Oral administration of BOF-A2 to rats with lung transplanted tumors results in increased 5-fluorouracil levels.

A new tumor model was developed in which solid Yoshida sarcoma tissue injected intravenously developed into tumors in the lungs of about 30% (13/42) of the inoculated rats. Histological examination revealed that alveoli were occupied with tumor cells and the tumors were similar to those obtained by subcutaneous inoculation. Using this model, the concentrations of 5-fluorouracil (5-FU) in tumor tissue 12 h after oral administration of 3-[3-(6-benzoyloxy-3-cyano-2-pyridyloxycarbonyl)-benzoyl]-1-ethoxy methyl- 5-fluorouracil (BOF-A2, 36 mumol/kg) or a combination of tegafur and uracil in a molar ratio 1 to 4 (UFT, 50 mumol/kg) were found to be 129.8 ng/g and 19.2 ng/g, respectively. Thus, compared to treatment with UFT, BOF-A2 resulted in higher levels of 5-FU in lung tumor tissues. Increased concentrations of 5-FU should have a superior anti-tumor effect and so BOF-A2 merits clinical trial in the treatment of patients with lung cancer.