Dose reduction without loss of efficacy for 5-fluorouracil and cisplatin combined with folinic acid. In vitro study on human head and neck carcinoma cell lines.
Folinic acid (FA) and cisplatin (CDDP) both potentiate the cytotoxicity of 5-fluorouracil (5-FU). The activity of various drug combinations including 5-FU, CDDP and FA was tested on two human cell lines derived from squamous cell carcinomas of the head and neck. Cytotoxicity was assessed by the semi-automated colorimetric MTT test. The drugs were tested in clinically achievable conditions (concentrations and duration of exposure). The dose response curves for 5-FU (0-100 ng ml-1) associated with FA (10(-7)-10(-5) M) reflected a progressive increase in 5-FU cytotoxicity with increasing FA concentrations. When CDDP (0-5 micrograms ml-1) was associated with 5-FU, CDDP-mediated enhancement of 5-FU cytotoxicity was apparent only when CDDP was given before 5-FU. The triple association CDDP, 5-FU and FA was also tested. In this case, for an identical final cytotoxicity, the presence of FA (10(-6) M) permitted reduction of the 5-FU concentration between 24.2 and 42% and reduction of the CDDP concentration between 13.8 and 72.7%. These observations may be beneficial for the design of more rational therapeutic trials associating CDDP, 5-FU and FA.
Etienne
M C
MC
Centre Antoine-Lacassagne, Nice, France.
Bernard
S
S
Fischel
J L
JL
Formento
P
P
Gioanni
J
J
Santini
J
J
Demard
F
F
Schneider
M
M
Milano
G
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000008:administration & dosage*; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil