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The Role of Targeted Agents in the Treatment of Elderly Patients with Non-Small Cell Lung Cancer (NSCLC)

  • Lung Cancer
  • Published:
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Opinion statement

The introduction of targeted biological agents represents the most promising approach to improve the disease control and outcome for patients with non-small cell lung cancer. The epidermal growth factor and the vascular endothelial growth factor signaling pathways have been successfully targeted using both orally administered small molecule tyrosine kinase inhibitors and monoclonal antibodies, with associated improvement in overall survival. Although the trials that established the efficacy of these agents allowed the enrollment of patients older than 70 years, the elderly patients constituted the minority. Given the stringent enrolment criteria in terms of organ function and performance status for most clinical trials, the elderly patients on clinical trials are not entirely representative of the overall elderly patient population. Therefore, the applicability of these data to the overall patient population deserves critical appraisal in the absence of trials dedicated specifically to the elderly. Preplanned and unplanned subset analysis of registration trial data is becoming increasingly common as a substitute measure to provide valuable information to guide the use of targeted agents in the elderly. Using this approach, it has been demonstrated that elderly patients are able to tolerate targeted biological therapies but suffer increased rate of toxicities. However, they derive benefit from such agents when they are carefully selected and have their drug doses adjusted appropriately to minimize potential toxicities. This article reviews the use of targeted agents for the treatment of NSCLC in elderly patients.

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References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ: Cancer statistics, 2008. CA Cancer J Clin 2008, 58:71–96. doi:10.3322/CA.2007.0010

    Article  PubMed  Google Scholar 

  2. He W, Sengupta M, VelKoff VA: 65 + in the United States: 2005. Current Population Reports. Washington D.C.: U.S. Government Printing Office; 2005: 23–209

  3. Owonikoko TK, Ragin CC, Belani CP, Oton AB, Gooding WE, Taioli E, Ramalingam SS: Lung cancer in elderly patients: an analysis of the surveillance, epidemiology, and end results database. J Clin Oncol 2007, 25:5570–5577. doi:10.1200/JCO.2007.12.5435

    Article  PubMed  Google Scholar 

  4. GridelliC: The ELVIS trial: a phase III study of single-agent vinorelbine as first-line treatment in elderly patients with advanced non-small cell lung cancer. Elderly Lung Cancer Vinorelbine Italian Study. Oncologist 2001, 6(Suppl 1):4–7. doi:10.1634/theoncologist.6-suppl_1-4

  5. Shepherd FA, Rodrigues Pereira J, Ciuleanu T, Tan EH, Hirsh V, Thongprasert S, Campos D, Maoleekoonpiroj S, Smylie M, Martins R, et al.: Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005, 353:123–132. doi:10.1056/NEJMoa050753

    Article  PubMed  CAS  Google Scholar 

  6. Wheatley-Price P, Ding K, Seymour L, Clark GM, Shepherd FA. Erlotinib for advanced non-small-cell lung cancer in the elderly: an analysis of the National Cancer Institute of Canada Clinical Trials Group Study BR.21. J Clin Oncol 2008, 26:2350–2357. doi:10.1200/JCO.2007.15.2280

    Article  PubMed  CAS  Google Scholar 

  7. Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, Nishiwaki Y, Vansteenkiste J, Kudoh S, Rischin D, et al.: Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial) [corrected]. J Clin Oncol 2003, 21:2237–2246. doi:10.1200/JCO.2003.10.038

    Article  PubMed  CAS  Google Scholar 

  8. Kris MG, Natale RB, Herbst RS, Lynch TJ, Jr., Prager D, Belani CP, Schiller JH, Kelly K, Spiridonidis H, Sandler A, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial. JAMA 2003, 290:2149–2158. doi:10.1001/jama.290.16.2149

    Article  PubMed  CAS  Google Scholar 

  9. Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, Thongprasert S, Tan EH, Pemberton K, Archer V, et al.: Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer). Lancet 2005, 366:1527–1537. doi:10.1016/S0140-6736(05)67625-8

    Article  PubMed  CAS  Google Scholar 

  10. Gridelli C, Maione P, Castaldo V, Rossi A: Gefitinib in elderly and unfit patients affected by advanced non-small-cell lung cancer. Br J Cancer 2003, 89:1827–1829. doi:10.1038/sj.bjc.6601387

    Article  PubMed  CAS  Google Scholar 

  11. Hotta K, Ueoka H, Kiura K, Tabata M, Ogino A, Umemura S, Harita S, Gemba K, Yonei T, Bessho A, et al.: Safety and efficacy of gefitinib treatment in elderly patients with non-small-cell lung cancer: Okayama Lung Cancer Study Group experience. Acta Oncol 2005, 44:717–722. doi:10.1080/02841860500256215

