Pemetrexed in the treatment of advanced non-squamous lung cancer

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2009-11, Vol.66 (2), p.141-149
• Main Authors: Rossi, Antonio, Ricciardi, Serena, Maione, Paolo, de Marinis, Filippo, Gridelli, Cesare
• Format: Article
• Language: English
• Subjects: Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biological Products - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - therapy; Cisplatin - therapeutic use; Clinical Trials as Topic; Deoxycytidine - analogs & derivatives; Deoxycytidine - therapeutic use; First-line therapy; Folic Acid Antagonists - therapeutic use; Glutamates - therapeutic use; Guanine - analogs & derivatives; Guanine - therapeutic use; Hematology, Oncology and Palliative Medicine; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - therapy; Maintenance therapy; Medical sciences; Non-squamous carcinoma; NSCLC; Pemetrexed; Pneumology; Pulmonary/Respiratory; SCLC; Second-line therapy; Small Cell Lung Carcinoma - drug therapy; Tumors; Tumors of the respiratory system and mediastinum
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2009.06.006

Abstract Pemetrexed, a new cytotoxic agent, is a potent inhibitor of thymidylate synthase and other folate-dependent enzymes. Firstly, pemetrexed was approved in combination with cisplatin for the treatment of malignant pleural mesothelioma. Successively, it has been studied, as single-agent, in phase II and III trials for second-line therapy of non-small cell lung cancer (NSCLC). Based on these results, pemetrexed has been registered for the treatment of recurrent NSCLC. The next step was to test pemetrexed plus cisplatin versus gemcitabine plus cisplatin, as first-line therapy in advanced NSCLC patients, in a phase III, non-inferiority, randomized trial. This trial reported the pemetrexed plus cisplatin regimen to be not inferior, in terms of activity and efficacy, to the control arm but statistically better tolerated. The role of pemetrexed as maintenance therapy after first-line therapy for advanced NSCLC is currently being evaluated into a phase III trial. The consistency of the results of these recent studies has identified a predictive effect of NSCLC non-squamous histology for pemetrexed. To date, pemetrexed is registered, at the dose of 500 mg/m2 on day 1 of a 3-week schedule, in combination with cisplatin, for first-line therapy and, as single-agent, for second-line treatment of patients with non-squamous NSCLC.This review shows the latest and indicates the future developments of pemetrexed in the treatment of advanced NSCLC patients.