Expression of thymidylate synthase predicts clinical outcomes of pemetrexed-containing chemotherapy for non-small-cell lung cancer: a systemic review and meta-analysis.
OBJECTIVE
Observational and preclinical studies suggested an association between the expression of thymidylate synthase (TS) and clinical effects of pemetrexed-based chemotherapy in non-small-cell lung cancer (NSCLC) patients. However, the predictive value of TS for pemetrexed-containing chemotherapy regimen remained controversial. The aim of the study was to further appraise the association between the expression of TS and clinical efficacy pemetrexed-based chemotherapy in NSCLC patients.


METHODS
We searched in MEDLINE (PubMed), EMBASE, and Cochrane Library from January 1945 to May 2013. Two authors independently extracted information from the characteristics of study participants. Primary outcomes included therapeutic response (TR; i.e., complete response + partial response vs. stable disease + progressive disease), progression-free survival (PFS), and overall survival (OS). Relative risk (RR) and hazard ratio (HR) were used for evaluating the risk or hazard.


RESULTS
Eight studies were included in the meta-analysis. Better response usually appeared in NSCLC patients with a lower expression of TS [RR = 2.06 95 % confidence intervals (CI) 1.44, 2.96]. There was a significant association between TS expression and outcomes of pemetrexed-based chemotherapy for NSCLC (PFS: HR = 0.63 95 % CI 0.52, 0.76; OS: HR = 0.74, 95 % CI: 0.63, 0.88). In addition, no evidence of publication bias was observed.


CONCLUSIONS
This meta-analysis evaluated the predictive value of TS and provided evidence that NSCLC patients with lower TS expression could significantly benefit from pemetrexed-based chemotherapy. This increased level of TS was probably an independent risk factor of potential resistance against pemetrexed.
Department of Comprehensive Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095 Jie Fang Avenue, Wuhan, 430030, People's Republic of China.
Yu
Y
Liu
Tie-Jun
TJ
Yin
Rong
R
Zhou
Si
S
Zhou
Liang
L
Fan
Rong-Ge
RG
Zhang
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005971:Glutamates / Q000008:administration & dosage / Q000627:therapeutic use*; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D000068437:Pemetrexed; D011379:Prognosis; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D015415:Biomarkers; D005971:Glutamates; D009363:Neoplasm Proteins; D000068437:Pemetrexed; D006147:Guanine; D013940:Thymidylate Synthase