The findings of two randomized clinical trials indicate that vitamin D supplementation does not improve clinical outcomes in patients with advanced or metastatic colorectal cancer or gastrointestinal cancer. The results of theand trials were published in JAMA.
The SUNSHINE clinical trial was a double-blind, multicenter, phase 2 study that included 139 patients with metastatic or unresectable advanced colorectal cancer. Participants were randomized to receive either high-dose (8000 IU/day for 2 weeks and 4000 IU/day afterward) or standard-dose (400 IU/day) oral vitamin D3 that was given concomitantly with standard chemotherapy.
The primary outcome measured was median progression-free survival, while overall survival was measured as a secondary endpoint.
“Participants continued to receive treatment until disease progression, intolerable toxicity, or decision to discontinue treatment,” wrote Kimmie Ng, MD, MPH, of the Dana-Farber Cancer Institute in Boston and her colleagues.
The AMATERASU clinical trial was a double-blind, placebo-controlled study of 417 patients with digestive tract cancers conducted at a single center in Japan. Participants were randomized to receive either oral vitamin D (2000 IU/day) or placebo over a maximum duration of 7.6 years.
The primary outcome measured was relapse-free survival (time to cancer relapse or death); overall survival (time to death of any cause) was also included as a secondary endpoint.
“Safety outcomes comprised bone fractures, urinary stones, serious events requiring admission, and new (de novo) cancer,” Mitsuyoshi Urashima, MD, of Jikei University in Tokyo, Japan, wrote with his colleagues.
After analysis, the results of both trials were found to be comparable because the adjusted measures for progression- or relapse-free survival were similar. In addition, both studies showed no differences in overall survival.
Dr. Ng and her colleagues reported that there was a statistically nonsignificant rise in median progression-free survival in participants given high-dose versus standard dose vitamin D3 (13 vs. 11 months, respectively; P = .07), according to results from the SUNSHINE study. The overall survival was the same in both arms (median survival, 24.3 months; P = .43).
Dr. Urashima and his colleagues reported that there was no significant improvement in relapse-free survival in patients treated with vitamin D versus those treated with placebo (hazard ratio, 0.76; 95% confidence interval, 0.50-1.14; P = .18), according to results from the AMATERASU study. In addition, no benefit was seen for overall survival (HR, 0.95; 95% CI, 0.57-1.57).
With respect to safety, neither study reported an increase in toxicity from vitamin D supplementation, and a possible benefit of reduced diarrhea was seen in the SUNSHINE study. Given the preliminary nature of these results, further confirmatory studies that include longer follow-up periods and improved measures of survival are necessary.
“These findings warrant further evaluation in a larger multicenter randomized clinical trial,” Dr. Ng and her colleagues wrote.
“Vitamin D supplementation did not improve relapse-free survival among patients with digestive tract cancer,” Dr. Urashima and his colleagues concluded.
The SUNSHINE clinical trial was supported by grant funding from the National Institutes of Health’s National Cancer Institute. Additional funding was provided by the Gloria Spivak Faculty Advancement Award, Friends of Dana-Farber Cancer Institute Award, Project P Fund, Consano, Pharmavite, and Genentech.
The AMATERASU clinical trial was supported by funding from the Japan-Supported Program for the Strategic Research Foundation at Private Universities, the International University of Health and Welfare Hospital, and the Jikei University School of Medicine.
The authors of both studies reported multiple associations with pharmaceutical companies.
SOURCE: Ng K et al. JAMA. 2019 Apr 9. ; Urashima M et al. JAMA. 2019 Apr 9. .