A review of the management of elderly patients with non-small-cell lung cancer

Annals of Oncology

Volumn 26, Issue 3, 2015, Pages 451-463

  Blanco, R ^a   Maestu, Inmaculada ^b   de la Torre, M G ^c   Cassinello, A ^c   Nunez I ^c  

^a Terrassa   (Spain)

^b HOSPITAL UNIVERSITARIO DR PESET   (Spain)

^c Medical Department   (Spain)

Author keywords

Elderly; Management; Non small cell lung cancer

Indexed keywords

BEVACIZUMAB; CARBOPLATIN; CISPLATIN; DOCETAXEL; EPIDERMAL GROWTH FACTOR RECEPTOR KINASE INHIBITOR; ERLOTINIB; ETOPOSIDE; GEFITINIB; GEMCITABINE; NAVELBINE; PACLITAXEL; PEMETREXED;

ADVANCED CANCER; AGED; CANCER ADJUVANT THERAPY; CANCER PALLIATIVE THERAPY; CANCER PROGNOSIS; CANCER STAGING; CANCER SURVIVAL; CHEMORADIOTHERAPY; CLINICAL TRIAL (TOPIC); DAILY LIFE ACTIVITY; DRUG CHOICE; DRUG EFFICACY; DRUG FATALITY; DRUG SAFETY; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; ELDERLY CARE; EVIDENCE BASED MEDICINE; EXPECTATION; FEASIBILITY STUDY; FRAIL ELDERLY; GERIATRIC ASSESSMENT; HIGH RISK POPULATION; HUMAN; INFECTION; INOPERABLE CANCER; LIFE EXPECTANCY; LOW DRUG DOSE; LUNG LOBECTOMY; MEDICAL DECISION MAKING; META ANALYSIS (TOPIC); NEUTROPENIA; NON SMALL CELL LUNG CANCER; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PATIENT ATTITUDE; PATIENT PARTICIPATION; PATIENT SELECTION; PHASE 3 CLINICAL TRIAL (TOPIC); PHYSICIAN ATTITUDE; POLYPHARMACY; POSTOPERATIVE CARE; PRACTICE GUIDELINE; PREOPERATIVE EVALUATION; PRIORITY JOURNAL; RADIOFREQUENCY ABLATION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK BENEFIT ANALYSIS; STEREOTACTIC BODY RADIATION THERAPY; STUDY DESIGN; SURGICAL APPROACH; SURGICAL RISK; SURVIVAL TIME; SYSTEMATIC REVIEW (TOPIC); TREATMENT INDICATION; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; ADJUVANT CHEMOTHERAPY; ADJUVANT RADIOTHERAPY; CARCINOMA, NON-SMALL-CELL LUNG; DISEASE MANAGEMENT; LUNG NEOPLASMS; MULTIMODALITY CANCER THERAPY; PROCEDURES; VERY ELDERLY;

AGED; AGED, 80 AND OVER; CARCINOMA, NON-SMALL-CELL LUNG; CHEMOTHERAPY, ADJUVANT; CLINICAL TRIALS AS TOPIC; COMBINED MODALITY THERAPY; DISEASE MANAGEMENT; GERIATRIC ASSESSMENT; HUMANS; LUNG NEOPLASMS; RADIOTHERAPY, ADJUVANT;

EID: 84937032908     PISSN: 09237534     EISSN: 15698041     Source Type: Journal    
DOI: 10.1093/annonc/mdu268     Document Type: Review

References (165)

