Pemetrexed in the treatment of advanced non-small-cell lung cancer: a review of the clinical data.
Pemetrexed is a novel multitargeting antimetabolite that has first-line and second-line activity against non-small cell lung cancer (NSCLC). Phase II studies have shown significant efficacy and a favorable toxicity profile of the combination of pemetrexed plus platinum as first-line therapy for NSCLC. Second-line activity against NSCLC was demonstrated in a phase III trial comparing single-agent pemetrexed with docetaxel; in that trial, survival was comparable between these agents but side effects were significantly less for patients who received pemetrexed. Pemetrexed is also an active agent against mesothelioma. A phase III trial comparing pemetrexed plus cisplatin with cisplatin alone showed for the first time a regimen that improves survival in this disease and led to FDA approval of pemetrexed in combination with cisplatin for mesothelioma. As a radiosensitizer, pemetrexed has been well-tolerated when given concurrent with chest radiation, and a phase I study is under way assessing its tolerability in combination with carboplatin in this setting. Pemetrexed is clearly a useful agent in the treatment of thoracic malignancies, and is worthy of further study in combination with other drugs having novel mechanisms of action.
Zinner
Ralph G
RG
Department of Thoracic/Head & Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, 77030, USA. rzinner@mdanderson.org
Herbst
Roy S
RS
D000971:Antineoplastic Combined Chemotherapy Protocols; D016190:Carboplatin / Q000008:administration & dosage* / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D002986:Clinical Trials as Topic; D005971:Glutamates / Q000008:administration & dosage* / Q000494:pharmacology; D006147:Guanine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed
D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin; D002945:Cisplatin