The potential for clinical application of in vitro assays predicting 5-FU sensitivity in man.
An in vitro assay system to measure the production of phosphorylated nucleotide products of 5-FU by human tumor cytosols is described. Samples from 11 patients with breast cancer treated with 5-FU-containing chemotherapy regimens were assayed. Significant differences were seen in quantitative and qualitative patterns of phosphorylation between samples from chemotherapy responding and nonresponding patients. Both the rate of 5-fluorodeoxyuridylate production and the amount of fluorinated nucleotide triphosphate produced were significantly increased (P less than 0.05) in patients responding to chemotherapy. The latter finding may be attributed to the demonstration of significantly higher nucleoside diphosphate kinase levels in the tumors of responding patients. Further study of this in vitro assay system as a potential system for prospectively predicting clinical response to fluorinated pyrimidines is indicated.
D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002474:Cell-Free System; D003600:Cytosol / Q000378:metabolism; D005467:Floxuridine / Q000378:metabolism; D005468:Fluorodeoxyuridylate / Q000378:metabolism; D005472:Fluorouracil / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D010766:Phosphorylation; D014529:Uridine / Q000031:analogs & derivatives / Q000378:metabolism
D005467:Floxuridine; D005468:Fluorodeoxyuridylate; C001943:5-fluorouridine; D005472:Fluorouracil; D014529:Uridine