A large, multi-center phase 3 clinical trial has found that high-dose vitamin D3 does not improve outcomes for patients with previously untreated metastatic colorectal cancer when added to standard chemotherapy and bevacizumab. The study, known as SOLARIS (Alliance A021703), was conducted across numerous cancer centers in the U.S. and led by researchers at Dana-Farber Cancer Institute.
The trial enrolled over 450 patients who were randomized to receive either high-dose or standard-dose vitamin D3 in addition to standard chemotherapy plus bevacizumab. The primary endpoint was progression-free survival. After a median follow-up of 20 months, the researchers observed no significant difference in the progression of cancer between the two groups.
Detailed Findings of the SOLARIS Trial
The results, presented at the European Society for Medical Oncology (ESMO) 2024, indicated that the addition of high-dose vitamin D3 did not delay cancer progression more than standard-dose vitamin D3. Kimmie Ng, MD, MPH, a Dana-Farber Cancer Institute author, noted that the findings do not support the use of high-dose vitamin D3 as a standard treatment for metastatic colon cancer.
Interestingly, the researchers observed a potential benefit of high-dose vitamin D3 in patients with left-sided disease, meaning tumors originating in the descending colon, sigmoid colon, or rectum. This subgroup warrants further investigation to determine if there is a specific benefit in this population.
Background and Rationale
The SOLARIS trial was motivated by prior research suggesting that higher blood levels of vitamin D are associated with improved survival in metastatic colorectal cancer. Earlier studies also proposed that adding high-dose vitamin D3 to standard therapy could potentially improve progression-free survival. However, the SOLARIS trial results contradict these earlier findings.
Safety and Tolerability
The study also assessed the safety and tolerability of high-dose vitamin D3. The team reported no additional concerning side effects or toxicities associated with the high-dose regimen, indicating that it is safe to administer in combination with standard chemotherapy and bevacizumab.
Implications for Clinical Practice
Based on the SOLARIS trial results, high-dose vitamin D3 cannot be recommended as a treatment for patients with untreated metastatic colon cancer. While the potential benefit observed in patients with left-sided disease is intriguing, further research is needed to confirm this finding and understand the underlying mechanisms.
The trial highlights the importance of rigorous, randomized clinical trials in evaluating potential cancer therapies, even those based on promising observational data.
