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Cancer Chemotherapy and Pharmacology

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01.11.2013 | Original Article

Expression of thymidylate synthase predicts clinical outcomes of pemetrexed-containing chemotherapy for non-small-cell lung cancer: a systemic review and meta-analysis

verfasst von: Yu Liu, Tie-Jun Yin, Rong Zhou, Si Zhou, Liang Fan, Rong-Ge Zhang

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 5/2013

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Abstract

Purpose

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.

Siegel R, Naishadham D, Jemal A (2013) Cancer statistics. CA Cancer J Clin 63(1):11–30. doi:10.3322/caac.21166 PubMedCrossRef

Wakelee H, Belani CP (2005) Optimizing first-line treatment options for patients with advanced NSCLC. Oncologist 10(Suppl 3):1–10. doi:10.1634/theoncologist.10-90003-1 PubMedCrossRef

Belani CP, Brodowicz T, Ciuleanu TE, Krzakowski M, Yang SH, Franke F, Cucevic B, Madhavan J, Santoro A, Ramlau R, Liepa AM, Visseren-Grul C, Peterson P, John WJ, Zielinski CC (2012) Quality of life in patients with advanced non-small-cell lung cancer given maintenance treatment with pemetrexed versus placebo (H3E-MC-JMEN): results from a randomised, double-blind, phase 3 study. Lancet Oncol 13(3):292–299. doi:10.1016/s1470-2045(11)70339-4 PubMedCrossRef

Belani CP, Wu YL, Chen YM, Kim JH, Yang SH, Zhang L, Peterson P, Orlando M (2012) Efficacy and safety of pemetrexed maintenance therapy versus best supportive care in patients from East Asia with advanced, nonsquamous non-small cell lung cancer: an exploratory subgroup analysis of a global, randomized, phase 3 clinical trial. J Thorac Oncol 7(3):567–573. doi:10.1097/JTO.0b013e31823d4f9d PubMedCrossRef

Gomez HL, Santillana SL, Vallejos CS, Velarde R, Sanchez J, Wang X, Bauer NL, Hockett RD, Chen VJ, Niyikiza C, Hanauske AR (2006) A phase II trial of pemetrexed in advanced breast cancer: clinical response and association with molecular target expression. Clinical Cancer Res Off J Am Assoc Cancer Res 12(3 Pt 1):832–838. doi:10.1158/1078-0432.CCR-05-0295 CrossRef

Popat S, Matakidou A, Houlston RS (2004) Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. J Clin Oncol 22(3):529–536. doi:10.1200/JCO.2004.05.064 PubMedCrossRef

Righi L, Papotti MG, Ceppi P, Billè A, Bacillo E, Molinaro L, Ruffini E, Scagliotti GV, Selvaggi G (2010) Thymidylate synthase but not excision repair cross-complementation group 1 tumor expression predicts outcome in patients with malignant pleural mesothelioma treated with pemetrexed-based chemotherapy. J Clin Oncol 28(9):1534–1539. doi:10.1200/JCO.2009.25.9275 PubMedCrossRef

Lustgarten DES, Deshpande C, Aggarwal C, Wang L-C, Saloura V, Vachani A, Wang L-P, Litzky L, Feldman M, Creaney J, Nowak AK, Langer C, Inghilleri S, Stella G, Albelda SM (2013) Thymidylate synthase and folyl-polyglutamate synthase are not clinically useful markers of response to pemetrexed in patients with malignant pleural mesothelioma. J Thorac Oncol 8(4):469–477. doi:10.1097/JTO.0b013e318283da3e PubMedCrossRef

Tanaka F, Wada H, Fukui Y, Fukushima M (2011) Thymidylate synthase (TS) gene expression in primary lung cancer patients: a large-scale study in Japanese population. Ann Oncol 22(8):1791–1797. doi:10.1093/annonc/mdq730 PubMedCrossRef

10.

Scagliotti GV, Ceppi P, Capelletto E, Novello S (2009) Updated clinical information on multitargeted antifolates in lung cancer. Clin Lung Cancer 10(Suppl 1):S35–S40. doi:10.3816/CLC.2009.s.006 PubMedCrossRef

11.

Rossi A, Galetta D, Gridelli C (2009) Biological prognostic and predictive factors in lung cancer. Oncology 77(Suppl 1):90–96. doi:10.1159/000258500 PubMedCrossRef

12.

Zheng Z, Li X, Schell MJ, Chen T, Boulware D, Robinson L, Sommers E, Bepler G (2008) Thymidylate synthase in situ protein expression and survival in stage I nonsmall-cell lung cancer. Cancer 112(12):2765–2773. doi:10.1002/cncr.23491 PubMedCrossRef

13.

Takezawa K, Okamoto I, Okamoto W, Takeda M, Sakai K, Tsukioka S, Kuwata K, Yamaguchi H, Nishio K, Nakagawa K (2011) Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancer. Br J Cancer 104(10):1594–1601PubMedCrossRef

14.

