Two studies published in JAMA found conflicting results on the benefits of taking high-dose vitamin D supplementation to improve colorectal cancer (CRC) and gastric cancer survival.
Japanese study finds no benefits of vitamin D
The randomized, double-blind, placebo-controlled AMATERASU trial was conducted at a single university hospital in Japan. Enrollment began in January 2010 and follow-up was completed in February 2018. The study included patients 30 to 90 years of age with stage I-III cancers of the digestive tract. Patients were randomized to receive oral vitamin D supplements (2,000 IU/d; n=251) or placebo (n=166).
Among patients with metastatic CRC, addition of high-dose vitamin D3, to standard chemotherapy resulted in a difference in median PFS that was not statistically significant, but with a significantly improved supportive hazard ratio https://t.co/IWyF0O9OOh
— Nicolas Martínez Velilla (@martinezvelilla) April 11, 2019
The 417 patients (mean age, 66 years) had esophageal cancer (10%), gastric cancer (42%), and CRC (48%). There was 99.8% follow-up over a median 3.5 years (interquartile range, 2.3-5.3 years), and patients were followed for a maximum of 7.6 years.
Relapse or death occurred in 50 patients (20%) in the vitamin D cohort and 43 patients (26%) in the placebo group.
Vitamin D supplementation did not significantly improve relapse-free survival (RFS; primary endpoint): Five-year RFS was 77% with vitamin D and 69% with placebo (hazard ratio [HR] for relapse or death = 0.76; 95% CI, 0.50-1.14; P=0.18). Five-year overall survival (OS) was 82% and 81%, respectively (HR for death = 0.95; 95% CI, 0.57-1.57; P=0.83).
Interesting data but it won’t change my opinion against high dose vitamin D3 https://t.co/an1P6iXVmV
— Andrey Soares (@SoaresAndrey) April 10, 2019
American study observes improved, but not statistically significant, survival
The double-blind, randomized, phase II SUNSHINE trial included 139 patients with advanced or metastatic CRC and was conducted at 11 U.S. academic and community cancer centers between March 2012 and November 2016.
Patients received mFOLFOX6 plus bevacizumab chemotherapy every two weeks and either high-dose vitamin D3 (n=69) or standard-dose vitamin D3 (n=70) daily until disease progression, unacceptable toxicity, or withdrawal.
Higher plasma Vit. D levels have been associated with improved survival in metastatic colorectal cancer (CRC).
In this study it is, but we need more trials to find out if high dose Vit. D added to CRC treatment will be recommendedhttps://t.co/JIzjBS5oMD@EMJGastro
— Elias Said, MD, FACEP (@MdFacep) April 10, 2019
After a median follow-up of 22.9 months among the 139 patients (mean age, 56 years) who completed or discontinued chemotherapy and vitamin D3, the median progression-free survival (primary endpoint) for high-dose vitamin D3 was 13 months (95% CI, 10.1–14.7) versus 11 months with standard-dose vitamin D3 (95% CI, 9.5–14.0; log-rank P=0.07).
There were no significant differences between high- and standard-dose vitamin D3 for tumor objective response rate (58% vs. 63% respectively; 95% CI, −20–100; P=0.27) or OS (median, 24.3 months vs. 24.3 months; log-rank P=0.43).
The most common grade ≥3 adverse events for chemotherapy plus high-dose versus standard-dose vitamin D3 were neutropenia (n=24 [35%] vs. n=21 [31%]) and hypertension (n=9 [13%] vs. n=11 [16%]).
Additional studies are needed to confirm the findings of these studies.