(ChemotherapyAdvisor) – The case for daily use of aspirin to prevent as well as possibly treat cancer and reduce risk of distant metastases was bolstered by three meta-analyses in The Lancet and Lancet Oncology published online March 21.
The three studies, all conducted by Rothwell et al. from the University of Oxford and John Radcliffe Hospital, Oxford, UK, focus on the short-term effects of daily aspirin on cancer incidence, mortality and nonvascular death; the effect of daily aspirin on risk of metastasis; and the effects of regular aspirin on long-term cancer incidence and metastasis. Previously, the investigators had established that daily aspirin reduced long-term risk of death due to cancer.
Study 1: Individual patient data from 51 randomized trials of daily aspirin vs. no aspirin to prevent vascular events. Risk of cancer death was reduced by 15% vs. controls, improving to a 37% reduced risk of a cancer death for those on aspirin beginning at five years. Nonvascular deaths were reduced overall by 12% and accounted for 91% of the deaths prevented. Use of low-dose aspirin reduced incidence of cancer in men (23%) and women (25%) from three years onward. Case fatality from major extracranial bleeds was lower on aspirin than on control (8/203 vs. 15/132; OR=0.32; P=0.009).
“In view of the very low rates of vascular events in recent and ongoing trials of aspirin in primary prevention, prevention of cancer could become the main justification for aspirin use in this setting,” they wrote.
Study 2. Prospective study of metastases of cancers diagnosed during five large randomized cardiovascular prevention trials of daily aspirin 75mg or higher vs. control. Patients allocated to aspirin had a reduced risk of cancer with distant metastasis by 36%, risk of adenocarcinoma by 46%, and of other solid cancers by 18%. Aspirin reduced risk of adenocarcinoma with metastasis at initial diagnosis by 31% and risk of metastasis on subsequent follow-up in patients without metastasis initially by 55%; this reduction was 74% in patients with colorectal cancer and 69% in those who remained on trial treatment up to or after diagnosis. Mean follow-up was 6.5 years.
“These findings provide the first proof in man that aspirin prevents distant cancer metastasis,” Rothwell et al. noted. “That aspirin prevents distant metastasis could account for the early reduction in cancer deaths in trials of daily aspirin vs. 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.”
Study 3. Effect of aspirin on metastases in observational vs. randomized trials. Observational studies showed a 38% reduction in risk of colorectal cancer, matching the 42% reduction shown by randomized trials. Similar matches in risk were found for esophageal, gastric, biliary, and breast cancer.
“Observational studies show that regular use of aspirin reduces the long-term risk of several cancers and the risk of distant metastasis,” they wrote.
Chan and Cook from Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, wrote in an accompanying Comment in The Lancet that Rothwell et al.’s “impressive collection of data moves us another step closer to broadening recommendations for aspirin use,” even as data are awaited from additional clinical trials (NCT01038583 and NCT00501059) and longer-term follow-up of the Women’s Health Study of 39,876 women treated with alternative-day aspirin 100mg over ten years and the Physicians’ Health Study of 22,071 men treated with alternative-day aspirin 325mg over five years. The current analyses do not include these two trials, the world’s largest randomized trials in primary prevention, due to the possibility of differences in the biological effect of alternate-day rather than daily aspirin.
“…future evidence-based guidelines for aspirin prophylaxis can no longer consider the use of aspirin for the prevention of vascular disease in isolation from cancer prevention,” Chan and Cook concluded.