Delta tocotrienol as a supplement to FOLFOXIRI in first-line treatment of metastatic colorectal cancer. A randomized, double-blind, placebo-controlled phase II study
What this study found
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…
- Study & population
- Randomized, double-blind, placebo-controlled phase II trial at a single center in Denmark.
- Intervention
- Delta-tocotrienol was given orally as capsules at 300 mg three times daily, with each capsule containing 90% delta-tocotrienol and 10% gamma-tocotrienol.
- Key limitation
- This was a small phase II, single-center study, which limits precision and generalizability.
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Open PDFOriginal abstract
Abstract Purpose Triplet chemotherapy might be more effective than doublet chemotherapy in metastatic colorectal cancer (mCRC), but it may also be marked by increased toxicity. To investigate whether δ-tocotrienol, a vitamin E analogue, with possible neuroprotective and anti-inflammatory effects, reduces the toxicity of triplet chemotherapy, we conducted a randomized, double-blind, placebo-controlled trial in mCRC patients receiving first-line 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI). Material and Methods Seventy patients with mCRC were randomly assigned (1:1) to receive FOLFOXIRI plus either δ-tocotrienol or placebo at the Department of Oncology, Vejle Hospital, Denmark. Eligibility criteria were adenocarcinoma in the colon or rectum, age 18–75 years and ECOG performance status 0–1. FOLFOXIRI was given in eight cycles followed by four cycles of 5-fluorouracil. δ-tocotrienol 300 mg or placebo × 3 daily was added during chemotherapy and for a maximum of two years. The primary endpoint was time to hospitalization or death during treatment with chemotherapy. Results Median time to first hospitalization or death was 3.7 months in the placebo group (95% CI 1.93-not reached (NR)), and was NR in the δ-tocotrienol group (95% CI 1.87-NR) with a hazard ratio of 0.70 (95% CI 0.36–1.36). Grade 3–4 toxicities were uncommon in both groups, except for neutropenia, which occurred in 19 patients (58%) in the placebo group and 17 patients (50%) in the δ-tocotrienol group. There were no grade 3 or 4 peripheral sensory neuropathy. In the placebo group, 24 patients (71%) had oxaliplatin dose reductions compared to 17 patients (47%) in the δ-tocotrienol group (p = 0.047). Conclusion The addition of δ-tocotrienol to FOLFOXIRI did not statistically significant prolong the time to first hospitalization or death compared to FOLFOXIRI plus placebo. Toxicity was manageable and not statistically different. There was a statistically significant difference in dose reductions of oxaliplatin pointing to a possible neuroprotective effect of δ-tocotrienol.