In vivo advantage of combined administration with CPT-11 and 5-fluorouracil in rats.
In vivo effect of a bolus combination with 5-fluorouracil (5-FU) and CPT-11 was studied against experimental rat lung cancer, SLC cells. 5-FU and CPT-11, when administrated individually, showed dose-dependent inhibition against the tumor (ID50, 7.0 mg/kg/day and 16.0 mg/kg/day, respectively). 5-FU synergistically enhanced the sensitivity of the tumor cells to CPT-11 and permitted the administration of approximately a one-third lower dose of CPT-11 to obtain the same inhibition against the tumor cell growth. The ID50 of CPT-11 alone (16.0 mg/kg/day) was reduced to 4.8 mg/kg/day when combined with 5-FU at 2.5 mg/kg. There were no deaths caused by toxicity in the combination group, and for lower doses (less than 4 mg/kg/day) of CPT-11 combined with 2.5 mg/kg/day of 5-FU, all rats showed less than 10% body weight loss at the end of the experiments. When the tumor weights were evaluated by using isoeffect plot analysis, the data points resulting from the combination showed a synergistic interaction between these agents. There was no significant increase of toxicity as assessed by the body weight. The results might support for the use of the combination of 5-FU and CPT-11 in cancer chemotherapy.
Satoh
Hiroaki
H
Division of Respiratory Medicine, Institute of Clinical Medicine, Institute of Basic Medical Sciences, University of Tsukuba, Japan. hirosato@md.tsukuba.ac.jp
Ohtomo
Masao
M
Ishikawa
Hiroichi
H
Kamma
Hiroshi
H
Yamashita
Yuko T
YT
Ohtsuka
Morio
M
Sekizawa
Kiyohisa
K
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D051381:Rats; D014407:Tumor Cells, Cultured
D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin