Delay in administration of CDDP until completion of AGM-1470 treatment enhances antimetastatic and antitumor effects

The efficacy of cis-diammine dichloroplatinum (CDDP) therapy in combination with continuous administration of angiogenesis inhibitor o-(chloroacetyl-c arbamoyl) fumagillol (AGM-1470) was evaluated experimentally using a transp lantable rat osteosarcoma line previously established in our laboratory. AG M-1470 (2.5 mg/kg body weight/week) was administered by Alzet osmotic pumps for 2 weeks starting from 7 days after tumor inplantation and CDDP (1.25 m g/ kg) was given on days 21 and 24. The number of lung metastatic nodules w as counted and the wet weights of the primary tumors were measured 5 weeks after tumor inplantation. Values with administration of CDDP 3 days after d iscontinuation of AGM-1470 were significantly lower than when the two agent s were coadministered (P < 0.05). This animal model should facilitate optim ization of the timing of combination therapy.