New Investigative Regimens and Cytotoxic Agents in Thoracic Cancers: Gemcitabine and Pemetrexed
July 01, 2004
Several new antimetabolites, administered alone or in combination,are changing the therapeutic landscape for thoracic cancer. Two-drugcombinations involving these newer drugs are becoming the standardof care for non–small-cell lung cancer (NSCLC), largely due to improvementsin survival rates, time to disease progression, and responserates as well as an improved safety profile. Gemcitabine (Gemzar) haselicited considerable interest in this disease, as a combination partnerin chemotherapeutic regimens. Another promising agent is pemetrexed(Alimta), a folate-based inhibitor of thymidylate synthase. In preclinicaldevelopment, pemetrexed both alone and in combination with othercytotoxic agents has exhibited activity across a broad range of tumormodels, including NSCLC and mesothelioma. In clinical trials of patientswith NSCLC, pemetrexed has been an effective, well-toleratedagent that can be used as monotherapy or in combination with otheragents at full dose. In clinical trials of patients with mesothelioma, thecombination of pemetrexed and cisplatin demonstrated a significantimprovement in survival, response, and patient quality-of-life parameters.The principle toxicities of pemetrexed can be minimized by folateand vitamin B12 supplements.