Inhibiting Disease Relapse

The AMATERASU Randomized Clinical Trial is a randomized, double-blind, placebo-controlled trial conducted at the International University of Health and Welfare Hospital in Ohtawara, Japan. The purpose of the study was to evaluate whether use of vitamin D3 supplements could improve survival rates for patients with stage I-III digestive tract epithelial carcinoma after surgical resection from the esophagus, stomach, small intestine, colon, or rectum.

The trial enrolled 417 patients aged 30 to 90 years (mean age, 66); 66% were men; patients had esophageal cancer (10%), gastric cancer (42%), or colorectal cancer (48%). Patients were included if they met the histopathological criteria, were not already taking vitamin D supplements, and had no history of urinary tract calculi. Enrollment occurred at their first postsurgical visit to the outpatient clinic. At that point, they were randomly assigned to take a vitamin D3 supplement of 2000 IU every day or placebo. Participants were instructed to take the trial medication daily until the end of the trial. 4

Primary outcomewas relapse-free survival from the first day of taking the study medication until cancer relapse or death from any cause. Secondary outcome was overall survival time to death from cancer or death from any cause.

Chemotherapy Patients with stage II or stage III esophageal cancer received chemotherapy. Patients with stage II or III gastric cancer received postoperative chemotherapy, as did all patients with stage III colorectal cancer.

Vitamin D Radioimmunoassay was used to measure serum levels of 25(OH)D after the study participants began taking the supplements. Trial subgroups had baseline serum 25(OH)D levels of 0 to less than 20 ng/mL, 20 to 40 ng/mL, and more than 40 ng/mL. The researchers only assessed interactions between the low and middle level baseline groups.

For this long-term study, participants were assessed for any cancer relapse with CT and PET scans, MRIs, and other interventions every month for the first 6 months, every 2 months for the second 6 months, and every 3 months after that for 5 years. The surgeon in charge determined follow-ups after 5 years. 4

Results Vitamin D supplementation did not lead to an improvement in relapse-free survival. Twenty percent of those taking vitamin D and 26% of those taking placebo experienced disease relapse or died. Five-year relapse-free survival was 77% for patients in the vitamin D group and 69% for those in the placebo group. The difference is not statistically significant.

Based on these results, the AMATERASU researchers concluded that vitamin D supplementation, compared with placebo, did not result in significant improvement in relapse-free survival at 5 years among patients with digestive tract cancers.

References

1. Lautatzis ME, Sharma A, Rodd C. A closer look at rickets and vitamin D deficiency in Manitoba: the tip of the iceberg. Paediatr Child Health. 2019;24(3):179-184.

2. Miller JW, Harvey DJ, Beckett LA, et al. Vitamin D status and rates of cognitive decline in a multiethnic cohort of older adultsJAMA Neurol. 2015;72(11):1295-1303.

3. Ng K, Nimeiri HS, McCleary NJ, et al. Effect of high-dose vs standard-dose vitamin D3 supplementation on progression-free survival among patients with advanced or metastatic colorectal cancer: the SUNSHINE Randomized Clinical Trial. JAMA. 2019;321(14):1370-1379.

4. Urashima M, Ohdaira H, Akutsu T, et al. Effect of vitamin D supplementation on relapse-free survival among patients with digestive tract cancers: the AMATERASU randomized clinical trial JAMA. 2019;321(14):1361-1369.

5. Cicero G, De Luca R, Dieli F. Progression-free survival as a surrogate endpoint of overall survival in patients with metastatic colorectal cancer. Onco Targets Ther. 2018;11:3059-3063.