Does Vitamin D Supplementation Impact Relapse-Free Survival in GI Cancers?

MedicalResearch.com Interview with:
Mitsuyoshi Urashima MD, PhD, MPH
Professor of Molecular Epidemiology
Jikei University School of Medicine
Tokyo, JAPAN

MedicalResearch.com: What is the background for this study?  

Response: Serum levels of vitamin D, increase in response to exposure to sunlight, a vitamin D-rich diet, or vitamin D supplementation. In 1989, the risk of colon cancer was estimated to be 70% lower in people with serum vitamin D levels ≥ 20 ng/mL, compared with those < 20 ng/mL.

In a cohort study, higher vitamin D levels were associated with lower total cancer incidence and lower total cancer mortality, particularly digestive system cancer mortality. However, because of the studies’ observational nature, whether lower levels of vitamin D is merely a precursor to relapse and death or causally related to shorter survival cannot be determined.

To clarify this, a randomized, double-blind, placebo-controlled trial using vitamin D supplement was performed in patients with digestive tract cancer from esophagus to rectum; this is the first trial designed to evaluate the effect of vitamin D on survival of these patients. 

MedicalResearch.com: What are the main findings? 

Response: The 417 patients were randomized to receive oral supplemental capsules of vitamin D (2000 IU/day, n=251) or placebo (n=166) from the first postoperative outpatient visit to until the end of the trial. The 5-year relapse-free survival was 77% vs 69%; hazard ratio for relapse or death, 0.76; 95% CI, 0.50 -1.14; P = 0.18. In a subgroup of patients with serum 25(OH)D levels between 20 and 40 ng/mL at baseline, the 5-year relapse-free survival was 85% vs 71%; Hazard ratio for relapse or death, 0.46; 95%CI, 0.24-0.86; P=0.02; Pinteraction=0.04. The relatively high dose vitamin D did not appear to be associated with frequent adverse events.

MedicalResearch.com: What should readers take away from your report?

Response: 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 in total study population.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Although main conclusion was null as described above, a significant interaction was detected in a subgroup of patients with middle serum vitamin D levels at baseline. Moreover, the cumulative hazard rate of relapse or death was significantly less for the vitamin D group compared with the placebo group in adjustment with age, because patients allocated into vitamin D group were significantly older than placebo by chance.

Since it seemed hard for participants to continue taking supplements during years, decreased adherence may have caused a bias toward null results. In addition, survival curves were overlapped for first 18 months, which may imply that vitamin D is needed to take for at least the first 18 months to exert anti-tumor effects. Thus, we should not totally deny improving effects of vitamin D supplementation on prognosis of patients with cancers, but should keep this type of randomized trials by a greater number of patients with high adherence.

MedicalResearch.com: Is there anything else you would like to add?

Amaterasu emerging from the cave, Ama-no-Iwato, to which she once retreated (painted by Kunisada)- Wikipedia image.jpg
Response:
AMATERASU is the name of famous Japanese sun god, described in Japanese myths. When she was hided inside of rock door, the entire world turned to dark. Because vitamin D is produced under the skin by exposing to sunshine and this is a trial performed in Japan, we named this trial as AMATERASU project.

Any disclosures? The authors do not have any potential conflicts of interests to declare. Both vitamin D and placebo supplements were purchased from Zenyaku Pharmaceutical Co., Ltd., Tokyo, Japan. We have performed this trial without any supports by pharmaceutical or supplemental companies. 

Citation:

Urashima M, Ohdaira H, Akutsu T, et al. Effect of Vitamin D Supplementation on Relapse-Free Survival Among Patients With Digestive Tract CancersThe AMATERASU Randomized Clinical TrialJAMA.2019;321(14):1361–1369. doi:10.1001/jama.2019.2210 

Apr 9, 2019 @ 6:44 pm

 

 

 

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