Delta tocotrienol as a supplement to FOLFOXIRI in first-line treatment of metastatic colorectal cancer. A randomized, double-blind, placebo-controlled phase II study

Randomized, double-blind, placebo-controlled phase II trial at a single center in Denmark. Adults with metastatic or potentially resectable colorectal cancer eligible for first-line FOLFOXIRI and good performance status were enrolled; 36 participants were assigned to the delta-tocotrienol arm.

Delta-tocotrienol was given orally as capsules at 300 mg three times daily, with each capsule containing 90% delta-tocotrienol and 10% gamma-tocotrienol. Treatment was added to first-line FOLFOXIRI and could continue for up to 2 years; the placebo capsule contained olive oil.

Delta-tocotrienol did not significantly improve the primary endpoint of time to first non-planned hospitalization or death. Median time to first hospitalization or death was not reached with delta-tocotrienol versus 3.7 months with placebo, with HR 0.70 (95% CI 0.36-1.36, p=0.29); the 7-month event proportion was 42% versus 57% (p=0.15). Toxicity was broadly similar, with febrile neutropenia in 4 patients in each group and no grade 3 or 4 peripheral sensory neuropathy, but oxaliplatin dose reductions were less frequent with delta-tocotrienol (47% vs 71%, p=0.047). Progression-free survival (9.5 vs 9.2 months; HR 1.08, p=0.77), overall survival (22.3 vs 23.3 months; HR 1.1, p=0.76), and response rate (52% vs 62%) were not improved.

This was a small phase II, single-center study, which limits precision and generalizability. Several outcomes were not statistically significant, and the apparent reduction in oxaliplatin dose reductions was not accompanied by clearer improvements in hospitalization, progression-free survival, overall survival, or response. Follow-up and event counts may have been insufficient to detect modest clinical benefit.