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.
Showing the most recent 10 out of 600 publications