Newly diagnosed metastatic colorectal cancer patients with higher vitamin D levels had better outcomes after treatment with a combination of chemotherapy and targeted therapy. The results of this phase III trial were presented (abstract #507) at a pre-meeting press conference of the upcoming American Society of Clinical Oncology (ASCO) 2015 Gastrointestinal Cancers Symposium, to be held January 15–17 in San Francisco.
The difference in median overall survival between the patients in the highest and lowest quintile of vitamin D levels was 8.1 months. The median overall survival was 32.6 months among patients with the highest vitamin D levels compared with 24.5 months for patients with the lowest vitamin levels (hazard ratio [HR] = 0.67, 95% confidence interval [CI], 0.53–0.86; P = .002).
The median progression-free survival was 12.2 months in the highest vitamin D quintile compared with 10.1 months for those in the lowest vitamin D quintile (HR = 0.80, 95% CI, 0.64–1.01; P = 0.02). There were no significant differences in outcomes based on the type of therapy received. The results were similar regardless of patient characteristics such as KRAS mutation status.
Few patients on the study reported the use of vitamin D supplements.
While it is too early for clinicians to recommend vitamin D as a therapy for colon cancer, maintaining recommended vitamin D levels in general has been shown to benefit overall health.
“Metastatic colorectal cancer patients are frequently deficient in vitamin D. In this study, higher levels of vitamin D in the plasma are associated with both a higher overall survival and progression-free survival,” said lead study author Kimmie Ng, MD, MPH, assistant professor of medicine at Dana-Farber Cancer Institute, at a press conference.
The authors analyzed blood levels of 25-hydroxyvitamin D (vitamin D) among 1,043 newly diagnosed patients enrolled in the CALGB 80405 trial, which compared three different first-line therapies: chemotherapy plus either bevacizumab or cetuximab, or chemotherapy combined with both agents. Patients were divided into five vitamin D level groups.
The median plasma vitamin D level was 17.2 ng/mL. This falls in the deficiency range for vitamin D, which is defined as levels below 20 ng/ml, according to Ng.
African Americans, older patients, and those with lower dietary and supplemental vitamin D intake, ECOG performance status 1 (rather than 0), a higher body-mass index, lower physical activity, and blood draws during the winter and spring had significantly lower levels of vitamin D.
Both epidemiologic and preclinical studies have shown that vitamin D has antitumor activity. Vitamin D has been shown to inhibit cell proliferation and angiogenesis, to induce cell differentiation and apoptosis. Vitamin D also has anti-inflammatory effects. Given to mouse models of colorectal cancer, vitamin D has been shown to result in a lower tumor burden. Additionally, higher vitamin D blood levels are linked to a decreased risk of colorectal cancer as well as improved survival for those diagnosed with the disease.
This is of great interest to patients with colorectal cancer who frequently want to know if there is anything that they can do to better their prognosis, said Smitha S. Krishnamurthi, MD, moderator of the press conference. The work suggests that high vitamin D levels may lead to a slower growing tumor or may enhance the effects of chemotherapy. Still, Krishnamurthi cautioned that these hypotheses need to be formally tested in clinical trials. In the meantime, patients should have their vitamin D levels checked, said Krishnamurthi.
According to Ng, randomized studies are ongoing to investigate whether vitamin D supplements prior to and after a cancer diagnosis are beneficial.