Vitamin D Supplementation and Survival of Patients with Non-small Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial

Clin Cancer Res. 2018 Sep 1;24(17):4089-4097. doi: 10.1158/1078-0432.CCR-18-0483. Epub 2018 Jul 17.


Purpose: Higher serum 25-hydroxyvitamin D (25(OH)D) levels are reportedly associated with better survival in early-stage non-small cell lung cancer (NSCLC). Therefore, whether vitamin D supplementation can improve the prognosis of patients with NSCLC was examined (UMIN000001869).Patients and Methods: A randomized, double-blind trial comparing vitamin D supplements (1,200 IU/day) with placebo for 1 year after operation was conducted. The primary and secondary outcomes were relapse-free survival (RFS) and overall survival (OS), respectively. Prespecified subgroup analyses were performed with stratification by stage (early vs. advanced), pathology (adenocarcinoma vs. others), and 25(OH)D levels (low, <20 ng/mL vs. high, ≥20 ng/mL). Polymorphisms of vitamin D receptor (VDR) and vitamin D-binding protein (DBP) and survival were also examined.Results: Patients with NSCLC (n = 155) were randomly assigned to receive vitamin D (n = 77) or placebo (n = 78) and followed for a median of 3.3 years. Relapse and death occurred in 40 (28%) and 24 (17%) patients, respectively. In the total study population, no significant difference in either RFS or OS was seen with vitamin D compared with the placebo group. However, by restricting the analysis to the subgroup with early-stage adenocarcinoma with low 25(OH)D, the vitamin D group showed significantly better 5-year RFS (86% vs. 50%, P = 0.04) and OS (91% vs. 48%, P = 0.02) than the placebo group. Among the examined polymorphisms, DBP1 (rs7041) TT and CDX2 (rs11568820) AA/AG genotypes were markers of better prognosis, even with multivariate adjustment.Conclusions: In patients with NSCLC, vitamin D supplementation may improve survival of patients with early-stage lung adenocarcinoma with lower 25(OH)D levels. Clin Cancer Res; 24(17); 4089-97. ©2018 AACR.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / diet therapy*
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology
  • Aged
  • CDX2 Transcription Factor / genetics
  • Carcinoma, Non-Small-Cell Lung / diet therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • DNA-Binding Proteins / genetics
  • Dietary Supplements
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diet therapy*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Polymorphism, Genetic
  • Prognosis
  • Receptors, Calcitriol / genetics
  • Transcription Factors / genetics
  • Vitamin D / administration & dosage*
  • Vitamin D / adverse effects
  • Vitamin D / analogs & derivatives*


  • CDX2 Transcription Factor
  • CDX2 protein, human
  • DBP protein, human
  • DNA-Binding Proteins
  • Receptors, Calcitriol
  • Transcription Factors
  • VDR protein, human
  • Vitamin D
  • 25-hydroxyvitamin D

Associated data

  • UMIN-CTR/UMIN000001869