Sova Petr, Mistr Adolf, Kroutil Ales, Zak Frantisek, Pouckova Pavla, Zadinova Marie
Research and Development, PLIVA-Lachema, Brno, Czech Republic.
Anticancer Drugs. 2005 Jul;16(6):653-7. doi: 10.1097/00001813-200507000-00010.
A novel anti-tumor platinum(IV) complex, coded as LA-12, with a bulky adamantylamine ligand displaying oral activity was prepared and its oral activity was evaluated. The murine ADJ/PC6 plasmacytoma and human A2780 ovarian carcinoma tumor model were used to evaluate the in vivo anti-tumor activity of a single dose and also of repeated doses with comparison to the activity of cisplatin and of the platinum(IV) complex satraplatin. The acute toxicity of LA-12 in mice is relatively low (maximum tolerated dose 1000 mg/kg), and the effective dose is comparable to that of cisplatin and higher than that of satraplatin. The therapeutic index derived from this is very high (250). In the human tumor model, two repeated dose schedule regimens were evaluated. LA-12 exerted a significantly higher anti-tumor activity than other substances, i.e. cisplatin and satraplatin, in repeated doses on the murine ADJ/PC6 plasmacytoma tumor model. The dailyx5 repeated dose regimen was selected for further evaluation.
制备了一种新型抗肿瘤铂（IV）配合物，编码为LA-12，其带有庞大的金刚烷胺配体并具有口服活性，并对其口服活性进行了评估。使用小鼠ADJ/PC6浆细胞瘤和人A2780卵巢癌肿瘤模型评估单剂量以及重复剂量的体内抗肿瘤活性，并与顺铂和铂（IV）配合物沙铂的活性进行比较。LA-12对小鼠的急性毒性相对较低（最大耐受剂量为1000 mg/kg），有效剂量与顺铂相当且高于沙铂。由此得出的治疗指数非常高（250）。在人肿瘤模型中，评估了两种重复剂量给药方案。在小鼠ADJ/PC6浆细胞瘤肿瘤模型中，LA-12在重复给药时表现出比其他物质（即顺铂和沙铂）显著更高的抗肿瘤活性。选择每日×5重复剂量给药方案进行进一步评估。
