THE COMBINED ANTITUMOR 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 devel oped 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 muri ne tumours. Subcutaneous 8-mm-diameter SCCVII tumours grown in the rig ht thigh of C3H/He mice were used. The mice were locally irradiated wi th single doses of 10-30 Gy or five fractions of 4 Gy for 5 days, alon e 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) L 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 dela y assay. BOF-A2 alone showed significant tumour growth delay at all do ses used in this study. Combination of BOF-A2 and single or fractionat ed doses of radiation appeared to produce an additive tumour response, which occurred independently of sequence of the two treatments. The c ombined effect became greater with the dose of radiation and BOF-A2. I n conclusion, BOF-A2 and radiation may be efficiently combined.