Combination of etanidazole with cyclophosphamide and platinum complexes

摘要: In an effort of improve the therapeutic efficacy and selectivity cyclophosphamide (CTX),cis-diamminedichloroplatinum(II) (CDDP), carboplatin (Carbo), these antitumor alkylating agents were combined with 2-nitroimidazole drug etanidazole (ETA). As revealed by tumor-cell survival assay in FSaIIC murine fibrosarcoma, addition ETA (1 g/kg, i.p.) just prior to i.p. injection various doses resulted increases kill produced each (CTX, 10-fold; CDDP, 20-fold; Carbo, 5-to 15-fold), whereas toxicity bone marrow granulocytemacrophage colony-forming units (CFU-GM) increased only about 0- 3-fold. When CTX was either CDDP or striking killing observed (20- 100-fold across dose range 5- 20-fold Carbo), which supra-additive for additive Carbo as isobologram analysis. The alkylating-agent combinations a further approx. increase both CTX/CDDP CTX/Carbo. This effect greatest at lowest platinum tested case Carbo. Following treatment ETA/CTX/CDDP, CFU-GM 5-fold over that alone, but ETA/CTX/Carbo 10- compared obtained using CTX/Carbo alone. Tumor growth-delay studies significant when given combination ETA. Both ETA/CTX/CDDP tumor growth delays 23 days, represented 1.6-fold those These results suggest could significantly agents, whether they are individually combination.