1. Quaglia A, Tavilla A, Shack L et al. The cancer survival gap between elderly and middle aged patients in Europe is widening. Eur J Cancer 2009; 45: 1006-1016.
2. OECD (2010), Health at a Glance: Europe 2010, OECD Publishing.
3. Vora N, Reckamp KL. Non-small cell lung cancer in the elderly: defining treatment options. Sem Oncol 2008; 6: 590-596.
4. Piccirillo JF, Tierney RM, Costas I, Grove L, Spitznagel EL Jr. Prognostic importance of comorbidity in a hospital-based cancer registry. JAMA 2004; 291: 2441-2447.
5. Jørgensen TL, Hallas J, Land LH, Herrstedt J. Comorbidity and polypharmacy in elderly patients. The significance on treatment outcome and tolerance. J Geriat Oncol 2010; 1: 87-102.
6. Lees J, Chan A. Polypharmacy in elderly patients with cancer: clinical implications and management. Lancet Oncol 2011; 12: 1249-1257.
7. Young A. Ageing and physiological functions. Phil Trans R Soc Lond 1997; 352: 1837-1843.
8. Balducci L. Aging, frailty and chemotherapy. Cancer Control 2007; 14: 7-12.
9. Balducci L. ESH-SIOG International Conference on Haematological Malignancies in the Elderly. Expert Rev Hematol 2010; 3: 675-677.
10. Albain KS, Crowley JJ, LeBlanc M, Livingston RB. Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience. J Clin Oncol 1991; 9: 1618-1626.
11. Repetto L, Fratino L, Audisio RA et al. Comprehensive geriatric assessment adds information to Eastern Cooperative Oncology Group performance status in elderly cancer patients: an Italian Group for Geriatric Oncology Study. J Clin Oncol 2002; 20: 494-502.
12. Maione P, Perrone F, Gallo C et al. Pretreatment quality of life and functional status assessment significantly predict survival of elderly patients with advanced non-small-cell lung cancer receiving chemotherapy: a prognostic analysis of the multicenter Italian lung cancer in the elderly study. J Clin Oncol 2005; 23: 6865-6872.
13. Maestu I, Muñoz J, Gómez-Aldaraví L et al. Assessment of functional status, symptoms and comorbidity in elderly patients with advanced non-small-cell lung cancer (NSCLC) treated with gemcitabine and vinorelbine. Clin Trans Oncol 2007; 9: 99-105.
14. Blanc-Bisson C, Fonck M, Rainfray M, Soubeyran P, Bourdel-Marchasson I. Undernutrition in elderly patients with cancer: target for diagnosis and intervention. Crit Rev Oncol Hematol 2008; 67: 243-254.
15. Arrieta O, Michel Ortega RM, Villanueva-Rodriguex G et al. Association of nutritional status and serum albumin levels with development of toxicity in patients with advanced non-small cell lung cancer treated with paclitaxelcisplatin chemotherapy: a prospective study. BMC Cancer 2010; 10: 50.
16. British Geriatrics Society. Comprehensive Assessment of the Frail Older Patient; http://www.bgs.org.uk/index.php/topresources/publicationfind/goodpractice/195-gpgcgassessment (26 November 2013, date last accessed).
17. Extermann M, Hurria A. Comprehensive Geriatric Assessment for older patients with cancer. J Clin Oncol 2007; 14: 1824-1831.
18. Mohile SG, Klepin HD, Rao AV. Considerations and controversies in the management of older patients with advanced cancer. Am Soc Clin Oncol Educ Book 2012; 321-328.
19. Wildiers H, Kenis C. Comprehensive geriatric assessment (CGA) in older oncological patients: why and how. J Geriatr Oncol 2012; 3: 174-176.
20. Extermann M. Integrating a geriatric evaluation in the clinical setting. Semin Radiat Oncol 2012; 22: 272-276.
21. Wedding U, Kösdding D, Pientka L, Steinmetz HT, Schmitz S. Physicians' judgement and comprehensive geriatric assessment (CGA) select different patients as fit for chemotherapy. Crit Rev Oncol Hematol 2007; 64: 1-9.
22. Hurria A, Togawa K, Mohile SG et al. Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol 2011; 29: 3457-3465.
23. Puts MT, Hardt J, Monette J et al. Use of Geriatric Assessment for older adults in the oncology setting: a systematic review. J Natl Cancer Inst 2012; 104: 1133-1163.
24. Overcash JA, Beckstead J, Extermann M, Cobb S. The abbreviated comprehensive geriatric assessment (aCGA): a retrospective analysis. Crit Rev Oncol Hematol 2005; 54: 129-136.
25. Overcash JA, Beckstead J, Moody L, Extermann M, Cobb S. The abbreviated comprehensive geriatric assessment (aCGA) for use in the older cancer patient as a prescreen: scoring and interpretation. Crit Rev Oncol Hematol 2006; 59: 205-210.
26. Hamaker ME, Jonker JM, de Rooij SE et al. Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients: a systematic review. Lancet Oncol 2012; 13: e437-e444.
