Dual effects of folinic acid in 5-fluorouracil induced killing of human tumor cell lines in vitro.
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.
Karolinska Hospital, Stockholm, Sweden.
H
H
Blomgren
D
D
Edler
M
M
Hallström
P
P
Ragnhammar
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D003110:Colonic Neoplasms; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D005909:Glioblastoma; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil