Folinic Acid (CF)/5-Fluorouracil (FUra) Combinations in Advanced Gastrointestinal Carcinomas

The introduction of CF promises to be an important step towards a more successful treatment of colorectal cancer. CF (CH2-H4Pte Glu) is a biochemical modulator of fluoropyrimidine action and enhances cytotoxicity of FUra and FUDR in vitro and in vivo. CF/FUra combinations have been investigated in a number of clinical trials. Objective response rates of 30% – 40% were reproducibly achieved indicating a superiority of CF/FUra over FUra alone (1–7). However, inspite of these promising results the benefit of chemotherapy in colorectal cancer remains undetermined with respect to patient survival which is influenced by factors leading to a wide range of spontaneous survival time of patients with advanced colorectal cancer, e.g. stage of disease, tumor load, and particularly rate of tumor growth at time of diagnosis. If tumor growth rates are not determined prior to therapy treatment outcome might be biased by slowly or rapidly proliferating tumors and not necessarily reflect drug activity. Also, lack of tumor growth during observation period might be misinterpreted as antineoplastic effect (“no change”,“stabilisation”).