GTI-2040 + capecitabine

GTI-2040 + capecitabine is a combination regimen consisting of GTI-2040, a 20-mer phosphorothioate antisense oligonucleotide that specifically targets the R2 component (M2 subunit) of ribonucleotide reductase, and capecitabine, an oral prodrug of 5-fluorouracil. The mechanism of action for GTI-2040 involves downregulation of ribonucleotide reductase M2 mRNA and protein, thereby inhibiting DNA synthesis and cell proliferation, sensitizing tumor cells to cytotoxic agents. Capecitabine is a fluoropyrimidine antimetabolite that interferes with DNA synthesis by inhibiting thymidylate synthase after conversion to 5-fluorouracil. The combination was investigated in multiple phase I/II trials for metastatic solid tumors, especially metastatic renal cell carcinoma and metastatic breast cancer, due to preclinical synergy. The resulting regimen aimed to improve cytotoxic efficacy and tumor response, though clinical benefit in some indications was limited and further development may be restricted.

Brand names

capecitabine (as Xeloda; no unique combination brand name known)