Pemetrexed in the treatment of advanced non-squamous lung cancer.
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/m(2) 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.
Rossi
Antonio
A
Division of Medical Oncology, S.G. Moscati Hospital, Contrada Amoretta, 83100 Avellino, Italy.
Ricciardi
Serena
S
Maione
Paolo
P
de Marinis
Filippo
F
Gridelli
Cesare
C
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001688:Biological Products / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000628:therapy; D002945:Cisplatin / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D005493:Folic Acid Antagonists / Q000627:therapeutic use; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000628:therapy; D000068437:Pemetrexed; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D001688:Biological Products; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D003841:Deoxycytidine; D006147:Guanine; D002945:Cisplatin; D000093542:Gemcitabine