- If detected early, colorectal cancer is a curable disease, with about 90% of those diagnosed with stage 1 cancer surviving 5 years from diagnosis.
- However, later stage, or metastatic colorectal cancer has much poorer outlook.
- Studies have shown that vitamin D supplements may help treat metastic colorectal cancer.
- A new phase 3 trial, testing high dose vitamin D3, has found that it is no better than lower doses in improving survival rates, but may benefit people whose primary tumor is in the left colon.
Early stage colorectal cancer can usually be treated with surgery, with or without chemotherapy, and has a 5-year survival rate of
But when colorectal cancer has spread, or metastasized beyond the bowel, only around 14% of people with this diagnosis survive longer than 5 years from diagnosis.
Early research has shown that vitamin D3 supplementation, alongside chemotherapy, may help prevent the disease from progressing, and enhance survival rates from metastatic colorectal cancer.
Following these encouraging results, the SOLARIS randomized clinical trial, published in
Although the higher dose enhanced survival in people with tumors on the left colon, overall there was no significant difference in survival between those on the higher and lower D3 doses.
Kimmie Ng, MD, MPH, professor of medicine at Harvard Medical School, Associate Chief of the Division of Gastrointestinal Oncology at the Dana-Farber Cancer Institute in Boston, MA, lead author of the study, told Medical News Today:
“Unfortunately, the primary results of the study did not show statistically significant differences in progression-free survival between patients randomized to high-dose vitamin D compared to low-dose vitamin D. There were also no statistically significant differences in the response rates of these patients’ cancers or in overall survival.”
The study may not have found a benefit of high-dose vitamin D3, but Ketan Thanki, MD, a board-certified colorectal surgeon who specializes in benign and malignant disease of the colon, rectum, and anus with the MemorialCare Todd Cancer Institute at Long Beach Medical Center in Long Beach, CA, and was not involved in this study, welcomed its publication.
“Studies with ‘negative’ results are equally important as, if not more important than, studies with ‘positive’ results. This is because without negative results, the medical literature becomes skewed toward positive findings, leading to overestimation of how promising treatments are, wasting of resources on dead end hypotheses, and potentially repetition of experiments already answered in unpublished files,” Thanki told MNT.
“A negative trial like SOLARIS can close an open question, redirect resources, and tell us something true about biology,” he added.
In the double-blind, multicenter, phase 3 clinical trial, 455 patients with metastatic colorectal cancer were randomly allocated to receive either high-dose or standard dose vitamin D3 every 14 days alongside the standard chemotherapy treatment for their disease.
“My first thought upon reading this paper was that current standard of care does not include routine supplementation, even at low dose, of vitamin D3 for patients undergoing chemotherapy for metastatic colorectal cancer. As a result, are we missing an effect of any degree of supplementation — whether low or high — by comparing low dose to high dose and not including an arm that includes no supplementation at all, unless a patient is already deficient at baseline or high risk for bone loss during chemotherapy?”
– Ketan Thanki, MD
Following withdrawal of some patients whose disease had progressed, the 212 patients in the high-dose group received 8,000 international units/day (IU/d) of vitamin D3 as a loading dose at the start, followed by 4,000 IU/d for subsequent 14-day cycles, and 209 patients in the standard dose group received 400 IU/d throughout the trial.
At entrance to the trial, patients had a median age of 59 years, and a median
In the high dose group, 38.2% had their primary tumor in the left colon, 35.1% in the right colon and 21.5% in the rectum. For the standard-dose group, 39.8% had the primary tumor in the left colon, 33.6% in the right colon, and 20.4% in the rectum.
The researchers followed up participants until the primary end point, which was progression-free survival — time from randomization to first occurrence of documented disease progression, or death. Throughout the trial researchers monitored participants’ plasma vitamin D levels.
Median progression-free survival in the high dose group was 11.8 months, and in the standard dose group, 10.3 months. In the high-dose group, 120 people died, and in the standard dose group, there were 112 deaths.
There was no significant difference between the 2 groups for either progression-free survival, or overall survival rates.
However, high-dose vitamin D3 did appear to benefit one group of patients, as Ng explained: “In a subgroup of patients who have left-sided primary colorectal tumors, there did seem to be a benefit favoring those who were randomized to high-dose vitamin D, with significant improvements in progression-free survival compared to those patients with left-sided tumors who received low-dose vitamin D.”
Those on the high-dose had a median 13.8 months of progression-free survival, whereas for those on the standard dose it was 10.2 months.
However, Ng cautioned that this finding was “hypothesis-generating and exploratory, and definitely requires further confirmation in future studies, but is intriguing given that we do know that left-sided colorectal tumors are different from right-sided colorectal tumors.”
Thanki agreed that the finding needed further research: “When you look at multiple subgroups, you increase the chance of finding a false positive result by chance alone. The overall trial was negative, which means any subgroup signal needs to be treated skeptically.”
“This is a great starting point to ask a question if left and right colon cancers respond differently to D3 supplementation, but is by no means an answer that they do. We know that right and left-sided colon cancers have very different tumor biology, so it is not a stretch to suggest that they may, and perhaps further studies will demonstrate that D3 is beneficial for one and not the other.”
