Fluorouracil-Based Chemotherapy in Patients with Gastrointestinal Malignancies: Influence of Nutritional Folate Status on Toxicity

Abstract

This study aimed to prospectively evaluate the potential influence of folate status on the toxicity induced by 5-fluorouracil (5-FU)-based chemotherapy in patients with gastrointestinal tumors. 105 patients with colorectal, pancreatic or gastric cancer were entered into the study. Treatment regimens consisted of bolus 5-FU/leucovorin or infusional 5-FU combined with cisplatin. Baseline homocysteine, vitamin B₁₂olic acid serum levels were determined in all patients. Univariate and multivariate logistic regression models were used to identify predictive factors for toxicity. Univariate analysis showed a significant association between older age, low BSA, gastric/pancreatic cancer and treatment with 5-FU/cisplatin and the incidence of grade 3-4 hematological toxicity, and between female sex, low BSA and gastric/pancreatic cancer and the incidence of severe non-hematological toxicity. Variables that retained independent prognostic value in the multivariate model were tumor type, chemotherapy schedule and BSA for both hematological and non-hematological toxicities. Baseline homocysteine, vitamin B₁₂ or folate status were not significant predictors of any kind of toxicity either according to univariate or multivariate analysis. This study failed to demonstrate a significant association between a patient's nutritional folate status and the toxicity induced by fluoropyrimidinebased chemotherapy in a cohort of patients with various gastrointestinal malignancies.

Keywords:

• Fluoropyrimidines
• folate
• gastrointestinal cancer
• homocysteine
• toxicity
• vitamin B12