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  • Title: Dual effects of folinic acid in 5-fluorouracil induced killing of human tumor cell lines in vitro.
    Author: Blomgren H, Edler D, Hallström M, Ragnhammar P.
    Journal: Anticancer Res; 1996; 16(5A):2713-7. PubMed ID: 8917376.
    Abstract:
    Folinic acid (leucovorin) is frequently used to augment and modulate the clinical activity of 5-fluorouracil (5-FU) in patients with advanced gastrointestinal (Gl) cancer. However, there are conflicting opinions concerning the optimal doses for these patients, and whether folinic acid modulates the clinical activity of 5-FU in patients with non-Gl cancer. To elucidate these questions, model experiments have been performed on human tumor cell lines in vitro to determine the modulatory activity of various concentrations of folinic acid on 5-FU mediated cytotoxicity using a clonogenic assay. Three cell lines of colon cancer and 3 of glioblastoma origin were exposed to 5-FU alone or with folinic acid for 24 hours. It was observed that relatively low concentrations of folinic acid enhanced the cytotoxicity of 5-FU against the colon cancer lines whereas higher concentrations were less effective. Folinic acid did not enhance the 5-FU mediated killing of the glioma cell lines at any concentration (0.01-100 micrograms/ml). On the contrary, folinic acid seemed to counteract the cytotoxic effect of 5-FU in a reasonably dose-dependent fashion. These results may suggest that the value of folinic acid in the treatment of non-Gl cancer with 5-FU should be evaluated within the framework of controlled clinical trials, and that high doses of folinic acid may not necessarily be more effective than low.
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