High-dose vitamin D boosts PFS in metastatic colorectal cancer
Supplementation with high doses of vitamin D slows down disease progression in patients with colorectal cancer, the phase II SUNSHINE trial has shown.
“Patients seemed to do better on high-dose vitamin D. I am really excited with the results as this is the first randomized trial of vitamin D as a colorectal cancer therapy,” said lead investigator Dr Kimmie Ng of the Dana Farber Cancer Institute in Boston, Massachusetts, US. “Definitely, a phase III trial is warranted.”
The primary endpoint of median progression-free survival (PFS) was longer in the high-dose group (13.3 months) vs the low-dose group (11.2 months).This translates into a difference of 2 months in PFS. Of note, there was a 31 percent reduction in the relative risk for disease progression in the high-dose group (hazard ratio [HR], 0.69; p=0.04]. Disease control rate was 96 percent in the high-dose group vs 84 percent in the low-dose group (p=0.05). [ASCO 2017, abstract 3506]
Patients in the high-dose group received a loading dose of 8000 IU/day of vitamin D3 orally for 2 weeks followed by 4000 IU/day. Those in the low-dose group received a standard vitamin D3 dose of 400 IU/day. Median follow-up was 16.9 months in the high-dose group and 17.9 months in the low-dose group.
All had metastatic disease and received standard treatment with mFOLFOX6 (folinic acid [leucovorin], fluorouracil, and oxaliplatin) plus bevacizumab. The number of chemotherapy cycles were similar for both the high-dose and low-dose groups; primary tumour locations were comparable. Both groups were compliant with their vitamin D regimen.
Of note, more patients in the high-dose arm were able to undergo surgery after chemotherapy (11 vs 6), but this did not reach statistical significance.
Most patients in the trial were from New England, the others from the US. Discussant Dr Andrea Cercek of the Memorial Sloan Kettering Cancer Center in New York City, US said geography may have played a role. “In New England, there is a little less sunshine than other parts of America.”
Vitamin D3 is produced when the skin is exposed to the sun. Vitamin D3 then binds to a protein, which then ships the vitamin to the liver. Other sources of vitamin D3 are fatty fish or fortified foods, and supplements.
The study raised a question about the existing levels of vitamins D in patients included in the trial. “It’s not known if these patients were deficient by US standards,” Cercek said.
A phase III trial in patients with metastatic disease may shed light to the long-debated issue of vitamin D supplementation in colorectal cancer, Cercek concluded.