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

Abstract

<div>Abstract<p><b>Purpose:</b> 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).</p><p><b>Patients and Methods:</b> 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.</p><p><b>Results:</b> Patients with NSCLC (<i>n</i> = 155) were randomly assigned to receive vitamin D (<i>n</i> = 77) or placebo (<i>n</i> = 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%, <i>P</i> = 0.04) and OS (91% vs. 48%, <i>P</i> = 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.</p><p><b>Conclusions:</b> In patients with NSCLC, vitamin D supplementation may improve survival of patients with early-stage lung adenocarcinoma with lower 25(OH)D levels. <i>Clin Cancer Res; 24(17); 4089–97. ©2018 AACR</i>.</p></div>