A study in JAMA evaluated whether adding high-dose vitamin D3 to standard chemotherapy improves PFS in patients with advanced or metastatic colorectal cancer.
Adding high-dose vitamin D3 to standard chemotherapy may improve progression-free survival (PFS) in patients with advanced or metastatic colorectal cancer, according to the results of a study published in JAMA.
Based on these findings, vitamin D supplementation represents a potential new treatment option for metastatic colorectal cancer patients that is effective, safe, cost-effective, and globally accessible, according to the authors. “This finding warrants confirmation in a randomized phase 3 trial, which will be activated later this year in 2019,” lead study investigator Kimmie Ng, MD, MPH, director of Clinical Research in Dana-Farber Cancer Institute’s Gastrointestinal Cancer Center, told Cancer Network.
As part of the SUNSHINE Randomized Clinical Trial, researchers enrolled a total of 139 patients (mean age, 56 years; 60 female patients [43%]) between March 2012 and November 2016. All patients received mFOLFOX6 plus bevacizumab chemotherapy every 2 weeks and either high-dose vitamin D3 or standard-dose vitamin D3 daily until disease progression, intolerable toxicity, or withdrawal of consent occurred. Patients in the high-dose arm received a loading dose of 8,000 IU/d of vitamin D3 (two 4,000 IU capsules) for cycle 1 followed by 4,000 IU/d for subsequent cycles. Patients in the standard-dose arm received 400 IU/d of vitamin D3 during all cycles.
With a mean follow-up of 22.9 months, the researchers found there were no significant differences between high-dose and standard-dose vitamin D3 for tumor overall response rate (ORR) (58% vs 63%) or overall survival (median, 24.3 months vs 24.3 months). The most common grade 3 or higher adverse events were neutropenia (35% in the high-dose arm vs 31% in the standard-dose arm) and hypertension (13% for the high-dose arm vs 16% for the standard-dose arm). Fewer episodes of diarrhea were reported in the high-dose arm (1%) compared with the standard-dose arm (12%).
The researchers found the median PFS to be 13 months vs 11 months for chemotherapy plus high-dose vitamin D3 supplementation compared with chemotherapy plus standard-dose vitamin D3, which was not statistically significant. However, the researchers found that a multivariable hazard ratio of 0.64 for PFS or death was statistically significant.
“Although the pre-specified unstratified log-rank P value was 0.07, this actually met the threshold effect that our study was powered to detect,” said Ng. “Our results were not surprising, as they are consistent with preclinical and epidemiologic data that showed a link between higher levels of vitamin D in the blood and improved outcomes in patients with metastatic colorectal cancer.”
Daniel Monti, MD, MBA, who is chair of the Department of Integrative Medicine and Nutritional Sciences at Thomas Jefferson University in Philadelphia, said the relationship between vitamin D and cancer has been of interest to the oncology community for several years, mostly sparked by early observational studies that showed low vitamin D levels in cancer populations.
“The present study attempts to address whether low- or high-dose supplementation has a differential effect on cancer outcomes in a population of metastatic colorectal patients. What they found is a possible efficacy signal for high-dose supplementation,” Monti told Cancer Network. “The study was very well done, and like all studies there are limitations, but the results are quite encouraging.”