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Individualizing Chemotherapy for Non-small Cell Lung Cancer (NSCLC) in the Adjuvant and Advanced Setting: Current Status and Future Directions

  • Lung Cancer
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Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Treatments based on molecular determinants are likely to be increasingly explored in the future. Future challenges will include ensuring that molecular determinants are identified as novel chemotherapeutic agents are being developed, enabling rationale therapeutics. Clinical trials will then enrich patients with the molecular determinants, potentially increasing response rates and survival in a specific group of patients who express this molecular determinant. It is hoped that this patient-specific ‹individualized cocktails’ will substantially improve response rates and survival.

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References and Recommended Readings

  1. 1. Bepler G, Begum M, Simon GR. Molecular analysis-based treatment strategies for non-small cell lung cancer. Cancer Control 2008; 15: 130–9.

    PubMed  Google Scholar 

  2. 2. Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005; 352: 2589–97. doi:10.1056/NEJMoa043623

    Article  PubMed  CAS  Google Scholar 

  3. 3. Arriagada R, Bergman B, Dunant A, Le Chevalier T, Pignon JP, Vansteenkiste J. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004; 350: 351–60. doi:10.1056/NEJMoa031644

    Article  PubMed  Google Scholar 

  4. 4. Pignon JP, Tribodet H, Scagliotti GV, et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol 2008; 26: 3552–9. doi:10.1200/JCO.2007.13.9030

    Article  PubMed  Google Scholar 

  5. 5. Brock MV, Hooker CM, Ota-Machida E, et al. DNA methylation markers and early recurrence in stage I lung cancer. N Engl J Med 2008; 358: 1118–28. doi:10.1056/NEJMoa0706550

    Article  PubMed  CAS  Google Scholar 

  6. 6. Hoeijmakers JH. Nucleotide excision repair I: from E. coli to yeast. Trends Genet 1993; 9: 173–7. doi:10.1016/0168-9525(93)90164-D

    Article  PubMed  CAS  Google Scholar 

  7. 7. Simon GR, Begum M, Bepler G. Setting the stage for tailored chemotherapy in the management of non-small cell lung cancer. Future Oncol 2008; 4: 51–9. doi:10.2217/14796694.4.1.51

    Article  PubMed  CAS  Google Scholar 

  8. 8. Simon GR, Sharma S, Cantor A, Smith P, Bepler G. ERCC1 expression is a predictor of survival in resected patients with non-small cell lung cancer. Chest 2005; 127: 978–83. doi:10.1378/chest.127.3.978

    Article  PubMed  Google Scholar 

  9. 9. Olaussen KA, Dunant A, Fouret P, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 2006; 355: 983–91. doi:10.1056/NEJMoa060570

    Article  PubMed  CAS  Google Scholar 

  10. 10. Filipits M, Pirker R, Dunant A, et al. Cell cycle regulators and outcome of adjuvant cisplatin-based chemotherapy in completely resected non-small-cell lung cancer: the International Adjuvant Lung Cancer Trial Biologic Program. J Clin Oncol 2007; 25: 2735–40. doi:10.1200/JCO.2006.08.2867

    Article  PubMed  CAS  Google Scholar 

  11. 11. Esposito V, Baldi A, De Luca A, et al. Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer. Cancer Res 1997; 57: 3381–5.

    PubMed  CAS  Google Scholar 

  12. 12. Elledge SJ, Zhou Z, Allen JB. Ribonucleotide reductase: regulation, regulation, regulation. Trends Biochem Sci 1992; 17: 119–23. doi:10.1016/0968-0004(92)90249-9

    Article  PubMed  CAS  Google Scholar 

  13. 13. Gautam A, Bepler G. Suppression of lung tumor formation by the regulatory subunit of ribonucleotide reductase. Cancer Res 2006; 66: 6497–502. doi:10.1158/0008-5472.CAN-05-4462