    Article  PubMed  CAS  Google Scholar 

  12. Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, Zhu J, Johnson DH: Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002, 346:92–98. doi:10.1056/NEJMoa011954

    Article  PubMed  CAS  Google Scholar 

  13. Gridelli C, Aapro M, Ardizzoni A, Balducci L, De Marinis F, Kelly K, Le Chevalier T, Manegold C, Perrone F, Rosell R, et al.: Treatment of advanced non-small-cell lung cancer in the elderly: results of an international expert panel. J Clin Oncol 2005, 23:3125–3137. doi:10.1200/JCO.2005.00.224

    Article  PubMed  CAS  Google Scholar 

  14. Gridelli C, Perrone F, Gallo C, Cigolari S, Rossi A, Piantedosi F, Barbera S, Ferrau F, Piazza E, Rosetti F, et al.: Chemotherapy for elderly patients with advanced non-small-cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES) phase III randomized trial. J Natl Cancer Inst 2003, 95:362–372.

    Article  PubMed  CAS  Google Scholar 

  15. Langer CJ, Manola J, Bernardo P, Kugler JW, Bonomi P, Cella D, Johnson DH: Cisplatin-based therapy for elderly patients with advanced non-small-cell lung cancer: implications of Eastern Cooperative Oncology Group 5592, a randomized trial. J Natl Cancer Inst 2002, 94:173–181.

    PubMed  Google Scholar 

  16. Lilenbaum RC, Herndon JE, 2nd, List MA, Desch C, Watson DM, Miller AA, Graziano SL, Perry MC, Saville W, Chahinian P, et al.: Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730). J Clin Oncol 2005, 23:190–196. doi:10.1200/JCO.2005.07.172

    Article  PubMed  CAS  Google Scholar 

  17. Jackman DM, Yeap BY, Lindeman NI, Fidias P, Rabin MS, Temel J, Skarin AT, Meyerson M, Holmes AJ, Borras AM, et al.: Phase II clinical trial of chemotherapy-naive patients > or =70 years of age treated with erlotinib for advanced non-small-cell lung cancer. J Clin Oncol 2007, 25:760–766. doi:10.1200/JCO.2006.07.5754

    Article  PubMed  CAS  Google Scholar 

  18. Comella P, Frasci G, Carnicelli P, Massidda B, Buzzi F, Filippelli G, Maiorino L, Guida M, Panza N, Mancarella S, et al.: Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients. Br J Cancer 2004, 91:489–497. doi:10.1038/sj.bjc.6602011

    Article  PubMed  CAS  Google Scholar 

  19. Frasci G, Lorusso V, Panza N, Comella P, Nicolella G, Bianco A, De Cataldis G, Iannelli A, Bilancia D, Belli M, et al.: Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 2000, 18:2529–2536.

    PubMed  CAS  Google Scholar 

  20. Ramalingam S, Belani CP: State-of-the-art chemotherapy for advanced non-small cell lung cancer. Semin Oncol 2004, 31:68–74. doi:10.1053/j.seminoncol.2003.12.017

    Article  PubMed  CAS  Google Scholar 

  21. Lilenbaum R, Axelrod R, Thomas S, Dowlati A, Seigel L, Albert D, Witt K, Botkin D: Randomized phase II trial of erlotinib or standard chemotherapy in patients with advanced non-small-cell lung cancer and a performance status of 2. J Clin Oncol 2008, 26:863–869. doi:10.1200/JCO.2007.13.2720

    Article  PubMed  CAS  Google Scholar 

  22. Crinò L, Zatloukal P, Reck M, et al.: Gefitinib (IRESSA) versus vinorelbine in chemonaïve elderly patients with advanced non-small-cell lung cancer (INVITE): a randomized Phase II study: B3-04. J Thorac Oncol 2007, 2:S341. doi:10.1097/01.JTO.0000283157.88615.79

  23. Gatzemeier U, Hossfeld DK, Neuhauss R, Reck M, Achterrath W, Lenaz L: Phase II and III studies with carboplatin in small cell lung cancer. Semin Oncol 1992, 19:28–36.

