Format

Send to

Choose Destination
JAMA. 2019 Apr 9;321(14):1361-1369. doi: 10.1001/jama.2019.2210.

Effect of Vitamin D Supplementation on Relapse-Free Survival Among Patients With Digestive Tract Cancers: The AMATERASU Randomized Clinical Trial.

Author information

1
Division of Molecular Epidemiology, Jikei University School of Medicine, Tokyo, Japan.
2
Department of Surgery, International University of Health and Welfare Hospital, Tochigi, Japan.
3
Department of Pathology, International University of Health and Welfare Hospital, Tochigi, Japan.

Abstract

Importance:

Randomized clinical trials of vitamin D supplementation for secondary prevention in patients with cancer are needed, given positive results of observational studies.

Objective:

To determine whether postoperative vitamin D3 supplementation can improve survival of patients with digestive tract cancers overall and in subgroups stratified by 25-hydroxyvitamin D (25[OH]D) levels.

Design, Setting, and Participants:

The AMATERASU trial, a randomized, double-blind, placebo-controlled trial conducted at a single university hospital in Japan. Enrollment began in January 2010 and follow-up was completed in February 2018. Patients aged 30 to 90 years with cancers of the digestive tract from the esophagus to the rectum, stages I to III, were recruited. Of 439 eligible patients, 15 declined and 7 were excluded after operation.

Interventions:

Patients were randomized to receive oral supplemental capsules of vitamin D (2000 IU/d; n = 251) or placebo (n = 166) from the first postoperative outpatient visit to until the end of the trial.

Main Outcomes and Measures:

The primary outcome was relapse-free survival time to relapse or death. The secondary outcome was overall survival time to death due to any cause. Subgroups analyzed had baseline serum 25(OH)D levels of 0 to less than 20 ng/mL, 20 to 40 ng/mL, and greater than 40 ng/mL; because of small sample size for the highest-baseline-level group, interactions were tested only between the low- and middle-baseline-level groups.

Results:

All 417 randomized patients (mean age, 66 years; male, 66%; esophageal cancer, 10%; gastric cancer, 42%; colorectal cancer, 48%) were included in the analyses. There was 99.8% follow-up over a median 3.5 (interquartile range, 2.3-5.3) years, with maximal follow-up of 7.6 years. Relapse or death occurred in 50 patients (20%) randomized to vitamin D and 43 patients (26%) randomized to placebo. Death occurred in 37 (15%) in the vitamin D group and 25 (15%) in the placebo group. The 5-year relapse-free survival was 77% with vitamin D vs 69% with placebo (hazard ratio [HR] for relapse or death, 0.76; 95% CI, 0.50-1.14; P = .18). The 5-year overall survival in the vitamin D vs placebo groups was 82% vs 81% (HR for death, 0.95; 95% CI, 0.57-1.57; P = .83). In the subgroup of patients with baseline serum 25(OH)D levels between 20 and 40 ng/mL, the 5-year relapse-free survival was 85% with vitamin D vs 71% with placebo (HR for relapse or death, 0.46; 95% CI, 0.24-0.86; P = .02; P = .04 for interaction). Fractures occurred in 3 patients (1.3%) in the vitamin D group and 5 (3.4%) in the placebo group. Urinary stones occurred in 2 patients (0.9%) in the vitamin D group and 0 in the placebo group.

Conclusions and Relevance:

Among patients with digestive tract cancer, vitamin D supplementation, compared with placebo, did not result in significant improvement in relapse-free survival at 5 years.

Trial Registration:

UMIN Identifier: UMIN000001977.

PMID:
30964526
PMCID:
PMC6459116
[Available on 2019-10-09]
DOI:
10.1001/jama.2019.2210
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center