Pemetrexed in advanced non-small-cell lung cancer.
BACKGROUND
Current therapeutic options for advanced non-small-cell lung cancer (NSCLC) yield relatively modest improvements in survival leading to an ongoing search for new active treatment agents. In the past decade, pemetrexed has had an increasingly established role in the treatment of advanced NSCLC in both first- and second-line settings.


METHODS
Currently available published data on mechanism of action, pharmacokinetics, safety and efficacy of pemetrexed in the treatment of advanced NSCLC are described. Peer-reviewed publications on the development of pemetrexed and its clinical use in NSCLC were reviewed (1995 - 2009).


RESULTS
Pemetrexed is a multitargeted antifolate cytotoxic agent. Key Phase II and Phase III trials are described that have shown pemetrexed's efficacy in both the first- and second-line treatment of advanced NSCLC. The efficacy of pemetrexed seems to vary between squamous and nonsquamous histologies. Possible reasons for this are explored. Additionally, the potential role of pemetrexed in maintenance therapy is discussed.


CONCLUSIONS
Pemetrexed is an effective treatment for advanced NSCLC, with an overall favorable toxicity profile. There is growing evidence that, in patients treated with pemetrexed, nonsquamous tumors have improved outcomes compared to squamous cell tumors. Pemetrexed may also have a role in maintenance therapy for NSCLC.
Fuld
Alexander D
AD
Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756, USA. Alexander.Fuld@Hitchcock.org
Dragnev
Konstantin H
KH
Rigas
James R
JR
D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D005971:Glutamates / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000068437:Pemetrexed; D015996:Survival Rate; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine