Modelle 001, TS-inhibition in Colorectal Liver Metastases Comparing Arfolitixorin and Calciumfolinate

Arfolitixorin (\[6R\] 5,10-methylenetetrahydrofolate) is a folate based biomodulator designed to replace leucovorin. Arfolitixorin is the key active metabolite of leucovorin (LV) and does in contrast to LV not require enzymatic metabolic activation. In clinical practice, LV is administered in the form of Calciumfolinate. A hypothesis is therefore that patients which are not capable of metabolizing LV could have a better antitumoral effect with Arfolitixorin administration. The antitumoural effect could be measured as inhibition of the enzyme thymidylate synthase, an enzyme essential for DNA synthesis. Primary objective The primary objective is to compare the properties of Arfolitixorin and Calciumfolinate together with 5-fluorouracil (5-FU) on thymidylate synthase (TS) (i.e. measured as thymidylate synthase inhibition) in tumour and adjacent liver tissue in patients with liver metastases from colorectal cancer receiving a peroperative intravenous administration of Arfolitixorin or Calciumfolinate. Secondary objectives To study safety in terms of adverse events and laboratory measurements; haematology and clinical chemistry. To explore differences in pharmacokinetics of folates and folate metabolites in plasma. To study gene expression in tumour and adjacent hepatic tissue and its correlation to tissue concentration. To investigate the relation between the levels of deoxyuridine (dU) in plasma with the amount of TS inhibition in tumour tissue, in order to evaluate dU as a surrogate marker for TS-inhibition. Study population: Thirty adult patients with colorectal cancer and liver metastases, indicated for surgical removal will be randomised.