Oral 5-FU is a more effective antimetastatic agent than UFT.
5-Fluorouracil (5-FU), a pyrimidine analog, is widely used to treat gastrointestinal and other cancers. In the present study, we compared the efficacy of oral 5-FU and the 5-FU prodrug, uracil plus tegafur (UFT), on liver metastasis in a highly metastatic mouse model. Genetic labeling of the tumor with green fluorescent protein (GFP) along with inexpensive video detectors, positioned external to the mouse, allowed the real-time monitoring of details of tumor growth, metastatic spread and drug response in this mouse model. 5-FU at 10 and 20 mg/kg significantly prolonged the survival time of treated animals compared with untreated controls (p=0.003 for 5-FU, 10 mg/kg; p=0.016 for 5-FU, 20 mg/kg). In contrast, UFT only showed a trend to increase survival (p=0.078). 5-FU at 10 mg/kg substantially prolonged the survival time compared to UFT (p=0.012). 5-FU (10 mg/kg) was also more effective in prolonging survival than Furtulon (5'-deoxy-5-fluorouridine, another 5-FU prodrug) (p=0.042). All control and UFT-treated animals died by day 45. In contrast, at 45 days, 5 out of 8 animals were alive in the 5-FU 10 mg/kg group, which was found to be the best treatment regimen in this study. 5-FU (10 mg/kg)-treated animals had a median survival time of 53 days compared to 26.5 in controls and 33.5 days for UFT. These results suggest the potential clinical superiority of oral 5-FU compared to UFT as an anti-metastatic agent. The data also suggest the lack of clinical need for complex and expensive prodrugs of 5-FU such as UFT.
Wang
Jinwei
J
AntiCancer Inc., San Diego, California 92111, USA.
Yang
Meng
M
Yagi
Shigeo
S
Hoffman
Robert M
RM
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology*; D005467:Floxuridine / Q000494:pharmacology; D005472:Fluorouracil / Q000494:pharmacology*; D049452:Green Fluorescent Proteins; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy / Q000517:prevention & control* / Q000556:secondary*; D008164:Luminescent Proteins / Q000032:analysis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage
D000964:Antimetabolites, Antineoplastic; D008164:Luminescent Proteins; D005467:Floxuridine; D049452:Green Fluorescent Proteins; D005641:Tegafur; D014498:Uracil; D005472:Fluorouracil; C025034:doxifluridine