    Article  PubMed  CAS  Google Scholar 

  14. 14. Bepler G, Gautam A, McIntyre LM, et al. 2002 Prognostic significance of molecular genetic aberrations on chromosome segment 11p15.5 in non-small-cell lung cancer. J Clin Oncol 20: 1353–60. doi:10.1200/JCO.20.5.1353

    Article  PubMed  CAS  Google Scholar 

  15. 15. Bepler G, Kusmartseva I, Sharma S, et al. RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol 2006; 24: 4731–7. doi:10.1200/JCO.2006.06.1101

    Article  PubMed  CAS  Google Scholar 

  16. 16. Zheng Z, Chen T, Li X, Haura E, Sharma A, Bepler G. DNA synthesis and repair genes RRM1 and ERCC1 in lung cancer. N Engl J Med 2007; 356: 800–8. doi:10.1056/NEJMoa065411

    Article  PubMed  CAS  Google Scholar 

  17. 17. Wachters FM, Wong LS, Timens W, Kampinga HH, Groen HJ. ERCC1, hRad51, and BRCA1 protein expression in relation to tumour response and survival of stage III/IV NSCLC patients treated with chemotherapy. Lung Cancer 2005; 50: 211–9. doi:10.1016/j.lungcan.2005.06.013

    Article  PubMed  CAS  Google Scholar 

  18. 18. Rosell R, Skrzypski M, Jassem E, et al. 2007 BRCA1: a novel prognostic factor in resected non-small-cell lung cancer. PLoS ONE 2: e1129. doi:10.1371/journal.pone.0001129

    Article  PubMed  Google Scholar 

  19. 19. Wang L, Wei J, Qian X, et al. 2008 ERCC1 and BRCA1 mRNA expression levels in metastatic malignant effusions is associated with chemosensitivity to cisplatin and/or docetaxel. BMC Cancer 8: 97. doi:10.1186/1471-2407-8-97

    Article  PubMed  Google Scholar 

  20. Cobo M, Massuti B, Moran T, et al. (2008) Spanish customized adjuvant trial (SCAT) based on BRCA1 mRNA levels. J Clin Oncol 26: S20. doi:10.1200/JCO.2007.11.6905

    Article  Google Scholar 

  21. 21. Gan PP, Pasquier E, Kavallaris M. Class III beta-tubulin mediates sensitivity to chemotherapeutic drugs in non small cell lung cancer. Cancer Res 2007; 67: 9356–63. doi:10.1158/0008-5472.CAN-07-0509

    Article  PubMed  CAS  Google Scholar 

  22. 22. Seve P, Lai R, Ding K, et al. 2007 Class III beta-tubulin expression and benefit from adjuvant cisplatin/vinorelbine chemotherapy in operable non-small cell lung cancer: analysis of NCIC JBR.10. Clin Cancer Res 13: 994–9. doi:10.1158/1078-0432.CCR-06-1503

    Article  PubMed  CAS  Google Scholar 

  23. 23. Potti A, Mukherjee S, Petersen R, et al. A genomic strategy to refine prognosis in early-stage non-small-cell lung cancer. N Engl J Med 2006; 355: 570–80. doi:10.1056/NEJMoa060467

    Article  PubMed  CAS  Google Scholar 

  24. 24. Chen HY, Yu SL, Chen CH, et al. A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 2007; 356: 11–20. doi:10.1056/NEJMoa060096

    Article  PubMed  CAS  Google Scholar 

  25. 25. Amann JM, Chaurand P, Gonzalez A, et al. Selective profiling of proteins in lung cancer cells from fine-needle aspirates by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Clin Cancer Res 2006; 12: 5142–50. doi:10.1158/1078-0432.CCR-06-0264

    Article  PubMed  CAS  Google Scholar 

  26. 26. Yanagisawa K, Shyr Y, Xu BJ, et al. Proteomic patterns of tumour subsets in non-small-cell lung cancer. Lancet 2003; 362: 433–9. doi:10.1016/S0140-6736(03)14068-8

    Article  PubMed  CAS  Google Scholar 

  27. 27. Schiller JH, Harrinton D, Sandler A, et al. 2000 A randomized phase III trial of four chemotherapy regimens in advanced Non-Small Cell Lung cancer(NSCLC). Proceedings of ASCO 19: 1a.

