Life prolonging effect of antitumor agents on postoperative adjuvant therapy in the lung spontaneous metastasis model in mice.
BACKGROUND: We examined the efficacy against pulmonary metastasis of various antitumor agents administered after excision of the primary lesion, which was induced by injection of RENCA murine renal cancer cells. MATERIAL AND METHODS: RENCA cells were implanted into the left kidney of the mice. Nephrectomy of the left kidney bearing the resulting primary tumor was performed on day 10 after implantation, and administration of antitumor agents was started on day 13 [UFT (20 mg/kg), 5'-DFUR (24.6 mg/kg), 5-FU (19 mg/kg), CDDP (7 mg/kg), CPT-11 (50 mg/kg), TNP-470 (30 mg/kg)]. The efficacies of antitumor agents were evaluated by antitumor effect and prolongation of life span. RESULTS: The antitumor effect, which was assayed by growth inhibiting ratio of metastatic tumor in the lung, was significantly in the UFT (55.5%) and TNP-470 (48.7%) treated groups. 5-FU and CDDP exhibited an inhibitory tendency though 5'-DFUR and CPT-11 had no antitumor effect. A significant life-prolonging effect was found for UFT and 5-FU, at a T/C ratio of 160.8% and 125.7%, respectively. The antiangiogenic activity of the agents was examined by counting the number of blood vessels in the metastatic nodules in the lungs. TNP-470 exhibited a strong rate of inhibition of 61.5%, followed by UFT, CDDP and CPT-11, at about 30% inhibition. The in vitro cytotoxicities of 5-FU, SN-38, CDDP and TNP-470 were examined, and 5-FU was observed to have potent cytotoxicity. CONCLUSIONS: These results suggest that both cytotoxicity to tumor cells and antiangiogenic activity were important factors in the life-prolonging effect of antitumor agents in this model, and that UFT, which can be administered orally long-term, may be useful in postoperative adjuvant therapy.