27. Barber JH, Wallis JB, McKeating E. A postal screening questionnaire in preventive geriatric care. J R Coll Gen Pract 1980; 30: 49-51.
28. Fairhall N, Aggar C, Kurrie SE et al. Frailty Intervention Trial (FIT). BMC Geriatr 2008; 8: 27.
29. Bellera C, Rainfray M, Mathoulin-Plissier S, Soubeyran I. Validation of a screening tool in geriatric oncology: the ONCODAGE project. Crit Rev Oncol Hematol 2008; 68: S22.
30. Schuurmans H, Steverink N, Lindenberg S, Frieswijk N, Slaets JP. Old or frail: what tells us more? J Gerontol A Biol Sci Med Sci 2004; 59: M962-M965.
31. Valero S, Migeot V, Bouche G et al. Who needs a comprehensive geriatric assessment? A French Onco-Geriatric Screening Tool (OGS). J Geriatr Oncol 2011; 2: 130-136.
32. Extermann M, Green T, Tiffenberg G, Rich CJ. Validation of the Senior Adult Oncology Program (SAOP) 2 screening questionnaire. Crit Rev Oncol Hematol 2009; 69: 185.
33. Mion LC, Palmer RM, Anetzberger GJ, Meldon SW. Establishing a case-finding and referral system for at-risk older individuals in the emergency department setting: the SIGNET model. J Am Geriatr Soc 2001; 49: 1379-1386.
34. Saliba S, Elliot M, Rubenstein LA et al. The vulnerable elders survey (VES-13): a tool for identifying vulnerable elders in the community. J Am Geriatr Soc 2001; 49: 1691-1699.
35. Gironés R, Torregrosa D, Gomez-Codina J et al. Lung cancer chemotherapy decisions in older patients: the role of patient preference and interactions with physicians. Clin Trans Oncol 2012; 14: 183-189.
36. Sterlacci W, Stockinger R, Schmid T et al. The elderly patient with surgically resected non-small cell lung cancer-a distinct situation. Exp Gerontol 2012; 47: 237-242.
37. Bridges JFP, Mohamed AE, Finnern HW, Woehl A, Hauber AB. Patients' preferences for treatment outcomes for advanced non-small cell lung cancer: a conjoint analysis. Lung Cancer 2012; 77: 224-231.
38. Pallis AG, Gridelli C, van Meerbeeck JP et al. EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology (SIOG) experts' opinion for the treatment of non-small cell lung cancer in an elderly population. Ann Oncol 2010; 21: 692-706.
39. Rivera C, Falcoz PE, Bernard A, Thomas PA, Dahan M. Surgical management and outcomes of elderly patients with early stage non-small cell lung cancer. Chest 2011; 140: 874-880.
40. Gray SW, Landrum MB, Lamont EB et al. Improved outcomes associated with higher surgery rates for older patients with early stage nonsmall cell lung cancer. Cancer 2012; 118: 1404-1411.
41. Chambers A, Routledge T, Pilling J, Scarci M. In elderly patients with lung cancer is resection justified in terms of morbidity, mortality and quality of life? Interact Cardiovasc Thorac Surg 2010; 10: 1015-1021.
42. Yamamoto K, Padilla-Alarcon J, Calvo-Medina V et al. Surgical results of stage I non-small cell lung cancer: comparison between elderly and younger patients. Eur J Cardiothorac Surg 2003; 23: 21-25.
43. Kates M, Perez X, Gribetz J et al. Validation of a model to predict perioperative mortality from lung cancer resection in the elderly. Am J Respir Crit Care Med 2009; 179: 390-395.
44. Preoperative Assessment of Cancer in the Elderly. Shall we operate? Preoperative assessment in elderly cancer patients (PACE) can help. A SIOG surgical task force prospective study. Crit Rev Oncol Hematol 2008; 65: 156-163.
45. Mendoza TR, Wang XS, Cleeland CS et al. The rapid assessment of fatigue severity in cancer patients: use of the brief fatigue inventory. Cancer 1999; 85: 1186-1196.
46. Shiono S, Abiko M, Sato T. Postoperative complications in elderly patients after lung cancer surgery. Interact Cardiovasc Thorac Surg 2013; 16: 819-823.
47. Heerdt PM, Park BJ. The emerging role of minimally invasive surgical techniques for the treatment of lung malignancy in the elderly. Anaesthesiol Clin 2008; 26: 315-324.
48. Mery CM, Pappas AN, Bueno R et al. Similar long-term survival of elderly patients with non-small cell lung cancer treated with lobectomy or wedge resection within the surveillance, epidemiology and end-results database. Chest 2005; 128: 237-245.
49. Okami J, Ito Y, Higashiyama M et al. Sublobar resection provides an equivalent survival after lobectomy in patients elderly patients with early lung cancer. Ann Thorac Surg 2010; 90: 1651-1657.
50. Thomas P, Sielezneff I, Ragni J, Giudicelli R, Fuentes P. Is lung cancer resection justified in patients aged over 70 years? Eur J Cardiothorac Surg 1993; 7: 246-251.
51. Spaggiari L, Scanagatta P. Surgery of non-small cell lung cancer in the elderly. Curr Opin Oncol 2007; 19: 84-91.
