The relationship between response to previous systemic treatment and the efficacy of subsequent pemetrexed therapy in advanced non-small cell lung cancer.
BACKGROUND
We sought to identify the relationship between response to previous systemic treatment and the efficacy of subsequent pemetrexed therapy in advanced non-small cell lung cancer (NSCLC).


METHODS
Two hundred and fifty clinical stage IIIB or IV NSCLC patients treated with pemetrexed as a second-line or further-line treatment between April 2007 and June 2008 were analyzed retrospectively. Prior therapies were divided into four types (gemcitabine-based [G], paclitaxel-based [P], docetaxel-based [D], and EGFR tyrosine kinase inhibitor [I]). Objective response rates (ORR) and progression-free survivals (PFS) for pemetrexed therapy were analyzed according to the response outcome with each previous treatment.


RESULTS
The ORR of pemetrexed therapy was higher for patients who had achieved partial response with previous [G] therapy than others (15.0% vs. 4.3%, p=0.02). In addition, median PFS for pemetrexed therapy was greater for responders to [G] than for nonresponders (3.0 months vs. 1.7 months, p=0.004). The longer PFS for responders to [G] was also shown in the analysis among patients with squamous cell carcinoma (3.2 months vs. 1.7 months, p=0.056). By univariate analyses, the variables of the responder to [G] therapy, female, adenocarcinoma, never smoking status, and ECOG performance status of 0-1 were good predictive factors for pemetrexed therapy in terms of PFS. Multivariate analysis revealed that only response to [G] had statistical significance (hazard ratio=0.62, p=0.006).


CONCLUSIONS
Response outcome to prior [G] therapy might predict the efficacy of subsequent pemetrexed therapy in advanced NSCLC.
Sun
Jong-Mu
JM
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Oh
Do-Youn
DY
Lee
Se-Hoon
SH
Kim
Dong-Wan
DW
Im
Seock-Ah
SA
Kim
Tae-You
TY
Lee
Jong Seok
JS
Kim
Young-Whan
YW
Heo
Dae Seog
DS
Bang
Yung-Jue
YJ
D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018450:Disease Progression; D000077143:Docetaxel; D004359:Drug Therapy, Combination; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D000069347:Erlotinib Hydrochloride; D005260:Female; D005971:Glutamates / Q000008:administration & dosage* / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D000068437:Pemetrexed; D011379:Prognosis; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D012189:Retrospective Studies; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
D005971:Glutamates; D011799:Quinazolines; D043823:Taxoids; D000068437:Pemetrexed; D003841:Deoxycytidine; D000077143:Docetaxel; D006147:Guanine; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D017239:Paclitaxel; D000093542:Gemcitabine