation

That aspirin prevents distant metastasis could account for the early reduction in cancer deaths in trials of daily aspirin versus control. This finding suggests that aspirin might help in treatment of some cancers and provides proof of principle for pharmacological intervention specifically to prevent distant metastasis.

Aspirine zou alvleesklierkanker kunnen voorkomen, maar ook kunnen stimuleren. Twee studies spreken elkaar tegen

Mei 2003:

Het NCI, Nationaal Kanker Instituut van Amerika, maakt deze week melding van een opmerkelijke studie. Opmerkelijk in die zin dat de studie geen gerandomiseerde dubbel gecontroleerde studie is maar een observatiestudie, die normaal gesproken zelden of nooit vermeld wordt door het NCI. FOXnews medlt dit nieuws in het tijdschrift van het NCI, Journal of the National Cancer Institute van gisteren. Het nemen van aspirine - zeg maar elke dag een aspirientje zou maar liefst 43% verschil uitmaken in het risico op het krijgen van alvleesklierkanker bij vrouwen verkerend na de menopauze. De studie is gedaan in de jaren 1992 tot 1999 bij 28283 vrouwen. Of iedereen nu aspirine moet gaan gebruiken lijkt me niet, maar ik wilde dit bericht toch hier plaatsen omdat ik het heel opmerkelijk vind dat zo'n bericht bij zo'n officieel instituut zoveel aandacht krijgt. Opvallend dat een andere studie uit zou wijzen dat aspirine juist kanker zou stimuleren. Zie laatste abstract.

WASHINGTON — Aspirin, already widely used by people hoping to ward off a heart attack, may also be helpful in preventing pancreatic cancer.

In recent years reports of the benefits of aspirin have increased, including modest reductions in the polyps that can lead to colon cancer. Now, University of Minnesota researchers report an apparent association between taking aspirin and reducing rates of often-deadly pancreatic cancer by as much as 43 percent. Their findings are reported in Wednesday's issue of the Journal of the National Cancer Institute.

"This is an intriguing study, more along the lines of hypothesis generating as opposed to testing," said Dr. Ernest Hawk of the National Cancer Institute, who was not part of the research group. "I think that aspirin may very well have this sort of activity but I wouldn't consider it definitive that this point," he said. "They will have to work out the risks and benefits." Hawk noted that this was an observational study, not a randomized, controlled trial. "It provides information that needs to be tested in a controlled study," he said. There have been prior studies of pancreatic cancer that didn't see any statistical effect in aspirin use, Hawk added. Because aspirin can also have side effects, he said that people may not want to run out and start taking it just on the basis of this study, but added that "researchers may want to run out and do (more) studies."

The research team, led by Kristin E. Anderson and Dr. Aaron R. Folsom, studied the use of aspirin and other nonsteroidal anti-inflammatory drugs by 28,283 postmenopausal women who responded to health questionnaires in the Iowa Women's Health Study from 1992 to 1999. Women who took aspirin had a 43 percent lower rate of pancreatic cancer than nonusers and the risk of the cancer declined with increasing frequency of aspirin use, the team reported.

Of 80 cases of pancreatic cancer found in the study, 33 were women who never used aspirin and 27 percent used it less than once a week. There were 10 cases among women who took aspirin two to five times a week and 10 among those using it six times or more weekly.

Risk factors for pancreatic cancer are not known and it is often rapidly fatal with few treatment options.

Aspirine vergroot kansen op alvleesklierkanker

d.d. 2 december 2003: Een epidemiologische studie onder ruim 88.000 vrouwen met geen detecteerbare kanker gedurende 18 jaar heeft uitgewezen dat regelmatig gebruik van aspirine in tegenstelling tot andere berichten dat aspirine kanker zou voorkomen, de kans op alvleesklierkanker vergroot. Het risico is niet dramatisch veel groter maar naarmate de hoeveelheid ingenomen aspirine hoger was bleek ook het risico op het ontwikkelen van alvleesklierkanker groter en is volgens de onderzoekers een bewijs dat aspirine de kans op alvleesklierkanker vergroot. Nature publiceerde abstract van deze studie. Aspirin could increase cancer risk Taking regular aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to help prevent many diseases, including colorectal cancer. Some animal studies and human data have indicated that aspirin might also inhibit pancreatic carcinogenesis, but analysis of cancer incidence as part of a large prospective study into the risk factors for chronic diseases in women shows that aspirin users actually have an increased risk of developing pancreatic cancer. Eva Schernhammer reported these surprising results at a recent American Association of Cancer Research conference — Frontiers in Cancer Prevention Research. A total of 88,378 women with no detectable cancer were included in the Nurses' Health Study and were followed up for 18 years. Aspirin use was assessed at baseline and then updated every 2 years. Participants who were taking two or more aspirin tablets a week had a relative risk (RR) for pancreatic cancer of 1.20 compared with non-users. Increasing the duration of aspirin use was also associated with a significantly increased risk: women who had taken aspirin regularly for 20 years or more had a RR of 1.58. Women who had taken 14 or more aspirin tablets per week for 4 or more years had a RR of 1.86. The authors conclude that extended regular use of aspirin is associated with increased risk of pancreatic cancer in women. Other risk factors include smoking and obesity, but taking these factors into account did not alter the association of pancreatic cancer risk with aspirin use. There is some evidence that regular aspirin use might cause pancreatitis — inflammation of the pancreas that has been linked to an increased risk of developing pancreatic cancer — so this connection is worth investigating further. FURTHER READING Schernhammer, E. et al. A prospective study of aspirin use and risk of pancreatic cancer in women. AACR Proc. Front. Cancer Prev. Res. A162 (2003)

aspirine, alvleesklierkanker, metastases, adenocarcinomen