Combination effect of an angiogenesis inhibitor agm-1470 with 5'-deoxy-5-fluorouridine, and with hormonal drugs in dmba-induced rat mammary-tumors.

AGM-1470, a potent angiogenesis inhibitor, is known to suppress the growth of solid tumors in vivo. In this study, we investigated the combination effect of AGM-1470 with 5'-deoxy-5-fluorouridine (5'-DFUR) which is converted to 5-FU by pyrimidine nucleoside phosphorylase, with tamoxifen (TAM), and with medroxyprogesterone acetate (MPA) in dimethylebenz(a)-anthracene (DMBA) induced rat mammary tumors. Since 5'-DFUR and MPA are noted to have antiangiogenic activity, this combination study might imply not only the addition to chemotherapeutic or hormonal drugs for the angiogenesis inhibitor but also the combination of two angiogenesis inhibitors. The combination of AGM-1470 (20 mg/kg) with 5'-DFUR (200 mg/kg) and with TAM (0.8 mg/kg) markedly suppressed the tumor growth. There was a significant difference in the suppression of tumor growth between the combination group and either drug alone group (p<0.01). No statistical combination effect between AGM-1470 and MPA was found, however MPA markedly reversed the body weight loss induced by AGM-1470. This result will be informative for clinical studies on the combination effect of AGM-1470.