52. Pallis AG, Scarci M. Are we treating enough elderly patients with early stage nonsmall cell lung cancer? Lung Cancer 2010; 74: 149-154.
53. Karl RC, Smith SK, Fabri PJ. Validity of major cancer operations in elderly patients. Ann Surg Oncol 1995; 2: 107-113.
54. Rowell NP, Williams CJ. Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable). Cochrane Database System Rev 2001; 2: CD002935.
55. Wisnivesky JP, Halm E, Bonomi M, Powell C, Bagiella E. Effectiveness of radiation therapy for elderly patients with unresected stage I and II non-small cell lung cancer. Am J Resp Crit Care Med 2010; 181: 264-269.
56. Palma DA, Tyldesley S, Sheehan F et al. Stage I non-small cell lung cancer (NSCLC) in patients aged 75 years and over: does age determine survival after radical treatment. J Thorac Oncol 2010; 5: 818-824.
57. Bayman N, Alam N, Faivre-Finn C. Radiotherapy for lung cancer in the elderly. Lung Cancer 2010; 68: 129-136.
58. Rodrigues G, Sanatani M. Age and co-morbidity considerations related to radiotherapy and chemotherapy administration. Semin Radiat Oncol 2012; 22: 277-283.
59. National Comprehensive Cancer Network. NCCN Guidelines: non-Small Cell Lung Cancer, v2. 2013; http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf (24 January 2013, date last accessed).
60. Verbakel WF, Senan S, Cuijpers JP, Slotman BJ, Lagerwaard FJ. Rapid delivery of stereotactic radiotherapy for peripheral lung tumors using volumetric intensitymodulated arcs. Radiother Oncol 2009; 93: 122-124.
61. Ebright MI, Fernando HC. Surgical resection or stereotactic body radiation therapy in elderly patients with early stage lung cancer: evolving treatment algorithms and a call for reliable comparisons. Semin Thorac Surg 2011; 23: 93-95.
62. Louie AV, Rodrigues G, Hannouf M et al. Stereotactic body radiotherapy versus surgery for medically operable stage I non-small-cell lung cancer: a Markov model-based decision analysis. Int J Radiat Oncol Biol Phys 2011; 81: 964-973.
63. Senan S, Palma D, Lagerwaard FJ. Stereotactic ablative radiotherapy for stage I NSCLC: recent advances and controversies. J Thorac Dis 2011; 3: 189-196.
64. de Baère T, Palussière J, Aupérin A et al. Midterm local efficacy and survival after radiofrequency ablation of lung tumors with minimum follow-up of 1 year: prospective evaluation. Radiology 2006; 240: 587-596.
65. Simon CJ, Dupuy DE, DePetrillo TA et al. Pulmonary radiofrequency ablation: long-term safety and efficacy in 153 patients. Radiology 2007; 243: 268-275.
66. Lanuti M, Sharma A, Digumarthy SR et al. Radiofrequency ablation for treatment of medically inoperable stage I non-small cell lung cancer. J Thorac Cardiovasc Surg 2009; 137: 160-166.
67. Pennathur A, Abbas G, Gooding WE et al. Image-guided radiofrequency ablation of lung neoplasm in 100 consecutive patients by a thoracic surgical service. Ann Thorac Surg 2009; 88: 1601-1606.
68. Ambrogi MC, Fanucchi O, Cioni R et al. Long-term results of radiofrequency ablation treatment of stage I non-small cell lung cancer: a prospective intentionto-treat study. J Thorac Oncol 2011; 6: 2044-2051.
69. National Comprehensive Cancer Network. NCCN Guidelines: Senior Adult Oncology, v1. 2013; http://www.nccn.org/professionals/physician_gls/pdf/senior.pdf (24 January 2013, date last accessed).
70. Pepe C, Hasan B, Winton TL et al. Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR 10. J Clin Oncol 2007; 25: 1553-1561.
71. Fruh M, Rolland E, Pignon JP et al. Pooled analysis of the effect of age on adjuvant cisplatin-based chemotherapy for completely resected non-small cell lung cancer. J Clin Oncol 2008; 26: 3573-3581.
72. Wisnivesky JP, Smith CB, Packer S et al. Survival and risk of adverse events in older patients receiving post-operative adjuvant chemotherapy for resected stages II-IIIA lung cancer: observational cohort study. BMJ 2011; 343: d4013.
73. Gu F, Strauss GM, Wisnivesky JP et al. Platinum-based adjuvant chemotherapy (ACT) in elderly patients with non-small cell lung cancer (NSCLC) in the SEERMedicare database: comparison between carboplatin-and cisplatin-based regimens. J Clin Oncol 2011; 29(Suppl): 7014.
74. Fruh M, Shepherd FA. Adjuvant cisplatin-based chemotherapy for elderly patients with completely resected non-small cell lung cancer: review of the evidence. Eur J Clin Med Oncol 2010; 2: 59-63.
75. Fervers B. Chemotherapy in elderly patients with resected stage II-IIIA lung cancer. BMJ 2011; 343: d4104.
