Evidence Explorer / MS-N022

Evidence at a glance

• Population: Previously untreated metastatic colorectal cancer receiving chemotherapy plus bevacizumab.
• Intervention: Vitamin D3 8,000 IU/day for 14 days, then 4,000 IU/day, compared with 400 IU/day.
• Finding: The 455-person SOLARIS phase III trial did not improve progression-free survival, response rate or overall survival.
• Why it matters: This is a material reversal of an encouraging 139-person phase II signal.

What the human evidence found

SOLARIS randomized 455 patients: 228 to high-dose and 227 to standard-dose vitamin D3 with mFOLFOX6 or FOLFIRI plus bevacizumab. Median progression-free survival was 11.8 versus 10.3 months (one-sided log-rank P=.25). Objective response was 51% versus 44% (P=.12), and median overall survival 25.6 versus 27.0 months (P=.66).

The earlier SUNSHINE phase II trial randomized 139 patients and reported median progression-free survival of 13.0 versus 11.0 months; its adjusted hazard ratio favored high dose. The larger confirmatory trial did not reproduce the primary benefit. One phase II report and one phase III report are two trials, not multiple independent confirmations from later analyses.

Limits and what this cannot establish

The result applies to the studied regimen and first-line metastatic setting. It does not answer treatment of documented vitamin-D deficiency, bone health, or other cancers.

Normalizing a deficiency is a separate clinical goal from using high-dose vitamin D as anticancer therapy. The phase III result should prevent biomarker or laboratory arguments from being presented as proof of cancer control.

Safety and practical context

Vitamin D can cause hypercalcemia and kidney injury at excessive exposure, especially with calcium supplements or certain medical conditions. SOLARIS found no clinically meaningful increase in common severe adverse events or vitamin-D-associated toxicities, but trial monitoring is not the same as unsupervised use.

Funding and conflict details are available in the full report but were not fully re-extracted in this appraisal.

Questions for the care team

• Am I treating a measured deficiency, bone-health risk, or trying to influence the cancer?
• What dose and monitoring are appropriate for the actual goal?
• Could calcium, kidney disease, granulomatous disease or another medicine change safety?

Sources checked

• SOLARIS phase III randomized trial (PMID 42545685; published September 1, 2026)
• SUNSHINE phase II randomized trial (PMID 30964527)
• SOLARIS registry record (NCT04094688)

Appraisal date: October 14, 2026. Last literature search: October 14, 2026.

Educational evidence summary, not medical advice. Research regimens describe what was studied; they are not personal prescribing instructions and should not replace cancer treatment or individualized supportive care.