CHICAGO – Both aspirin and higher plasma levels of vitamin D appear to be modestly effective in secondary prevention of colorectal cancer, investigators in a large cohort study and a randomized trial report.
Among more than 25,000 Norwegians with colorectal cancer, aspirin use was associated with a 14% improvement in overall survival, and a 25% improvement in colorectal cancer–specific survival, reported Dr. Simer Bains from the Center for Molecular Medicine Norway at the University of Oslo.
A similar protective effect of plasma 25-hydroxy vitamin D (25[OH]D) was seen in a subanalysis of data from the CALGB/SWOG 80405 trial, which showed that patients in the highest quintile had a significantly longer overall survival, compared with patients in the lowest quintile of 25(OH)D. Whether dietary vitamin D supplementation will have the same effect is unknown, however, said Dr. Kimmie Ng of the Dana-Farber Cancer Institute, Boston, at the annual meeting of the American Society of Clinical Oncology.
“If confirmed, these are very important potential interventions as they are low-cost, over-the-counter options that could have substantial implications for treatment of colon cancer patients, commented Dr. Andrew T. Chan of Massachusetts General Hospital, the invited discussant.
The benefits of aspirin in primary prevention of colorectal and other cancers have been well documented, but the role of the “wonder drug” in secondary prevention is unclear, Dr. Bains said.
To see whether the use of aspirin after a colorectal cancer diagnosis could make a difference, she and colleagues drew on Norway’s birth-to-death national medical and prescription databases to identify a retrospective cohort of 25,644 patients with colorectal cancer diagnosed from 2004 to 2011. Of this group 6,109 had documented aspirin exposure, defined as a prescription for more than 6 months of aspirin after a diagnosis of colorectal cancer, and 19,535 did not have documented aspirin exposure.
The aspirin user group had a higher mean age than nonusers (74 vs. 70 years), had slightly more men than women (56% vs. 48% men among nonusers), had a higher proportion of well- or moderately differentiated tumors, and less advanced disease stage at diagnosis.
After 9 years of follow-up, there was no difference between the groups in overall survival on univariate analysis. Suspecting that the lack of effect might be attributable to the aspirin users being an older and potentially more fragile group with more comorbidities than nonusers, the authors performed a multivariate regression analysis controlling for age, gender, tumor stage, differentiation, and other drug use and found a hazard ratio for death with aspirin use of 0.86 (P < .001).
In both univariate and multivariate analysis, aspirin use was associated with improved colorectal cancer–specific survival, with HRs of 0.84 and 0.75, respectively (P < .001 for both).
Dr. Bains acknowledged that the study was limited by the lack of randomization and inability to control for over-the-counter aspirin use.
In a different study, Dr. Ng and colleagues looked at the relationship between plasma 25(OH)D levels in patients with metastatic colorectal cancer enrolled in CALGB/SWOG 80405, which compared the FOLFIRI and FOLFOX regimens plus either cetuximab (Erbitux), bevacizumab (Avastin), or both.
Plasma 25(OH)D levels were measured at baseline by radioimmunoassay before the start of therapy.
The investigators found that among patients in the highest quintile of plasma vitamin D levels, median overall survival was 32.6 months, compared with 24.5 months for patients in the lowest quintile (P = .01).
In a multivariate analysis adjusted for age, sex, race, performance status, chemotherapy backbone regimen, previous adjuvant therapy, RAS mutation status, season of blood draw, region of residency, body mass index and physical activity, the highest levels of 25(OH)D were associated with a 35% improvement in overall survival, compared with the lowest levels (HR 0.65, P for trend = .001).
The investigators found that the association between vitamin D levels and survival persisted across all patient subgroups both before and after adjustment for prognostic factors.
A phase II randomized trial of vitamin D supplementation in patients undergoing adjuvant chemotherapy is currently underway, Dr. Ng noted.
Dr. Chan, the discussant, noted that “vitamin D and aspirin use are among the lifestyle factors most consistently associated with improved outcomes among patients with colorectal cancer in epidemiological studies,” and that “the findings are supported by consistent evidence and biological plausibility.”
The aspirin study was supported by the Research Council of Norway. CALGB/SWOG 80405 was supported by the National Cancer Institute, Southwest Oncology Group, Bristol-Myers Squibb, and Aptuit Inc. Dr. Bains reported no relevant disclosures. Dr Ng reported a consulting or advisory role with several companies, institutional research funding from Genentech/Roche and Pharmaville, and travel expenses from Gilead Sciences. Dr. Chan reported a consulting/advisory role with Bayer Schering Pharma and Pfizer.