76. Lee JH, Machtay M, Kaiser LR et al. Non-small cell lung cancer: prognostic factors in patients treated with surgery and postoperative radiation therapy. Radiology 1999; 213: 845-852.
77. PORT Meta-Analysis Trialists Group. Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. Lancet 1998; 352: 257-263.
78. Dautzenberg B, Arriagada R, Chammard AB et al. Groupe d'Etude et de Traitement des Cancers Bronchiques. A controlled study of postoperative radiotherapy for patients with completely resected nonsmall cell lung carcinoma. Cancer 1999; 86: 265-273.
79. Feng QF, Wang M, Wang LJ et al. A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial. Int J Radiat Oncol Biol Phys 2000; 47: 925-929.
80. Douillard JY, Rosell R, De LM et al. Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol 2006; 7: 719-727.
81. Wisnivesky JP, Halm EA, Bonomi M et al. Postoperative radiotherapy for elderly patients with stage III lung cancer. Cancer 2012; 118: 4478-4485.
82. Hayakawa K, Mitsuhashi N, Katano S et al. High-dose radiation therapy for elderly patients with inoperable or unresectable non-small cell lung cancer. Lung Cancer 2001; 32: 81-88.
83. Dillman RO, Seagren SL, Propert KJ et al. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III nonsmall-cell lung cancer. N Engl J Med 1990; 323: 940-945.
84. Sause WI, Kolesar P, Taylor SIV et al. Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, and Southwest Oncology Group. Chest 2000; 117: 358-364.
85. Furuse KI, Fukuoka M, Kawahara M et al. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol 1999; 17: 2692-2699.
86. Zatloukal PI, Petruzelka L, Zemanova M et al. Concurrent versus sequential chemoradiotherapy with cisplatin and vinorelbine in locally advanced non-small cell lung cancer: a randomized study. Lung Cancer 2004; 46: 87-98.
87. Curran WJJr, Paulus R, Langer CJ et al. Sequential vs. concurrent chemoradiation for stage III non-small cell lung cancer: randomized phase III trial RTOG 9410. J Natl Cancer Inst 2011; 103: 1452-1460.
88. Langer CJ, Hsu C, Curran W et al. Elderly patients ( pts) with locally advanced non-small cell lung cancer (LA-NSCLC) benefit from combined modality therapy: secondary analysis of Radiation Therapy Oncology Group (RTOG) 94-10. Proc Am Soc Clin Oncol 2002; 21: Abstr 1193.
89. Rocha Lima CM, Herndon JE, Kosty M, Clamon G, Green MR. Therapy choices among older patients with lung carcinoma: an evaluation of two trials of the Cancer and Leukemia Group B. Cancer 2002; 94: 181-187.
90. Schild SE, Stella PJ, Geyer SM et al. The outcome of combined-modality therapy for stage III non-small-cell lung cancer in the elderly. J Clin Oncol 2003; 21: 3201-3206.
91. Sgroi MM, Neubauer M, Ansari R et al. An analysis of elderly patients ( pts) treated on a phase III trial of cisplatin (P) plus etoposide (E) with concurrent radiotherapy (CRT) followed by docetaxel (D) vs observation (O) in patients with stage III nonsmall cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2007; 25: 9037.
92. Hardy D, Liu C-C, Cormier JN, Xia R, Du XL. Cardiac toxicity in association with chemotherapy and radiation therapy in a large cohort of older patients with nonsmall cell lung cancer. Ann Oncol 2010; 21: 1825-1833.
93. Jalal SI, Riggs HD, Melnyk A et al. Updated survival and outcomes for older patients with inoperable stage III non-small cell lung cancer treated with etoposide and current chest radiation with or without consolidation docetaxel: analysis of a phase III trial from the Hoosier Oncology Group (HOG) and US Oncology. Ann Oncol 2012; 23: 1730-1738.
94. Westeel V, Quoix E, Baudrin L, Milleron B. Concurrent chemoradiation for elderly patients with locally advanced non-small cell lung cancer: still a controversial issue. Aging Health 2012; 8: 119-122.
95. Semrau S, Bier A, Thierbach U et al. 6-Year experience of concurrent radiochemotherapy with vinorelbine plus a platinum compound in multimorbid or aged patients with inoperable non-small cell lung cancer. Strahlenther Onkol 2007; 192: 30-35.
96. Atagi S, Kawahara M, Yokoyama A et al. Thoracic radiotherapy with and without daily low-dose carboplatin in elderly patients with non-small cell lung cancer: a randomised, controlled phase 3 trial by the Japan Clinical Oncology Group (JCOG0301). Lancet Oncol 2012; 13: 671-678.
97. Lee JH, Wu HG, Kim HJ et al. Influence of comorbidities on the efficacy of radiotherapy with or without chemotherapy in elderly stage III non-small cell lung cancer patients. Cancer Res Treat 2012; 44: 242-250.
98. Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small cell lung cancer. J Natl Cancer Inst 1999; 91: 66-72.
