High Dose Vitamin D Beneficial For Colon Cancer

Phase II SUNSHINE trial results compared effects of low dose and high dose vitamin D supplements and showed higher doses extended CRC PFS from 11 to 13 months, those in the higher dose group were also 36% less likely to have disease progression or death during the 22.9 months follow up. Results were reported at a meeting of the American Society of Clinical Oncology and published in JAMA.

Available data suggests vitamin D has antineoplastic activity, and high levels can help to reduce colorectal cancer risk and improve survival among CRC patients, according to the researchers from the Dana-Farber Cancer Institute. Analysis of Phase III data from a trial investigating chemotherapy plus biological agents in more than 1000 patients with metastatic CRC found those with higher blood levels of 25-hydroxyvitamin D had much better overall survival and PFS.

This randomized study examined whether high dose vitamin D could improve outcomes in patients with previously untreated advanced or metastatic CRC. 139 participants all received standard chemotherapy using mFOLFOX6 plus bevacizumab, who were randomized to receive high dose oral vitamin D3 at 4,000 IU per day or 400 IU per day. Primary endpoint was measured as time from start of chemotherapy and vitamin D to first occurrence of disease progression or death; secondary endpoint included tumour objective response rate defined as the proportion of subjects demonstrating partial or complete responses and overall survival; and change in plasma 25-hydroxyvitamin D levels were measured as another endpoint.

At the start of the trial only 9% of the subjects had sufficient vitamin D levels, over the course of the study those in the low dose group had no substantial change, while those in the high dose group quickly reached and maintained sufficient level.

Increased PFS in the high dose group did not reach statistical significance, but they did exhibit 36% lower hazard ratio for disease progression or death, according to the researchers. High doses of vitamin D appeared to be less effective among obese subjects which may indicate such subsets need even higher doses.

Several potential mechanisms of action may explain this beneficial activity such as vitamin D has been shown to induce apoptosis and counteract aberrant WNT-beta catenin signaling which is critical on colorectal cancer development; and vitamin D has broad anti-inflammatory effects, high levels of 25-hydroxyvitamin D may impact the balance between regulatory and inflammatory T-cell responses.

This study was noted to have several limitations such as it’s small size and inadequate power to detect any effects of high doses on overall survival. That being said it still identifies a safe, cost effective, and easily accessible agent as potential treatment for colorectal cancer that could have large and wide reaching global impact regardless of socioeconomic or country resources.

In the same issue of JAMA a separate paper from Jikei University School of Japan found no benefit of postoperative vitamin D3 supplementation on the relapse free survival of 417 patients with digestive tract cancer in the AMATERASU trial.