BACKGROUND AND PURPOSE:

• A precursor of activated vitamin D, 25-hydroxyvitamin-D (25[OH]D) may suppress cancer growth
  • Previous cohort studies show association VitD levels and a lower risk of GI cancer
  • RCTs conflicting
• Urashima et al. (JAMA, 2019) sought to determine if
  • Postoperative VitD₃ increases overall survival in patients with digestive tract cancers subgroup stratification based on 25(OH)D levels

METHODS:

• AMATERASU trial
  • Randomized, double-blind, placebo-controlled (RCT)
• Participants
  • Patients with digestive tract cancers
  • Ages 30 to 90 years
  • Cancer stage I to III
• Intervention
  • Oral supplemental vitamin D capsules (2000 IU/d)
  • Placebo
  • Administered from first outpatient visit post-operation until the end of trial
• Primary outcome
  • Relapse-free survival time to relapse or death
• Secondary outcome
  • Overall survival time to death due to any cause
• 25(OH)D serum level analysis
  • Baseline serum level subgroups
    • <20 ng/mL
    • 20-40 ng/mL
    • >40 ng/mL
  • Note: Highest baseline level group had a small n, so interactions limited to low and middle baseline groups

RESULTS:

• 417 patients
  • Supplemental vitamin D: 251 | placebo: 166
  • Mean age: 66 years | 34% were female
  • Esophageal 10% | Gastric 42% | Colorectal 48% | Small Bowel 0.5%
  • Disease stage I 44% | II 26% | III 30%
• Follow up: 99.8% over a median of 3.5 years
  • Interquartile range: 2.3-5.3
  • Maximal follow-up: 7.6 years
• Relapse or death
  • Vitamin D: 20% (50 individuals)
  • Placebo: 26% (43 individuals)

Outcomes

• Death from any cause
  • Vitamin D: 15% (37 individuals)
  • Placebo: 15% (25 individuals)
• Primary outcome: 5-year relapse-free survival – no statistical difference
  • Vitamin D: 88% 
  • Placebo: 69%
  • Hazard ratio (HR) for relapse or death: 0.76 (95% CI, 0.50-1.14; P = .18)
• Secondary outcome: 5-year overall survival – no statistical difference
  • Vitamin D: 82%
  • Placebo: 81%
  • HR for death: 0.95 (95% CI, 0.57-1.57; P = .83)
• 5-year relapse free-survival for middle baseline serum 25(OH)D levels 20-40 ng/mL
  • Vitamin D: 85%
  • Placebo: 71%
  • HR for relapse or death: 0.46 (95% CI, 0.24-0.86; P = .02)
• Fractures
  • Vitamin D: 1.3% (3 individuals)
  • Placebo: 3.4% (5 individuals)
• Urinary stones
  • Vitamin D: 0.9% (2 individuals)
  • Placebo: 0% (0 individuals)
• No differences found when comparing
  • Men vs women | Age ≤65 years vs >65 years BMI <25 vs ≥25 | Site of cancer: | Disease stage | Adenocarcinoma vs nonadenocarcinoma

CONCLUSION:

• Vitamin D does not impact overall relapse-free survival in individuals with GI cancers

Learn More – Primary Sources:

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

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