99. Gridelli C. 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.
100. Kudoh S, Takeda K, Nakagawa K et al. Phase III study of docetaxel compared with vinorelbine in elderly patients with advanced non-small cell lung cancer: results of the West Japan Thoracic Oncology Group Trial (WJTOG 9904). J Clin Oncol 2006; 24: 3657-3663.
101. Ramalingam SS, Khuri FR. The role of taxanes in the treatment of older patients with advanced stage non-small cell lung cancer. Oncologist 2009; 14: 412-424.
102. Frasci G, Lorusso V, Panza N et al. Gemcitabine plus vinorelbine yields better survival outcome than vinorelbine alone in elderly patients with advanced nonsmall cell lung cancer. A Southern Italy Cooperative Oncology Group (SICOG) phase III trial. Lung Cancer 2001; 34: S65-S69.
103. Gridelli C, Perrone F, Gallo C et al. Chemotherapy for elderly patients with advanced non-small cell lung cancer: the Multicenter Italian Lung Cancer in the Elderly Study (MILES). J Natl Cancer Inst 2003; 95: 362-372.
104. Comella P, Frasci G, Carnicelli P et al. Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced nonsmall-cell lung cancer patients. Br J Cancer 2004; 91: 489-497.
105. Hainsworth JD, Spigel DR, Farley C et al. Weekly docetaxel versus docetaxel/gemcitabine in the treatment of elderly or poor performance status patients with advanced nonsmall cell lung cancer: a randomized phase 3 trial of the Minnie Pearl Cancer Research Network. Cancer 2007; 110: 2027-2034.
106. Russo A, Rizzo S, Fulfaro F et al. Gemcitabine-based doublets versus singleagent therapy for elderly patients with advanced nonsmall cell lung cancer: a Literature-based Meta-analysis. Cancer 2009; 115: 1924-1931.
107. Pfizer. Gemcitabine Prescribing Information (US). 2011; http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=632a8105-9cb2-44ba-8c10-2a1efd6ac960 (14 January 2014, date last accessed).
108. Hospira. Gemcitabine Summary of Product Characteristics (Europe). 2010; http://www.medicines.org.uk/emc/medicine/23656/spc (14 January 2014, date last accessed).
109. Kelly K, Giarritta S, Hayes S. Should older patients receive combination chemotherapy for advanced stage non-small cell lung cancer? An analysis of Southwest Oncology trials 9509 and 9308. Proc Am Soc Clin Oncol 2001; 20: A-1313. ; 329a.
110. Langer CJ, Manola J, Bernardo P et al. 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.
111. Langer C, Vangel M, Schiller J et al. Age-specific subanalysis of ECOG 1594: fit elderly patients (70-80 yrs) with NSCLC do as well as young pts (<70). Lung Cancer 2003; 41: S17.
112. Hensing TA, Peterman AH, Schell MJ, Lee JH, Socinski MA. The impact of age on toxicity, response rate, quality of life, and survival in patients with advanced, stage IIIB or IV nonsmall cell lung carcinoma treated with carboplatin and paclitaxel. Cancer 2003; 98: 779-788.
113. Belani CP, Fossella F. Elderly subgroup analysis of a randomized phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for firstline treatment of advanced nonsmall cell lung carcinoma (TAX 326). Cancer 2005; 104: 2766-2774.
114. Sederholm C, Hillerdal G, Lamberg K et al. Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: the Swedish Lung Cancer Study Group. J Clin Oncol 2005; 23: 8380-8388.
115. Lilenbaum RC, Herndon JE, II, List MA 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.
116. Goto K, Nishiwaki Y, Saijo N et al. The Four-Arm Cooperative Study (FACS) for advanced non-small cell lung cancer (NSCLC): a subgroup analysis in elderly patients ( pts). J Clin Oncol 2006; 24(Suppl): 115.
117. Ansari RH, Socinski MA, Edelman MJ et al. A retrospective analysis of outcomes by age in a three-arm phase III trial of gemcitabine in combination with carboplatin or paclitaxel vs. paclitaxel plus carboplatin for advanced non-small cell lung cancer. Crit Rev Oncol Hematol 2011; 78: 162-171.
118. Blanchard EM, Moon J, Hesketh PJ et al. Comparison of platinum-based chemotherapy in patients older and younger than 70 years: an analysis of Southwest Oncology Group Trials 9308 and 9509. J Thorac Oncol 2011; 6: 115-120.
119. Lippe P, Tummarello D, Monterubbianesi MC et al. Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase II study. Ann Oncol 1999; 10: 217-221.
120. Mattioli R, Morese R, Imperatori L et al. Weekly cisplatin (P) and vinorelbine (V) is active, manageable and provides clinical benefit in advanced non-small cell lung cancer (ANSCLC) elderly or poor performance status (PS) patients. Ann Oncol 2002; 13(Suppl 5): 104.
