High-dose vitamin D didn't slow metastatic colorectal cancer in a phase 3 trial
SOLARIS, a publicly funded phase 3 trial, tested vitamin D3 added to chemotherapy after a promising phase 2 signal. Progression-free survival was 11.8 versus 10.3 months — not a significant difference.
| Group | Value (months) |
|---|---|
| Progression-free — high-dose | 11.8 |
| Progression-free — standard-dose | 10.3 |
| Overall survival — high-dose | 25.6 |
| Overall survival — standard-dose | 27 |
High-dose vitamin D3, added to standard chemotherapy for advanced bowel cancer, did not slow the disease in SOLARIS, a phase 3 randomised trial — a result that fails to confirm an encouraging signal from a smaller earlier study [s1]. The finding is a useful correction to a widespread hope that a cheap, well-tolerated vitamin might meaningfully add to cancer treatment, and it comes from a trial with no commercial interest in the answer [s1].
The signal that prompted it
A phase 2 randomised trial had reported that high-dose vitamin D3, on top of standard treatment, improved progression-free survival compared with a standard dose in metastatic colorectal cancer [s1]. Phase 2 results are hypothesis-generating: they are smaller, and a promising difference can shrink or vanish when tested at full scale. SOLARIS — formally Alliance A021703 — was built to find out whether the signal was real [s1]. It was conducted across the United States through the National Clinical Trials Network and led by the Alliance for Clinical Trials in Oncology with the National Cancer Institute, an academic and publicly funded structure rather than a manufacturer's programme [s1][s2].
What the trial tested
SOLARIS was a double-blind phase 3 trial that enrolled 455 patients with previously untreated metastatic colorectal cancer between October 2019 and December 2022 [s1]. All patients received standard first-line chemotherapy — either mFOLFOX6 or FOLFIRI — plus the antibody bevacizumab every two weeks [s1]. On top of that, they were randomly assigned to high-dose vitamin D3 (8,000 IU daily for 14 days as a loading dose, then 4,000 IU daily) or a standard dose (400 IU daily), continued until the disease progressed, toxicity became intolerable, or the patient withdrew [s1]. The primary endpoint was progression-free survival, the time until the cancer grew or the patient died [s1].
What it found
Among the 455 patients — median age 59 years, 181 (40%) female — median follow-up was 20 months [s1]. Median progression-free survival was 11.8 months (95% confidence interval 10.3 to 13.3) with high-dose vitamin D3 and 10.3 months (95% CI 9.4 to 12.2) with the standard dose, a difference that did not reach statistical significance (one-sided log-rank P = .25) [s1]. The 1.5-month gap sits well within the play of chance for a trial this size [s1].
The secondary endpoints told the same story. The objective response rate — the share of patients whose tumours shrank by a defined amount — was 51% (95% CI 44% to 58%) with high-dose vitamin D and 44% (95% CI 37% to 50%) with the standard dose, not a significant difference (P = .12) [s1]. Overall survival, if anything, ran the other way: a median of 25.6 months with high-dose vitamin D versus 27.0 months with the standard dose (one-sided log-rank P = .66) [s1]. There were no clinically meaningful differences in serious side effects, including grade 3-or-higher neutropenia (32% versus 30%) and hypertension (20% versus 23%), and no excess of vitamin-D-associated toxicities [s1]. The high dose was safe; it simply did not help [s1].
How to read it
SOLARIS is a clean example of why phase 3 confirmation exists. A phase 2 difference that looked worth chasing did not hold up when the question was asked properly, in more patients, with the harder endpoints of response rate and overall survival pointing the same neutral-to-negative way [s1]. Because the trial had no manufacturer sponsor and tested a widely available vitamin, there was no commercial pressure shaping the result — which makes the negative finding, if anything, more trustworthy [s1][s2].
The limits are ordinary. The trial addressed a specific setting — previously untreated metastatic disease, on a specific chemotherapy backbone — and does not speak to vitamin D given to prevent colorectal cancer, or to correcting a genuine deficiency, which are separate questions [s1]. It also tested one dosing schedule; a different regimen cannot be ruled in or out, though the flat response and survival curves give little reason to expect a hidden benefit [s1].
What to watch
The practical takeaway is that adding high-dose vitamin D to first-line chemotherapy for advanced bowel cancer is not supported as a way to extend the time before the disease progresses [s1]. This article describes research and is not medical advice; cancer treatment and supplementation are decisions for treating clinicians.
Sources
- Addition of High-Dose Vitamin D3 to Standard Treatment in Patients With Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703) — JAMA, 2026
- Randomized Double-Blind Phase III Trial of Vitamin D3 Supplementation in Previously Untreated Metastatic Colorectal Cancer (SOLARIS, NCT04094688) — ClinicalTrials.gov
Sources
- Addition of High-Dose Vitamin D3 to Standard Treatment in Patients With Metastatic Colorectal Cancer: The SOLARIS Randomized Clinical Trial (Alliance A021703) — JAMA , August 3, 2026
- Randomized Double-Blind Phase III Trial of Vitamin D3 Supplementation in Previously Untreated Metastatic Colorectal Cancer (SOLARIS, NCT04094688) — ClinicalTrials.gov , September 17, 2019
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