Chang MH, Ahn JS, Lee J, Kim KH, Park YH, Han J, Ahn MJ, Park K (2010) The efficacy of pemetrexed as a third- or fourth-line therapy and the significance of thymidylate synthase expression in patients with advanced non-small cell lung cancer. Lung Cancer 69(3):323–329PubMedCrossRef

15.

Bepler G, Sommers KE, Cantor A, Li X, Sharma A, Williams C, Chiappori A, Haura E, Antonia S, Tanvetyanon T, Simon G, Obasaju C, Robinson LA (2008) Clinical efficacy and predictive molecular markers of neoadjuvant gemcitabine and pemetrexed in resectable non-small cell lung cancer. J Thorac Oncol 3(10):1112–1118PubMedCrossRef

16.

Gadgeel SM, Ruckdeschel JC, Patel BB, Wozniak A, Konski A, Valdivieso M, Hackstock D, Chen W, Belzer K, Burger AM, Marquette L, Turrisi A (2011) Phase II study of pemetrexed and cisplatin, with chest radiotherapy followed by docetaxel in patients with stage III non-small cell lung cancer. J Thorac Oncol 6(5):927–933. doi:10.1097/JTO.0b013e3182156109 PubMedCrossRef

17.

Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR (2007) Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 8:16. doi:10.1186/1745-6215-8-16 PubMedCrossRef

18.

Higgins JPT, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. doi:10.1136/bmj.327.7414.557 PubMedCrossRef

19.

Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634PubMedCrossRef

20.

Wynes MW, Konopa K, Singh S, Reyna-Asuncion B, Ranger-Moore J, Sternau A, Christoph DC, Dziadziuszko R, Jassem J, Hirsch FR (2012) Thymidylate synthase protein expression by IHC and gene copy number by SISH correlate and show great variability in non-small cell lung cancer. J Thorac Oncol 7(6):982–992. doi:10.1097/JTO.0b013e31824fe95a PubMedCrossRef

21.

Hou J, Lambers M, den Hamer B, den Bakker MA, Hoogsteden HC, Grosveld F, Hegmans J, Aerts J, Philipsen S (2012) Expression profiling-based subtyping identifies novel non-small cell lung cancer subgroups and implicates putative resistance to pemetrexed therapy. J Thorac Oncol 7(1):105–114. doi:10.1097/JTO.0b013e3182352a45 PubMedCrossRef

22.

Tiseo M, Giovannetti E, Tibaldi C, Camerini A, Di Costanzo F, Barbieri F, Burgers JA, Vincent A, Peters GJ, Smit EF, Ardizzoni A (2012) Pharmacogenetic study of patients with advanced non-small cell lung cancer (NSCLC) treated with second-line pemetrexed or pemetrexed-carboplatin. Lung Cancer 78(1):92–99. doi:10.1016/j.lungcan.2012.07.009 PubMedCrossRef

23.

Smit EF, Socinski MA, Mullaney BP, Myrand SP, Scagliotti GV, Lorigan P, Reck M, Ciuleanu T, von Pawel J, Karaseva NA, Szczesna A, Ohannesian D, Powell E, Hozak RR, Hong S, Guba SC, Thatcher N (2012) Biomarker analysis in a phase III study of pemetrexed-carboplatin versus etoposide-carboplatin in chemonaive patients with extensive-stage small-cell lung cancer. Ann Oncol 23(7):1723–1729PubMedCrossRef

24.

Smit EF, Burgers SA, Biesma B, Smit HJM, Eppinga P, Dingemans A-MC, Joerger M, Schellens JH, Vincent A, van Zandwijk N, Groen HJM (2009) Randomized phase II and pharmacogenetic study of pemetrexed compared with pemetrexed plus carboplatin in pretreated patients with advanced non-small-cell lung cancer. J Clin Oncol 27(12):2038–2045. doi:10.1200/JCO.2008.19.1650 PubMedCrossRef

25.

Hu Q, Li X, Su C, Chen X, Gao G, Zhang J, Zhao Y, Li J, Zhou C (2012) Correlation between thymidylate synthase gene polymorphisms and efficacy of pemetrexed in advanced non-small cell lung cancer. Exp Ther Med 4(6):1010–1016PubMed

26.

Li WJ, Jiang H, Fang XJ, Ye HL, Liu MH, Liu YW, Chen Q, Zhang L, Zhang JY, Yuan CL, Zhang QY (2013) Polymorphisms in thymidylate synthase and reduced folate carrier (SLC19A1) genes predict survival outcome in advanced non-small cell lung cancer patients treated with pemetrexed-based chemotherapy. Oncol Lett 5(4):1165–1170PubMed

27.

Wang X, Wang Y, Wang Y, Cheng J, Wang Y, Ha M (2013) Association of thymidylate synthase gene 3′-untranslated region polymorphism with sensitivity of non-small cell lung cancer to pemetrexed treatment: TS gene polymorphism and pemetrexed sensitivity in NSCLC. J Biomed Sci 20(1)

28.