121. Feliu J, Martin G, Madronal C et al. Combination of low-dose cisplatin and gemcitabine for treatment of elderly patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol 2003; 52: 247-252.
122. Berardi R, Porfiri E, Scartozzi M et al. Elderly patients with advanced non-small cell lung cancer. A phase II study with weekly cisplatin and gemcitabine. Oncology 2003; 65: 198-203.
123. Ohe Y, Niho S, Kakinuma R et al. A phase II study of cisplatin and docetaxel administered as three consecutive weekly infusions for advanced non-small-cell lung cancer in elderly patients. Ann Oncol 2004; 15: 45-50.
124. Feliu J, Firvida JL, Castro J et al. Oncopaz Cooperative Group. Combination therapy with docetaxel and low dose of cisplatin in elderly patients with advanced non-small cell lung cancer: multicenter phase II study. Cancer Chemother Pharmacol 2009; 63: 403-409.
125. Quoix E, Zalcman G, Oster J-P. Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomized, phase 3 trial. Lancet 2011; 378: 1079-1088.
126. Brunello A, Loaldi E, Balducci L. Dose adjustment and supportive care before and during treatment. Cancer Treat Rev 2009; 35: 493-498.
127. Merino-Sanjuán M, Monteiro JF, Porta-Oltra B et al. Effect of age on systemic exposure and haematological toxicity of carboplatin in advanced non-small cell lung cancer patients. Basic Clin Pharmacol Toxicol 2011; 109: 457-464.
128. Qi W-X, Tang L-N, He A-N. Doublet versus single cytotoxic agent as first-line treatment for elderly patients with advanced non-small cell lung cancer: a systematic review and meta-analysis. Lung 2012; 190: 477-485.
129. Corre R, Decroistte C, Grellier L et al. Phase III, randomized, multicenter study comparing in elderly patients (=70 years) with stage IV non small-cell lung cancer (NSCLC) a standard strategy of treatment allocation (carboplatin based bitherapy or monotherapy with docetaxel) based on performance status (PS) and age with an experimental strategy allocating the same chemotherapies or best supportive care (BSC) according to a comprehensive geriatric assessment (CGA). J Thorac Oncol 2013; 8(Suppl 2): S192.
130. Weiss GJ, Langer C, Rosell R et al. Elderly patients benefit from second-line cytotoxic chemotherapy: a subset analysis of a randomized phase III trial of pemetrexed compared with docetaxel in patients with previously treated advanced non-small-cell lung cancer. J Clin Oncol 2006; 24: 4405-4411.
131. 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: 2542-2550.
132. Ramalingam SS, Dahlberg SE, Langer CJ et al. Outcomes for elderly, advancedstage 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.
133. Zhu J, Sharma DB, Gray SW et al. Carboplatin and paclitaxel with vs. without bevacizumab in older patients with advanced non-small cell lung cancer. JAMA 2012; 307: 1593-1601.
134. Laskin J, Crino L, Felip E et al. Safety and efficacy of first-line bevacizumab plus chemotherapy in elderly patients with advanced or recurrent non-squamous nonsmall cell lung cancer: safety of avastin in lung trial (MO19390). J Thorac Oncol 2012; 7: 203-211.
135. Wakelee HA, Dahlberg SE, Brahmer JR et al. Increased benefit from bevacizumab (BEV) in younger women with advanced NSCLC on Eastern Cooperative Oncology Group (ECOG) E4599. J Thorac Oncol 2008; 3(Suppl 4 11): S282.
136. Leighl NB, Zatloukal P, Mezger J et al. Efficacy and safety of bevacizumab-based therapy in elderly patients with advanced or recurrent nonsquamous non-small cell lung cancer in the phase III BO17704 study (AVAiL). J Thorac Oncol 2010; 5: 1970-1976.
137. Langer CJ, Socinski MA, Patel JD et al. Efficacy and safety of paclitaxel and carboplatin with bevacizumab for the first-line treatment of patients with nonsquamous non-small cell lung cancer (NSCLC): analyses based on age in the phase III PointBreak and E4599 trials. J Clin Oncol 2013; 31(Suppl): abstr 8073.
138. Maemondo M, Minegishi Y, Inoue A et al. First-line gefitinib in patients aged 75 or older with advanced non-small cell lung cancer harboring epidermal growth factor receptor mutations: NEJ 003 study. J Thorac Oncol 2012; 7: 1417-1422.
139. Tateishi I, Ichiyama T, Hira K et al. Clinical outcomes in elderly patients administered gefitinib as first-line treatment in epidermal growth factor receptormutated non-small-cell lung cancer: retrospective analysis in a Nagano Lung Cancer Research Group study. Med Oncol 2013; 30: 450.
