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High vitamin D levels linked to improved outcomes in metastatic colorectal cancer
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High concentrations of vitamin D were associated with improved OS and PFS in patients with metastatic colorectal cancer who received chemotherapy and biologic therapies, according to results of a prospective observational study presented at the Gastrointestinal Cancers Symposium.
“Vitamin D is known to inhibit cell proliferation and angiogenesis, it induces cell proliferation and apoptosis, and [it] also has anti-inflammatory effects,” Kimmie Ng, MD, MPH, assistant professor of medicine at Dana-Farber Cancer Institute and Harvard Medical School, said during a press conference. “Many of these processes are quite dysregulated in cancer, which led to the hypothesis that perhaps vitamin D has anti-cancer activity.”
Kimmie Ng
Previous research has indicated that vitamin D supplements decreased the intestinal tumor burden in mouse models. Prospective observational studied have demonstrated that high vitamin D levels are associated with a decreased risk for colorectal cancer as well as improved survival in patients with colorectal cancer, Ng said.
“Our previous work has also demonstrated that metastatic colorectal cancer patients are commonly deficient in vitamin D, and this is concerning if we believe that higher levels may be beneficial,” Ng said.
Ng and colleagues evaluated baseline 25-hydroxyvitamin D levels — the best indicator of vitamin D levels — in 1,043 patients with metastatic colorectal cancer who were enrolled on the CALGB 80405 study. Patients received chemotherapy plus bevacizumab (Avastin, Genentech), cetuximab (Erbitux, Bristol-Myers Squibb and Eli Lilly) or both.
The median plasma 25-hydroxyvitamin D plasma level in the study population was 17.2 ng/mL (range, 2.2-72.7), which is below the 20 ng/mL level considered for deficiency.
Lower 25-hydroxyvitamin D levels were more common in patients who were older, those who were black, those who had lower dietary and supplemental vitamin D intake, and those who had higher BMI and lower physical activity. Patients who had an ECOG performance status of 1 vs. 0 and those who had blood drawn during the winter and spring also had lower 25-hydroxyvitamin D levels.
Researchers divided patients into quintiles of 25-hydroxyvitamin D levels. Patients in the lowest quintile had a median 25-hydroxyvitamin D level of 8 ng/mL, whereas patients in the highest level had a median 25-hydroxyvitamin D level of 27.5 ng/mL.
Patients with the highest quintile of 25-hydroxyvitamin D levels had significantly prolonged OS compared with patients who had the lowest quintile of 25-hydroxyvitamin D levels (32.6 months vs. 24.5 months). Analyses adjusted for pathological and clinical prognostic factors indicated higher 25-hydroxyvitamin D levels were associated with a reduction in the risk for death (HR=0.65; 95% CI, 0.51-0.83).
PFS also was significantly improved in patients in the highest vs. lowest quintile of 25-hydroxyvitamin D levels (12.2 vs. 10.1 months; HR=0.79; 95% CI, 0.63-0.99).
The association between higher 25-hydroxyvitamin D levels and improved survival was seen across all patient subgroups, Ng said.
“Metastatic colorectal cancer patients are frequently deficient in vitamin D, and higher levels of vitamin D in plasma are associated with significantly longer OS and PFS,” Ng said. “Randomized clinical trials are needed to establish causality and are currently ongoing.”
For more information:
Ng K. Abstract #507. Presented at: Gastrointestinal Cancers Symposium; Jan. 16-18, 2015; San Francisco.
Disclosure: The study was funded by the NCI. Ng reports consultant/advisory roles with, travel expenses from and research funding from CBPartners, Genentech/Roche, Gilead Sciences, Havas Life Metro, McCann Regan Campbell Ward and Pharmavite LLC. See the study for a list of the other researchers’ relevant financial disclosures.
Perspective
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Smitha A. Krishnamurthi, MD
This study will be of great interest to patients with colorectal cancer, who frequently want to know if there is anything they can do besides chemotherapy to improve outcomes. This study adds to the literature that suggests that vitamin D may have a protective effect in preventing colorectal polyps and could help patients with colorectal cancer live longer. Of note, patients with the highest vitamin D levels had the longest survival, and their PFS also was improved, suggesting that high vitamin D levels may lead to a slower growing tumor or could enhance the effects of chemotherapy. We really need a randomized controlled trial of vitamin D supplementation vs. placebo to know if vitamin D really has anti-cancer effects. Until then, patients should have their vitamin D levels checked and undergo vitamin D supplementation if needed because we know vitamin D is needed for bone health. But it’s too soon to recommend vitamin D supplementation for anti-cancer effects.
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