Shimizu T, Nakanishi Y, Nakagawa Y, Tsujino I, Takahashi N, Nemoto N, Hashimoto S (2012) Association between expression of thymidylate synthase, dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase and efficacy of pemetrexed in advanced non-small cell lung cancer. Anticancer Res 32(10):4589–4596PubMed

29.

Christoph DC, Asuncion BR, Hassan B, Tran C, Maltzman JD, O’Shannessy DJ, Wynes MW, Gauler TC, Wohlschlaeger J, Hoiczyk M, Schuler M, Eberhardt WE, Hirsch FR (2013) Significance of folate receptor alpha and thymidylate synthase protein expression in patients with non-small-cell lung cancer treated with pemetrexed. J Thorac Oncol 8(1):19–30PubMedCrossRef

30.

Igawa S, Ryuge S, Wada M, Otani S, Maki S, Takakura A, Katono K, Sasaki J, Sato Y, Masuda N (2012) Pemetrexed for previously treated patients with non-small cell lung cancer and differences in efficacy according to thymidylate synthase expression. Chemotherapy 58(4):313–320PubMedCrossRef

31.

Sun J-M, Han J, Ahn JS, Park K, Ahn M-J (2011) Significance of thymidylate synthase and thyroid transcription factor 1 expression in patients with nonsquamous non-small cell lung cancer treated with pemetrexed-based chemotherapy. J Thorac Oncol 6(8):1392–1399. doi:10.1097/JTO.0b013e3182208ea8 PubMedCrossRef

32.

Chen C-Y, Chang Y-L, Shih J-Y, Lin J-W, Chen K-Y, Yang C-H, Yu C-J, Yang P-C (2011) Thymidylate synthase and dihydrofolate reductase expression in non-small cell lung carcinoma: the association with treatment efficacy of pemetrexed. Lung Cancer 74(1):132–138. doi:10.1016/j.lungcan.2011.01.024 PubMedCrossRef

33.

Lee SH, Noh KB, Lee JS, Lee EJ, Min KH, Hur GY, Lee SH, Lee SY, Kim JH, Lee SY, Shin C, Shim JJ, Kim CH, Kang KH, In KH (2013) Thymidylate synthase and ERCC1 as predictive markers in patients with pulmonary adenocarcinoma treated with pemetrexed and cisplatin. Lung Cancer 81(1):102–108. doi:10.1016/j.lungcan.2013.03.002 PubMedCrossRef

34.

Mok TS, Wu Y-L, Thongprasert S, Yang C-H, Chu D-T, Saijo N, Sunpaweravong P, Han B, Margono B, Ichinose Y, Nishiwaki Y, Ohe Y, Yang J–J, Chewaskulyong B, Jiang H, Duffield EL, Watkins CL, Armour AA, Fukuoka M (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361(10):947–957. doi:10.1056/NEJMoa0810699 PubMedCrossRef

35.

Hubner RA, Riley RD, Billingham LJ, Popat S (2011) Excision repair cross-complementation group 1 (ERCC1) status and lung cancer outcomes: a meta-analysis of published studies and recommendations. PLoS ONE 6(10):e25164. doi:10.1371/journal.pone.0025164 PubMedCrossRef

36.

Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, Sharma A, Simon G (2006) RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol Off J Am Soc Clin Oncol 24(29):4731–4737. doi:10.1200/JCO.2006.06.1101 CrossRef

37.

Moreira LR, Schenka AA, Latuff Filho P, Nascimento H, Passos Lima CS, Silva Trevisan MA, Vassallo J (2009) Correlation between thymidylate synthase protein expression and gene polymorphism with clinicopathological parameters in colorectal carcinoma. Int J Surg Pathol 17(3):181–186. doi:10.1177/1066896908330480 PubMedCrossRef

38.

Laporte S, Squifflet P, Baroux N, Fossella F, Georgoulias V, Pujol J-L, Douillard J-Y, Kudoh S, Pignon J-P, Quinaux E, Buyse M (2013) Prediction of survival benefits from progression-free survival benefits in advanced non-small-cell lung cancer: evidence from a meta-analysis of 2334 patients from 5 randomised trials. BMJ Open 3(3). doi:10.1136/bmjopen-2012-001802

39.

Biesecker LG, Spinner NB (2013) A genomic view of mosaicism and human disease. Nat Rev Genet 14(5):307–320. doi:10.1038/nrg3424 PubMedCrossRef

Titel: Expression of thymidylate synthase predicts clinical outcomes of pemetrexed-containing chemotherapy for non-small-cell lung cancer: a systemic review and meta-analysis
verfasst von: Yu Liu
Tie-Jun Yin
Rong Zhou
Si Zhou
Liang Fan
Rong-Ge Zhang
Publikationsdatum: 01.11.2013
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 5/2013
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-013-2299-2

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Expression of thymidylate synthase predicts clinical outcomes of pemetrexed-containing chemotherapy for non-small-cell lung cancer: a systemic review and meta-analysis

Abstract

Purpose

Methods

Results

Conclusions

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Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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