TY - JOUR
T1 - Intake and biomarkers of folate and folic acid as determinants of chemotherapy-induced toxicities in patients with colorectal cancer
T2 - a cohort study
AU - Kok, Dieuwertje E.
AU - van Duijnhoven, Fränzel J.B.
AU - Lubbermanb, Floor J.E.
AU - McKay, Jill A.
AU - van Lanen, Anne-Sophie
AU - Winkels, Renate M.
AU - Wesselink, Evertine
AU - van Halterend, Henk K.
AU - de Wilt, Johannes H.W.
AU - Ulrich, Cornelia M.
AU - Ulvik, Arve
AU - Ueland, Per Magne
AU - Kampman, Ellen
N1 - Funding information: This work has been funded by the Wereld Kanker Onderzoek Fonds (WKOF) as part of the World Cancer Research Fund International grant programme [IIG_FULL_2021_023]. D.E. Kok is supported by a grant of the Dutch Research Council [016.Veni.188.082]. The COLON study was supported by Wereld Kanker Onderzoek Fonds (WKOF) & World Cancer Research Fund International (WCRF International) as well as by funding [2014/1179, IIG_FULL_2021_022, IIG_FULL_2021_023] obtained from the Wereld Kanker Onderzoek Fonds (WKOF) as part of the World Cancer Research Fund International grant programme; Alpe d’Huzes/Dutch Cancer Society [UM 2012-5653, UW 2013-5927, UW 2015-7946]; and ERA-NET on Translational Cancer Research (TRANSCAN: Dutch Cancer Society [UW2013- 6397, UW2014-6877] and the Netherlands Organization for Health Research and Development (ZonMw), the Netherlands) and the Regio Deal Foodvalley [162135].
PY - 2024/2/1
Y1 - 2024/2/1
N2 - Background: Capecitabine is an oral chemotherapeutic drug showing antitumor activity through inhibition of thymidylate synthase, an enzyme involved in folate metabolism. There are concerns about the high intake of certain vitamins, and specifically folate, during chemotherapy with capecitabine. Whether folate or folic acid, the synthetic variant of the vitamin, impact treatment toxicity remains unclear. Objective: We studied associations between intake and biomarkers of folate as well as folic acid and toxicities in patients with colorectal cancer (CRC) receiving capecitabine. Methods: Within the prospective COLON (Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that influence recurrence, survival, and quality of life) cohort, 290 patients with stage II to III CRC receiving capecitabine were identified. Dietary and supplemental intake of folate and folic acid were assessed at diagnosis and during chemotherapy using questionnaires (available for 280 patients). Plasma folate and folic acid levels were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) and were available for 212 patients. Toxicities were defined as toxicity-related modifications of treatment, including dose reductions, regimen switches, and early discontinuation. Associations of intake and biomarkers of folate and folic acid with toxicities were determined using Cox proportional hazards regression adjusted for age and sex. Results: In total, 153 (53%) patients experienced toxicities leading to modification of capecitabine treatment. Folate intake and plasma folate levels were not associated with risk of toxicities. However, use of folic acid-containing supplements during treatment (hazard ratio (HR) 1.81 and 95% confidence interval (CI) 1.15-2.85) and presence of folic acid in plasma at diagnosis (HR 2.09, 95% CI: 1.24, 3.52) and during treatment (HR 2.31, 95% CI: 1.29, 4.13) were associated with an increased risk of toxicities. Conclusions: This study suggests a potential association between folic acid and capecitabine-induced toxicities, providing a rationale to study diet-drug interactions and raise further awareness of the use of dietary supplements during oncological treatment. Clinical trial details: This trial was registered at clinicaltrials.gov as NCT03191110.
AB - Background: Capecitabine is an oral chemotherapeutic drug showing antitumor activity through inhibition of thymidylate synthase, an enzyme involved in folate metabolism. There are concerns about the high intake of certain vitamins, and specifically folate, during chemotherapy with capecitabine. Whether folate or folic acid, the synthetic variant of the vitamin, impact treatment toxicity remains unclear. Objective: We studied associations between intake and biomarkers of folate as well as folic acid and toxicities in patients with colorectal cancer (CRC) receiving capecitabine. Methods: Within the prospective COLON (Colorectal cancer: Longitudinal, Observational study on Nutritional and lifestyle factors that influence recurrence, survival, and quality of life) cohort, 290 patients with stage II to III CRC receiving capecitabine were identified. Dietary and supplemental intake of folate and folic acid were assessed at diagnosis and during chemotherapy using questionnaires (available for 280 patients). Plasma folate and folic acid levels were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) and were available for 212 patients. Toxicities were defined as toxicity-related modifications of treatment, including dose reductions, regimen switches, and early discontinuation. Associations of intake and biomarkers of folate and folic acid with toxicities were determined using Cox proportional hazards regression adjusted for age and sex. Results: In total, 153 (53%) patients experienced toxicities leading to modification of capecitabine treatment. Folate intake and plasma folate levels were not associated with risk of toxicities. However, use of folic acid-containing supplements during treatment (hazard ratio (HR) 1.81 and 95% confidence interval (CI) 1.15-2.85) and presence of folic acid in plasma at diagnosis (HR 2.09, 95% CI: 1.24, 3.52) and during treatment (HR 2.31, 95% CI: 1.29, 4.13) were associated with an increased risk of toxicities. Conclusions: This study suggests a potential association between folic acid and capecitabine-induced toxicities, providing a rationale to study diet-drug interactions and raise further awareness of the use of dietary supplements during oncological treatment. Clinical trial details: This trial was registered at clinicaltrials.gov as NCT03191110.
KW - folate
KW - folic acid
KW - dietary supplements
KW - diet
KW - biomarker
KW - colorectal cancer
KW - chemotherapy
KW - toxicity
KW - apecitabine
KW - capecitabine
UR - http://www.scopus.com/inward/record.url?scp=85181050934&partnerID=8YFLogxK
U2 - 10.1016/j.ajcnut.2023.11.023
DO - 10.1016/j.ajcnut.2023.11.023
M3 - Article
SN - 0002-9165
VL - 119
SP - 294
EP - 301
JO - The American Journal of Clinical Nutrition
JF - The American Journal of Clinical Nutrition
IS - 2
ER -
