Increased potentiation of 5-fluorouracil induced thymidylate synthase inhibition by 5,10-methylenetetrahydrofolate (arfolitixorin) compared to leucovorin in patients with colorectal liver metastases; The Modelle-001 Trial.

ABSTRACT:

Background

5-Fluorouracil (5-FU) is a cornerstone in treatment of colorectal cancer (CRC) and is usually combined with leucovorin (LV) to enhance the antitumour effect by increase thymidylate synthase (TS) inhibition, the key target enzyme for 5-FU. Arfolitixorin (Arfo) is an active form of the reduced folate, [6 R]-5,10-methylenetetrahydrofolate ([6 R]-MeTHF and in contrast to LV, does not need to be metabolized. The Modelle-001 was designed to explore whether a single intravenous bolus injection of Arfo as compared to LV, together with 5-FU increases the inhibition of TS, levels of folate concentrations and polyglutamylation in CRC liver metastases (CRLM) and liver parenchyma.

Patients and methods

Thirty patients with CRLM received either LV (60 mg/m²) or Arfo (

SUBMITTER: Taflin H 

PROVIDER: S-EPMC11579015 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature