cisplatin + methoxyamine + pemetrexed

The combination of cisplatin, methoxyamine, and pemetrexed is an investigational treatment regimen being studied primarily for advanced solid tumors and malignant pleural mesothelioma. This combination therapy works through multiple mechanisms to target cancer cells. Cisplatin is a well-established chemotherapy drug that binds to DNA at the N7 position of purine, forming adducts that alter DNA activity and trigger apoptosis. Pemetrexed is an antifolate antineoplastic agent that blocks substances needed for cancer cell DNA synthesis and repair, preventing cancer cells from multiplying. Methoxyamine hydrochloride (TRC102) is a novel biochemical inhibitor of the base excision repair (BER) pathway that enhances the cytotoxic effects of chemotherapy by binding to DNA and making it a substrate for topoisomerase II, which then cleaves these sites to produce strand breaks that cause cellular apoptosis. Clinical trials have investigated this combination therapy, including a Phase I/II trial (NCT02535312) studying the side effects and optimal dosing of methoxyamine when given with cisplatin and pemetrexed for treating advanced solid tumors or mesothelioma. The hypothesis is that methoxyamine may make tumor cells more sensitive to cisplatin and pemetrexed, potentially providing better treatment outcomes than standard therapies. The combination is typically administered intravenously in a medical office or infusion center setting, with pemetrexed usually given once every 21 days as part of a treatment cycle. Patients receiving this combination often require supportive medications including folic acid supplements, vitamin B12 injections, and sometimes corticosteroids to reduce side effects. This combination represents an approach to overcome resistance to standard treatments and potentially improve outcomes for patients with difficult-to-treat cancers, particularly those who have not responded well to previous therapies.

Brand names

Alimta

Other names

methoxyamine hydrochloride (for TRC102)platinum-based chemotherapy (class for cisplatin)