raltitrexed + doxorubicin

Raltitrexed + doxorubicin is a combination chemotherapy regimen used in the treatment of advanced gastric cancer. Raltitrexed (Tomudex) is a folate analog that directly inhibits thymidylate synthase, leading to DNA fragmentation and cell death. It is transported into cells via a reduced folate carrier and extensively polyglutamated intracellularly, enhancing its inhibitory power and duration. Doxorubicin is an anthracycline antibiotic that works through multiple mechanisms including DNA intercalation, topoisomerase II inhibition, and generation of free radicals. This combination has been investigated in phase I clinical trials for advanced or metastatic gastric cancer, where patients received 2.5-3.5 mg/m² raltitrexed followed by 30-60 mg/m² intravenous doxorubicin every 3 weeks. The combination was generally well tolerated with no dose-limiting toxicities observed at full single-agent doses of 3.0 mg/m² raltitrexed and 60 mg/m² doxorubicin. A dose-finding study by Bjarnason et al. recommended doses of 3 mg/m² raltitrexed and 60 mg/m² doxorubicin every 3 weeks, with a response rate of 20% in gastric cancer patients and median overall survival of 6.8 months.