140. Lin C-C, Yang C-H. Epidermal growth factor receptor tyrosine kinase inhibitors in elderly or poor performance status patients with advanced non-small cell lung cancer. Targ Oncol 2009; 4: 37-44.
141. Quoix E, Westeel V, Moreau L et al. Second-line therapy in elderly patients with advanced nonsmallcell lung cancer. Eur Respir J 2014; 43: 240-249.
142. 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.
143. Scheffler M, Di Gion P, Doroshyenko O, Fuhr U. Clinical pharmacokinetics of tyrosine kinase inhibitors: focus on 4-anilinoquinazolines. Clin Pharmacokinet 2011; 50: 371-403.
144. Temel JS, Greer JA, Muzikansky A et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010; 363: 733-742.
145. Aapro MSA, Bohlius J, Cameron DA et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer 2011; 47: 8-32.
146. Ludwig H, Van Belle S, Barrett-Lee P et al. The European Cancer Anaemia Survey (ECAS): a large multicentre, prospective survey defining the prevalence, incidence and treatment of anaemia in cancer patients. Eur J Cancer 2004; 40: 2293-2306.
147. National Comprehensive Cancer Network. NCCN Guidelines: Cancer-and Chemotherapy-Induced Anemia, v2.2014; http://www.nccn.org/professionals/physician_gls/pdf/anemia.pdf (22 August 2013, date last accessed).
148. Auerbach M, Ballard H, Trout JR et al. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy related anemia: a multicenter, open-label, randomized trial. J Clin Oncol 2004; 22: 1301-1307.
149. Bastit L, Vandebroek A, Altintas S et al. Randomized multicenter controlled trial comparing the efficacy and safety of darbepoetin alfa administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. J Clin Oncol 2008; 26: 1611-1618.
150. Pedrazzoli P, Farris A, Del Prete S et al. Randomized trial of intravenous iron supplementation in patients with chemotherapy related anemia without iron deficiency treated with darbepoetin alpha. J Clin Oncol 2008; 26: 1619-1625.
151. Jakobsen JN, Herrstedt J. Prevention of chemotherapy-induced nausea and vomiting in elderly cancer patients. Crit Rev Oncol Hematol 2009; 71: 214-221.
152. Aapro M, Johnson J. Chemotherapy-induced emesis in elderly cancer patients: the role of 5-HT3-receptor antagonists in the first 24 hours. Gerontology 2005; 51: 287-296.
153. Hutchins LF, Unger JM, Crowley JJ, Coltman CA, Jr, Albain KS. Underrepresentation of patients 65 years of age or older in cancer-treatment trials. N Engl J Med 1999; 341: 2061-2067.
154. Talarico L, Chen G, Pazdur R. Enrollment of elderly patients in clinical trials for cancer drug registration: a 7-year experience by the US Food and Drug Administration. J Clin Oncol 2004; 22: 4626-4631.
155. Payne JK, Hendrix CC. Clinical trial recruitment challenges with older adults with cancer. Appl Nurs Res 2010; 23: 233-237.
156. Scher KS, Hurria A. Under-representation of older adults in cancer registration trials: known problem, little progress. J Clin Oncol 2012; 30: 2036-2038.
157. Pallis AG, Ring A, Fortpied C et al. European Organisation for Research and Treatment of Cancer Elderly Task Force. EORTC workshop on clinical trial methodology in older individuals with a diagnosis of solid tumors. Ann Oncol 2011; 22: 1922-1926.
158. Sacher AG, Le LW, Leigh NB, Coate LE. Elderly patients with advanced NSCLC in phase III clinical trials: are the elderly excluded from practice-changing trials in advanced NSCLC? J Thorac Oncol 2013; 8: 366-368.
159. Townsley CA, Selby R, Siu LL. Systematic review of barriers to the recruitment of older patients with cancer onto clinical trials. J Clin Oncol 2005; 23: 3112-3124.
160. Townsley CA, Chan KK, Pond GR et al. Understanding the attitudes of the elderly towards enrolment into cancer clinical trials. BMC Cancer 2006; 6: 34.
161. Basche M, Baron A, Eckhardt SG et al. Barriers to enrollment of elderly adults in early-phase cancer clinical trials. J Oncol Pract 2008; 4: 162-168.
162. Lichtman SM. Clinical trial design in older adults with cancer-the need for new paradigms. J Geriatr Oncol 2012; 3: 368-375.
163. Hurria A, Cohen HJ, Extermann M. Geriatric Oncology Research in the Cooperative Groups: a report of a SIOG special meeting. J Geriatr Oncol 2010; 1: 40-44.
164. Pazdur R. Endpoints for assessing drug activity in clinical trials. Oncologist 2008; 13: 19-21.
165. Wildiers H, Mauer M, Pallis A et al. End points and trial design in geriatric oncology research: a Joint European Organisation for Research and Treatment of Cancer-Alliance for Clinical Trials in Oncology-International Society of Geriatric Oncology position article. J Clin Oncol 2013; 31: 3711-3718.