Vitamin D3 supplementation may improve relapse-free survival for certain digestive tract cancers

1. This post-hoc analysis of the AMATERASU randomized clinical trial found that, for digestive tract cancer patients with positive p53-immunoreactivity, 2000 IU/day vitamin D3 supplementation resulted in significantly improved relapse-free survival at 5 years. 

Evidence Rating Level: 1 (Excellent)

Recent meta-analyses of randomized clinical trials have found that daily vitamin D3 supplementation benefited cancer mortality. In this posthoc subgroup analysis of the AMATERASU randomized, double-blind, placebo-controlled clinical trial, patients with digestive cancers were followed up for a median of 3.5 years to compare the effects of vitamin D3 (2000 IU/day) supplementation with placebo. A participant pool of 392 patients included 183 patients with colorectal cancer, 170 patients with gastric cancer, 37 with esophageal cancer, and 2 with small bowel cancer. Within the subgroup of 80 patients who were found to be p53 immunoreactive, a 5-year relapse occurred in 16.7% of vitamin D group patients compared to 53.8% of the patients in the placebo group (p = .005). Relapse-free survival at 5 years was also significantly higher in the vitamin D group (13 patients, 80.9%) than the placebo group (1 patient, 30.6%; HR, 0.27; 95% CI, 0.11-0.61; p = .002; estimated power > 0.99). The difference remained significant after adjusting for relative levels of p53, age, and history of cardiovascular disease. However, in patients who were not p53 reactive, findings were no longer significant, with 22.2% and 21.1% of patients experiencing relapse or death in the vitamin D and placebo groups, respectively. Relapse-free survival was essentially identical in both groups (HR, 1.09; 95% CI, 0.65-1.84). This study suggests potential benefits for vitamin D supplementation in digestive tract cancer patients who are p53-antibody positive (serum and immunohistochemical tissue staining), but could not support this hypothesis for patients who were not p53-antibody positive. While there are some limitations to this study, results are encouraging and future research on both vitamin D supplementation as well as targeted p53-antibody therapies should be explored. 

Click to read the study in JAMA Network Open

Image: PD

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