PHASE I TRIAL OF LY231514 W/ IRINOTECAN

这是一项LY 231514联合伊立替康治疗转移性癌症患者的I期研究。 本剂量探索研究将为未来研究中LY 231514和伊立替康的给药提供建议。 LY-231514是一种叶酸抗代谢药，主要作用机制是抑制胸苷酸合成酶（TS），这是一种叶酸依赖性酶，催化DNA合成所需的过程。 它在体外具有高度的细胞毒性。 盐酸伊立替康是植物生物碱喜树碱的半合成衍生物，是一类新型细胞毒性药物，可抑制维持DNA构象和功能所必需的拓扑异构酶I。 本研究联合这些药物的总体目标是开发一种安全的联合治疗方案，用于在相关肿瘤中进行评价，确定MTD、定量和定性毒性，评估血浆药代动力学，并记录抗肿瘤活性。

This is a Phase I study of LY231514 in combination with irinotecan therapy in patients with metastatic cancer. This dose finding study will provide a recommendation for the dosing of LY231514 and irinotecan in future studies. LY-231514 is a folate antimetabolite with the primary mechanism of action the inhibition of the enzyme thymidylate synthase (TS), a folate dependent enzyme which catalyzes the process necessary for DNA synthesis. It is highly cytoxic in vitro. Irinotecan hydrochloride is a semisynthetic derivative of the plant alkaloid camptothecin and is one of new class of cytotoxic agents which inhibit the enzyme topoisomerase I, necessary for maintaining the conformation and functionality of DNA. The overall goal of this study in combining these agents is to develop a safe combination regimen for evaluation in relevant tumors, determining the MTD, the quantative and qualitative toxicities, assessing plasma pharmacokinetics, and documenting the antitumor activity.