A Phase I/II trial of high-dose niacin (vitamin B3) combined with standard chemoradiation in newly diagnosed glioblastoma has produced an early signal that exceeds historical benchmarks by a substantial margin. Of the first 24 evaluable patients, 82.3 percent showed no disease progression at six months, compared with 53.9 percent in the historical Stupp regimen control, an absolute improvement of 28.4 percentage points.
The trial, led by Gloria Roldan Urgoiti and V. Wee Yong at the University of Calgary’s Hotchkiss Brain Institute and Arnie Charbonneau Cancer Institute, is still enrolling toward its target of 48 patients. The interim result exceeded the prespecified futility boundary requiring at least a 20 percent improvement over historical controls, so the study continues to full enrollment.
Why niacin
The rationale is immunological, not directly cytotoxic. Niacin is known to modulate myeloid cell function. In preclinical work, Yong’s group showed that niacin can reactivate tumor-suppressed immune cells in the brain. The companion immunology paper, published in Neurology Neuroimmunology & Neuroinflammation, analyzed peripheral blood from 13 trial participants and found that niacin shifted the immune profile toward an antitumor state: increased memory CD8-positive T cells, increased natural killer cells, decreased immunosuppressive nonclassical monocytes, and elevated levels of the proinflammatory cytokine IL-12p70.
Glioblastoma is notoriously immunologically cold. The tumor microenvironment suppresses immune activity through multiple mechanisms, making checkpoint inhibitors largely ineffective in this cancer. Niacin appears to work upstream, re-engaging the immune system before checkpoint blockade would even be relevant.
Dosing and safety
The trial used a controlled-release oral niacin formulation (NiacinCRT), starting at 500 mg per day and escalating to a maximum tolerated dose of 2,000 mg per day. Patients began niacin seven days before starting standard chemoradiation (radiotherapy plus temozolomide, the Stupp protocol). The 2,500 mg dose caused dose-limiting toxicities: grade 3 thrombocytopenia and grade 3 hyperbilirubinemia, both reversible. Flushing, a well-known side effect of niacin, occurred in 67 percent of patients but was mostly grade 1 and manageable.
No grade 4 or 5 adverse events were reported, and no serious interactions with temozolomide or radiation were observed.
Caveats
This is an interim analysis of an open-label, single-arm Phase I/II trial with no blinding and no randomized control group. The historical benchmark of 53.9 percent six-month progression-free survival comes from the original Stupp trial published in 2005. Patient populations, imaging technology, and supportive care have all changed in the intervening two decades, making historical comparisons inherently unreliable.
The median age was 57, 60 percent were male, and 47 percent had methylated MGMT promoter status, a favorable prognostic marker. The sample is small, and the 95 percent confidence interval around the 82.3 percent estimate was 82.14 to 82.46 percent, which is surprisingly narrow for an interim analysis and may reflect statistical methodology rather than true precision.
Overall survival data have not yet been reported. Progression-free survival at six months is an intermediate endpoint; whether the improvement translates into extended survival remains unknown. The full Phase II target of 48 patients is expected to complete enrollment by late 2026 or early 2027.
What’s next
The trial continues to full enrollment. If the PFS-6M signal holds, the next step would be a randomized controlled trial comparing standard chemoradiation with and without high-dose niacin. The University of Calgary team is also investigating whether niacin could be combined with checkpoint inhibitors or other immunotherapies in glioblastoma.
Niacin is inexpensive, off-patent, and orally administered. If the efficacy signal is confirmed, it could become one of the most accessible adjunct therapies for a cancer that currently has few good treatment options.
Source: Roldan Urgoiti, G., de Robles, P., Tsang, R.Y. et al. A phase I-II study of niacin in patients with newly diagnosed glioblastoma: safety and interim phase II analysis. Journal of Neuro-Oncology 176, Article 101 (2026). DOI: 10.1007/s11060-025-05351-z