Tegafur-uracil is a safe alternative for the treatment of colorectal cancer in patients with partial dihydropyrimidine dehydrogenase deficiency: a proof of principle

Abstract

Objective: The objective of this study was to evaluate the safety of using tegafur-uracil (UFT) in colorectal cancer patients with partial dihydropyrimidine dehydrogenase (DPD) deficiency.

Patients and methods: The study included five colorectal cancer patients who presented with acute toxicity (grades 3 and 4) after being given the first cycle of chemotherapy using 5-fluorouracil. The DPD deficiency was confirmed by gene sequencing. After a full recovery from all side effects, we changed the regimen to UFT (300 mg/m(2)/day) associated with leucovorin (90 mg/day) for 21 days, with an empirical dose reduction of at least 10% in the first cycle.

Results: We prospectively analysed 22 UFT cycles in 5 patients. We did not observe any episodes of grade 3 or 4 toxicity. The predominant toxicities were of grades 1 and 2 (nausea, vomiting and diarrhoea).

Conclusion: Here, we demonstrate a complete absence of severe toxicity in all patients and cycles analysed. We believe that UFT is a safe alternative for the treatment of patients with partial DPD deficiency.

Keywords: colorectal neoplasms; dihydropyrimidine dehydrogenase deficiency; drug toxicity; fluorouracil; tegafur; uracil.

Figure 1.

Grade of toxicity after the first cycle of 5-fluorouracil (A), after the first UFT cycle (B) and the worst toxicity presented in all cycles of UFT (C).