The combined antitumour effect of a new 5-fluorouracil derivative, BOF-A2, and radiation in vivo.
We examined the combined effect of radiation and BOF-A2, a newly developed anti-cancer agent consisting of a masked form of 5-fluorouracil (5-FU) and a potent inhibitor of 5-FU degradation in the liver, on murine tumors. Subcutaneous 8-mm-diameter SCCVII tumours grown in the right thigh of C3H/He mice were used. The mice were locally irradiated with single doses of 10-30 Gy or five fractions of 4 Gy for 5 days, alone or in combination with BOF-A2. BOF-A2 at doses of 30, 75 and 150 mg kg-1 was orally administered 2 h before or immediately after single doses of irradiation, while 15 or 30 mg kg-1 of BOF-A2 was given 1 h prior to each fraction of 4 Gy. The effect of BOF-A2 alone was also examined. The antitumour effect was evaluated by a tumour growth delay assay. BOF-A2 alone showed significant tumour growth delay at all doses used in this study. Combination of BOF-A2 and single or fractionated doses of radiation appeared to produce an additive tumour response, which occurred independently of sequence of the two treatments. The combined effect became greater with the dose of radiation and BOF-A2. In conclusion, BOF-A2 and radiation may be efficiently combined.
Murata
R
R
Department of Radiology, Kyoto University, Japan.
Shibamoto
Y
Y
Miyauchi
S
S
Hirohashi
M
M
Takagi
T
T
Sasai
K
K
Oya
N
N
Hiraoka
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008809:Mice, Inbred C3H; D009374:Neoplasms, Experimental / Q000628:therapy*
D000970:Antineoplastic Agents; C053194:Emitefur; D005472:Fluorouracil