    Google Scholar 

  28. 28. Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542–50. doi:10.1056/NEJMoa061884

    Article  PubMed  CAS  Google Scholar 

  29. Pirker R, Szczesna A, von Pawel J, et al. (2008) FLEX: A randomized, multicenter, phase III study of cetuximab in combination with cisplatin/vinorelbine (CV) versus CV alone in the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC). J Clin Oncol 26: 1006s.

    Article  Google Scholar 

  30. 30. Lord RV, Brabender J, Gandara D, et al. Low ERCC1 Expression Correlates with Prolonged Survival after Cisplatin plus Gemcitabine Chemotherapy in Non-Small Cell Lung Cancer. Clin Cancer Res 2002; 8: 2286–91.

    PubMed  CAS  Google Scholar 

  31. Simon GR, Sharma A, Li X, et al.: Feasibility and efficacy of molecular analysis-directed individualized therapy in advanced non-small-cell lung cancer. J Clin Oncol 2007, (in press)

  32. 32. Cobo M, Isla D, Massuti B, et al. Customizing cisplatin based on quantitative excision repair cross-complementing 1 mRNA expression: a phase III trial in non-small-cell lung cancer. J Clin Oncol 2007; 25: 2747–54. doi:10.1200/JCO.2006.09.7915

    Article  PubMed  CAS  Google Scholar 

  33. 33. Ceppi P, Volante M, Saviozzi S, et al. Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase. Cancer 2006; 107: 1589–96. doi:10.1002/cncr.22208

    Article  PubMed  CAS  Google Scholar 

  34. 34. Hanauske AR, Eismann U, Oberschmidt O, et al. In vitro chemosensitivity of freshly explanted tumor cells to pemetrexed is correlated with target gene expression. Invest New Drugs 2007; 25: 417–23. doi:10.1007/s10637-007-9060-9

    Article  PubMed  CAS  Google Scholar 

  35. 35. Hanna N, Shepherd FA, Fossella FV, et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004; 22: 1589–97. doi:10.1200/JCO.2004.08.163

    Article  PubMed  CAS  Google Scholar 

  36. Peterson P, Park K, Fossella F, et al. (2007) Is pemetrexed more effective in patients with non-squamous histology? A retrospective analysis of a phase III trial of pemetrexed vs docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC). Eur J Cancer 5: S4.

    Google Scholar 

  37. 37. Scagliotti GV, Parikh P, von Pawel J, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008; 26: 3543–51. doi:10.1200/JCO.2007.15.0375

    Article  PubMed  CAS  Google Scholar 

  38. 38. Potti A, Dressman HK, Bild A, et al. Genomic signatures to guide the use of chemotherapeutics. Nat Med 2006; 12: 1294–300. doi:10.1038/nm1491

    Article  PubMed  CAS  Google Scholar 

  39. 39. Simon G, Sharma A, Li X, et al. Feasibility and efficacy of molecular analysis-directed individualized therapy in advanced non-small-cell lung cancer. J Clin Oncol 2007; 25: 2741–6. doi:10.1200/JCO.2006.08.2099

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Thoracic Oncology Program for Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA

    George R. Simon MD, FACP, FCCP

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  1. George R. Simon MD, FACP, FCCP
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Correspondence to George R. Simon MD, FACP, FCCP.

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Simon, G.R. Individualizing Chemotherapy for Non-small Cell Lung Cancer (NSCLC) in the Adjuvant and Advanced Setting: Current Status and Future Directions. Curr. Treat. Options in Oncol. 9, 300–312 (2008). https://doi.org/10.1007/s11864-008-0075-z

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  • DOI: https://doi.org/10.1007/s11864-008-0075-z

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