SAN FRANCISCO – Patients with metastatic colorectal cancer fared better if they had higher pretreatment levels of vitamin D, according to a prospective analysis from a phase III trial.

On average, the 1,043 patients studied were deficient in vitamin D (25-hydroxyvitamin D), reported lead investigator Dr. Kimmie Ng of the Dana-Farber Cancer Institute, Harvard Medical School, in Boston.

Susan London/Frontline Medical NewsDr. Kimmie Ng

The risks of adverse outcomes fell as vitamin D plasma levels rose. Relative to peers who had levels in the bottom quintile, patients who had levels in the top quintile were 21% less likely to experience progression or death and 35% less likely to die. The findings were consistent across patient subgroups.

“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,” Dr. Ng commented in a press briefing at the annual Gastrointestinal Cancers Symposium sponsored by the American Society of Clinical Oncology.

However, “it’s too early to recommend vitamin D supplementation as a treatment for colon cancer,” she cautioned. “Randomized clinical trials are needed to establish causality and are currently ongoing.”

Press briefing moderator Dr. Smitha S. Krishnamurthi, medical oncologist at University Hospitals Case Medical Center, Cleveland, commented, “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 their outcomes. This study adds to the literature that suggests that vitamin D may have protective effects in preventing colorectal polyps and could help patients with colorectal cancer live longer.”

The observed benefits suggest that this vitamin may slow tumor growth or enhance the effects of chemotherapy, she proposed. “But we really need a randomized, controlled trial of vitamin D supplementation versus placebo to know if vitamin D has anticancer effects,” she agreed. “Until then, patients should have their vitamin D levels checked and undergo supplementation if needed because we know vitamin D is necessary for bone health. But it’s too soon to recommend vitamin D supplementation for anticancer effects.”

Introducing the study, Dr. Ng noted that vitamin D inhibits cell proliferation and angiogenesis, induces cell differentiation and apoptosis, and has anti-inflammatory effects. “Obviously, many of these processes are quite dysregulated in cancer, which led to the hypothesis that perhaps vitamin D has anticancer activity,” she said. Both preclinical research and epidemiologic data have indeed suggested a benefit of higher vitamin D levels in terms of preventing colorectal cancer and improving its outcome.

The investigators studied patients enrolled in CALGB 80405, a randomized, phase III trial of first-line chemotherapy plus biologics. The patients had blood drawn for 25-hydroxyvitamin D measurement and completed questionnaires about diet and lifestyle factors before starting treatment.

Results showed that the median 25-hydroxyvitamin D level in plasma was 17.2 ng/mL in the patients overall, reported Dr. Ng, who disclosed that she has a consulting or advisory role with Genentech/Roche. “This falls within the deficient range, which is typically defined as a 25-hydroxyvitamin D level less than 20 ng/mL,” she noted. When patients were split into quintiles, the median ranged from 8.0 ng/mL in the lowest to 27.5 ng/mL in the highest.

Median overall survival rose across quintiles of 25-hydroxyvitamin D levels (P = .01), from 24.5 months in the lowest to 32.6 months in the highest. After adjustment for age, sex, season, obesity, physical activity, and other potential confounders, the hazard ratio for death also fell significantly with increasing quintile of levels (P = .001). Relative to lowest-quintile peers, patients in the highest quintile had a more than one-third reduction in the risk of death (hazard ratio, 0.65).

Findings were similar for progression-free survival, with the median rising across quintiles (P = .02) from 10.1 months in the lowest to 12.2 months in the highest. The hazard ratio for progression or death fell with rising quintile (P = .01); highest-quintile patients had a more than one-fifth reduction in risk relative to lowest-quintile peers (hazard ratio, 0.79).

“We took great pains to try and control for various lifestyle factors or other indicators of poor health that may potentially explain what we found” to minimize confounding, Dr. Ng commented. “We also tried to address the issue by excluding patients who died very quickly after their blood levels of vitamin D were measured. Those tend to be the patients with the most aggressive disease and who tend to do more poorly. And even after excluding that group of patients, the persistence of the significant relationship between higher levels and survival was seen.”

The research was supported by the National Cancer Institute. Dr. Krishnamurthi had no relevant disclosures. Many of Dr. Ng’s coauthors reported financial ties to multiple companies, including Bristol-Myers Squibb, which funded the CALGB 80405 trial.

Vitamin D appears protective in patients with metastatic colorectal cancer