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 v arious antitumor agents administered after excision of the primary les ion, which was induced by injection of RENCA murine renal cancer cells . Materials and methods. RENCA cells were implanted into the left kidn ey of the mice. Nephrectomy of the left kidney bearing the resulting p rimary tumor was performed on day 10 after implantation, and administr ation of antitumor agents was started on day 13 [UFT (20 mg/kg), 5'-DF UR (24.6 mg/kg), 5-FU (19 mg/kg), CDDP (7 mg/kg), CPT-II (50 mg/kg), T NP-470 (30 mg/kg)]. The efficacies of antitumor agents were evaluated by antitumor effect and prolongation of life span. Results: The antitu mor 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-II 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 w as 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-II, at about 30% inhibition. The in vitro cytotoxicities of 5-FU, SN-38, CDDP and TNP-470 were examine d and 5-FU was observed to have potent cytotoxicity. Conclusions: Thes e results suggest that both cytotoxicity to turner cells and antiangio genic activity were important factors in the life-prolonging effect of antitumor agents in this model, and that UFT which can be administere d orally long-term, may be useful in postoperative adjuvant therapy.