Supplementing chemotherapy with high doses of vitamin D might delay progression of metastatic colorectal cancer, scientists from Dana-Farber Cancer Institute determined in a study of 139 patients.
Patients in the high-dose group experienced a median delay of 13 months before their disease worsened, compared with a median delay of 11 months in the low-dose group, a delay that was not statistically significant.
However, patients in the high-dose vitamin D group were 36 percent less likely to suffer disease progression or death during the 22.9 months following treatment—and that finding is compelling enough to warrant further study.
The trial was too small to determine whether patients who took high-dose vitamin D had a higher overall rate of survival.
“To our knowledge, this study is the first completed randomized clinical trial of vitamin D supplementation for treatment of advanced or metastatic colorectal cancer,” said Dr. Kimmie Ng, director of clinical research in Dana-Farber's Gastrointestinal Cancer Center, and corresponding author of the SUNSHINE study. Ng’s statement was included in a press release from the Dana-Farber Cancer Institute.
The initial findings were reported at the 2017 meeting of the American Society of Clinical Oncology. Those results, along with additional data, were published in the April 9 issue of JAMA.
Elizabeth L. Barry, associate professor of epidemiology at Dartmouth College's Geisel School of Medicine, cautioned in an editorial that the findings were preliminary: “Confirmatory trials are needed, ideally with longer follow-up to obtain better estimates of effects on survival, as well as biological measurements to clarify underlying mechanisms,” Marcia Frellick of Medscape.com quoted from the same issue of JAMA.
“The results of our trial suggest an improved outcome for patients who received vitamin D supplementation, and we look forward to launching a larger trial to confirm these exciting and provocative findings,” said Dr. Charles Fuchs, senior author of the study and director of the Yale Cancer Center. Fuchs’ statement was included in the Dana-Farber Cancer Institute’s press release.
Prompted by the “very encouraging” results of the SUNSHINE clinical trial, a larger clinical trial is being planned to start in the United States later this year. Frellick reported that the bigger study will include 400 patients being treated at hundreds of sites.
“If that study is also positive, we think vitamin D should be part of standard treatment of patients with metastatic colon cancer,” Ng told Frellick.
Vitamin D, which is necessary for bone health, is made in the body through a chemical reaction dependent on sun exposure and is contained in some foods.
In laboratory studies, vitamin D has demonstrated anti-cancer properties such as triggering programmed cell death, inhibiting cancer cell growth and reducing metastatic potential. Prospective observational studies have linked higher blood levels of vitamin D with a lower risk of colorectal cancer and improved survival of patients with the disease, but those studies could not prove that vitamin D was the cause.
The SUNSHINE trial—conducted from March 2012 through November 2016 (with follow-up through September 2018)—randomized 139 patients with previously untreated metastatic colorectal cancer. One group took pills containing 4,000 international units (IU) of vitamin D per day along with standard chemotherapy, while the other group took 400 units (about the dose found in a multivitamin) along with chemotherapy, which was given every two weeks.
For this phase of the trial, researchers enrolled patients at 11 academic and community centers across the United States; they all received standard chemotherapy. Participants had a mean age of 56. Of the 139 patients, 60 were women.
Patients in the high-dose vitamin D group initially took 8,000 IU a day for 14 days, then 4,000 IU a day thereafter. The low or standard-dose vitamin D group took 400 IU daily during all cycles. All patients were asked not to take any other vitamin D or calcium supplements during the trial period.
The researchers also sampled patients’ blood to measure changes in the levels of 25-hydroxyvitamin D. The tests showed that only 9 percent of patients in the clinical trial had sufficient vitamin D at the beginning of treatment. During the study, patients receiving low doses of vitamin D had no substantial change in their levels, while those in the high-dose group soon reached the vitamin D-sufficient range and maintained it.
The benefit of high-dose vitamin D appeared to be lower in patients who were obese, and those whose tumors contained a mutated KRAS gene, suggesting “that certain subsets of patients may need even higher doses of vitamin D for anti-tumor activity,” the researchers said. They cautioned, however, that high doses of vitamin D shouldn’t be taken except within the context of a clinical trial.
The study and its findings are “extremely important,” Ng said, because “it identifies a cost-effective, safe, and easily accessible agent as a potential new treatment for metastatic colorectal cancer. This could therefore potentially have a large and wide-reaching impact globally, regardless of a patient’s socioeconomic status or a country’s resources.”
The research was supported by National Cancer Institute grants P50CA127003, R01CA205406, and R01CA118553; a Gloria Spivak Faculty Advancement Award; a Friends of Dana-Farber Cancer Institute Award; the Project P Fund; Consano, Pharmavite LLC, and Genetech.
In a financial statement, Ng reports grants from National Cancer Institute, grants and non-financial support from Pharmavite, grants from Genentech, and grants from Consano during the conduct of the study; grants and non-financial support from Pharmavite, personal fees from Genentech, personal fees from Lilly, grants from Gilead Sciences, grants and personal fees from Tarrex Biopharma, personal fees from Bayer, personal fees from Seattle Genetics, grants from Celgene, and grants from Trovagene outside the submitted work.
New Hope Network staff member Victoria Camron contributed to this report.
Source: Dana-Farber Cancer Institute