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

Autor: Raunkilde L; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Denmark.; Danish Colorectal Cancer Center South, Vejle Hospital, Denmark.; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark., Hansen TF; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Denmark.; Danish Colorectal Cancer Center South, Vejle Hospital, Denmark.; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark., Havelund BM; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Denmark.; Danish Colorectal Cancer Center South, Vejle Hospital, Denmark., Thomsen CB; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Denmark.; Danish Colorectal Cancer Center South, Vejle Hospital, Denmark., Rafaelsen SR; Danish Colorectal Cancer Center South, Vejle Hospital, Denmark.; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.; Department of Radiology, Vejle Hospital, University Hospital of Southern Denmark, Denmark., Lindebjerg J; Danish Colorectal Cancer Center South, Vejle Hospital, Denmark.; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.; Department of Pathology, Vejle Hospital, University Hospital of Southern Denmark, Denmark., Jensen LH; Department of Oncology, Vejle Hospital, University Hospital of Southern Denmark, Denmark.; Danish Colorectal Cancer Center South, Vejle Hospital, Denmark.; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.
Jazyk: angličtina
Zdroj: Acta oncologica (Stockholm, Sweden) [Acta Oncol] 2023 Sep; Vol. 62 (9), pp. 1066-1075. Date of Electronic Publication: 2023 Aug 30.
DOI: 10.1080/0284186X.2023.2249225
Abstrakt: 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.
Databáze: MEDLINE
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