# High-Dose Vitamin D Misses Cancer Trial Goal

> In the 455-patient SOLARIS phase 3 trial, adding high-dose vitamin D3 to first-line chemotherapy and bevacizumab did not significantly improve progression-free survival in metastatic colorectal cancer.

_Source: JAMA phase 3 randomized clinical trial, cross-checked against PubMed and ClinicalTrials.gov NCT04094688 · 2026-08-12 · 6 min read · Verified against primary sources_

Canonical: https://iyu.app/e/solaris-high-dose-vitamin-d-colorectal-cancer

## The 60-second version

In SOLARIS, high-dose vitamin D3 added to chemotherapy plus bevacizumab did not significantly improve progression-free survival in previously untreated metastatic colorectal cancer.

**Key points**

- The double-blind phase 3 trial randomized 455 patients and is registered as NCT04094688.
- Median PFS was 11.8 versus 10.3 months, but the prespecified one-sided test was not significant at P=.25.
- Objective response and overall survival were also not significantly different.
- Common severe adverse events were similar, but this does not justify unsupervised high-dose use.

**Verdict.** Do not add high-dose vitamin D expecting a cancer-control benefit from this regimen; deficiency and supplement decisions remain clinical care.

## Full explainer

> **⚑ Caveat:** This trial does **not** support starting high-dose vitamin D without medical supervision or replacing cancer treatment. It tested one add-on strategy in previously untreated metastatic colorectal cancer.


### Result — The primary endpoint was negative

The phase 3 SOLARIS trial randomized **455 patients** with previously untreated metastatic colorectal cancer. Adding high-dose vitamin D3 to first-line chemotherapy plus bevacizumab did **not** significantly improve progression-free survival compared with standard-dose vitamin D3.

- **455** — randomized patients
- **11.8 vs 10.3 months** — median progression-free survival
- **P=.25** — prespecified 1-sided log-rank test

The numerical median was longer in the high-dose group, but that alone does not establish benefit. The prespecified statistical test did not reject the trial's null hypothesis.


### Design — What the two groups received

- **Population:** Previously untreated metastatic colorectal cancer; median age 59; 40% women.
- **Cancer treatment:** mFOLFOX6 or FOLFIRI plus bevacizumab every two weeks in both groups.
- **High-dose arm:** Vitamin D3 8,000 IU daily for 14 days, then 4,000 IU daily.
- **Comparator:** Vitamin D3 400 IU daily.
- **Primary outcome:** Progression-free survival by an unstratified log-rank test.

The registered study, [NCT04094688](https://clinicaltrials.gov/study/NCT04094688), was double-blind, randomized and phase 3. The Alliance for Clinical Trials in Oncology sponsored it with the National Cancer Institute as collaborator.


### Secondary outcomes — Response and survival also showed no clear gain

- **Objective response:** 51% with high dose versus 44% with standard dose; P=.12.
- **Overall survival:** Median 25.6 versus 27.0 months; P=.66.
- **Follow-up:** Median 20 months at the reported analysis.

None of these comparisons was statistically significant. The result therefore does not establish better response, delayed progression or longer survival from the high-dose add-on.


### Safety — No major difference in severe toxicity

Common grade 3 or worse events were similar: neutropenia occurred in 32% versus 30%, and hypertension in 20% versus 23%, for high versus standard dose. The authors found no clinically meaningful difference in common severe events or vitamin D-associated toxicities.

> **i** Similar trial toxicity does not make unsupervised high-dose supplementation safe. Kidney function, calcium balance, other medicines and individual cancer care can change risk.


### Boundary — What the trial does not answer

- It compared **high dose with standard dose**, not vitamin D with no vitamin D.
- It studied a specific first-line metastatic-disease regimen; other stages and treatment combinations were not tested.
- It does not overturn ordinary clinical care for a documented vitamin D deficiency.
- It does not justify replacing chemotherapy, bevacizumab or other proven treatment with supplements.


### Takeaway — How to use the evidence

SOLARIS does not support adding high-dose vitamin D3 with the expectation of prolonging progression-free survival in this setting. Supplement use and deficiency treatment should be discussed with the oncology team.

> A promising phase 2 signal was tested in phase 3 and did not hold up on the primary endpoint.


## Primary sources

- [Telegram post 1406](https://t.me/CNSmydream/1406)
- [JAMA paper](https://doi.org/10.1001/jama.2026.9350)
- [PubMed record](https://pubmed.ncbi.nlm.nih.gov/42545685/)
- [ClinicalTrials.gov registration](https://clinicaltrials.gov/study/NCT04094688)
- [Crossref record](https://api.crossref.org/works/10.1001/jama.2026.9350)

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