Antitumor activity and metabolism of BOF-A2, a new 5-fluorouracil derivative, with human cancers xenografted in nude mice

Antitumor activity of BOF-A2, a new 5-fluorouracil (5-FU) derivative, was evaluated with human gastric (H-111 and H-81), colorectal (H-143), pancreatic (H-48) and breast (H-31) cancers xenografted in nude mice. Twenty-five consecutive oral administration of BOF-A2 at 17.5 to 30 mg/kg over 4 weeks caused marked inhibition or regression (over 92% of inhibition rate) to the growth of H-81, H-143 and H-31 cancers. Moreover, BOF-A2 effected to both H-111 and H-48 which have low sensitivity to 5-FU and its known derivatives. Throughout the experiments, the mice seemed to tolerate the consecutive administration of BOF-A2 without severe toxicity. When BOF-A2 was given orally, 5-FU levels in the blood of mice was notably durative for a long time as compared to 5-FU and UFT. Furthermore, 5-FU levels in the tumor tissue tended to increase and persist much more than those in the blood. This maintenance and persistence of objective level of 5-FU in the blood would be concluded to produce a high antitumor effect of BOF-A2 against human cancers xenografted in nude mice.