    PubMed  CAS  Google Scholar 

  24. Giaccone G, Herbst RS, Manegold C, Scagliotti G, Rosell R, Miller V, Natale RB, Schiller JH, Von Pawel J, Pluzanska A, et al.: Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 1. J Clin Oncol 2004, 22:777–784. doi:10.1200/JCO.2004.08.001

    Article  PubMed  CAS  Google Scholar 

  25. Herbst RS, Giaccone G, Schiller JH, Natale RB, Miller V, Manegold C, Scagliotti G, Rosell R, Oliff I, Reeves JA, et al.: Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 2. J Clin Oncol 2004, 22:785–794. doi:10.1200/JCO.2004.07.215

    Article  PubMed  CAS  Google Scholar 

  26. Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, et al.: TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2005, 23:5892–5899. doi:10.1200/JCO.2005.02.840

    Article  PubMed  CAS  Google Scholar 

  27. Mendelsohn J, Baselga J: The EGF receptor family as targets for cancer therapy. Oncogene 2000, 19:6550–6565. doi:10.1038/sj.onc.1204082

    Article  PubMed  CAS  Google Scholar 

  28. Pirker R, Szczesna A, von Pawel J, et al.: 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 2008, 26:abstr 3

  29. Neuss MN, Desch CE, McNiff KK, Eisenberg PD, Gesme DH, Jacobson JO, Jahanzeb M, Padberg JJ, Rainey JM, Guo JJ, et al.: A process for measuring the quality of cancer care: the Quality Oncology Practice Initiative. J Clin Oncol 2005, 23:6233–6239. doi:10.1200/JCO.2005.05.948

    Article  PubMed  Google Scholar 

  30. Gridelli MC, Viganò F, Gebbia MG, et al.: Cetuximab (C) and gemcitabine (G) in elderly or adult PS2 advanced non small-cell lung cancer (NSCLC) patients (pts): The CALC1 randomised phase II trials. J Clin Oncol 2008, 26:abstract 8117

    Google Scholar 

  31. Sandler A, Gray R, Perry MC, Brahmer J, Schiller JH, Dowlati A, Lilenbaum R, Johnson DH: Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006, 355:2542–2550. doi:10.1056/NEJMoa061884

    Article  PubMed  CAS  Google Scholar 

  32. Ramalingam SS, Dahlberg SE, Langer CJ, Gray R, Belani CP, Brahmer JR, Sandler AB, Schiller JH, Johnson DH: Outcomes for elderly, advanced-stage non small-cell lung cancer patients treated with bevacizumab in combination with carboplatin and paclitaxel: analysis of Eastern Cooperative Oncology Group Trial 4599. J Clin Oncol 2008, 26:60–65. doi:10.1200/JCO.2007.13.1144

    Article  PubMed  CAS  Google Scholar 

  33. Langer CJ, Stephenson P, Thor A, Vangel M, Johnson DH: Trastuzumab in the treatment of advanced non-small-cell lung cancer: is there a role? Focus on Eastern Cooperative Oncology Group study 2598. J Clin Oncol 2004, 22:1180–1187. doi:10.1200/JCO.2004.04.105

    Article  PubMed  CAS  Google Scholar 

  34. Cabebe E, Wakelee H: Role of anti-angiogenesis agents in treating NSCLC: focus on bevacizumab and VEGFR tyrosine kinase inhibitors. Curr Treat Options Oncol 2007, 8:15–27. doi:10.1007/s11864-007-0022-4

    Article  PubMed  Google Scholar 

  35. Hanrahan EO, Heymach JV: Vascular endothelial growth factor receptor tyrosine kinase inhibitors vandetanib (ZD6474) and AZD2171 in lung cancer. Clin Cancer Res 2007, 13:s4617–4622. doi:10.1158/1078-0432.CCR-07-0539

    Article  PubMed  CAS  Google Scholar 

  36. Lynch TJ, Jr., Blumenschein GR, Jr., Engelman JA, Espinoza-Delgado I, Govindan R, Hanke J, Hanna NH, Heymach JV, Hirsch FR, Janne PA, et al.: Summary statement novel agents in the treatment of lung cancer: Fifth Cambridge Conference assessing opportunities for combination therapy. J Thorac Oncol 2008, 3:S107–112. doi:10.1097/JTO.0b013e3181630ece

    Article  PubMed  Google Scholar 

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  1. *Department of Hematology and Medical Oncology, Emory Winship Cancer Institute and Emory University School of Medicine, 1365 Clifton Road, Room # C-3090, Atlanta, GA , 30322, USA

    Taofeek K. Owonikoko MD, PhD & Suresh Ramalingam MD

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  1. Taofeek K. Owonikoko MD, PhD
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Correspondence to Suresh Ramalingam MD.

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Owonikoko, T.K., Ramalingam, S. The Role of Targeted Agents in the Treatment of Elderly Patients with Non-Small Cell Lung Cancer (NSCLC). Curr. Treat. Options in Oncol. 9, 313–325 (2008). https://doi.org/10.1007/s11864-008-0076-y

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