Download PDF
Semin Respir Crit Care Med 2005; 26(3): 289-297
DOI: 10.1055/s-2005-871987
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Treatment of Advanced Non-Small Cell Lung Cancer in the Elderly

Lecia V. Sequist1 , Panos Fidias1
  • 1Center for Thoracic Cancers, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts
Further Information

Publication History

Publication Date:
29 June 2005 (online)

    Permissions and Reprints

ABSTRACT

Non-small cell lung cancer (NSCLC) is primarily a disease of the elderly. Although NSCLC is the leading cause of cancer death in the United States and the overall prognosis of this disease is poor, treatment improves survival compared with best supportive care, independent of the stage of disease. Elderly patients have a particularly poor prognosis with NSCLC compared with younger patients, likely due to age-related biases in referral and treatment patterns. There is an emerging literature regarding the tolerability of NSCLC treatments in elderly patients. In advanced disease, subgroup analyses of the elderly population participating in randomized clinical trials as well as elder-specific prospective randomized trials have demonstrated that elderly NSCLC patients derive equivalent survival benefit from the treatment of NSCLC as younger patients. This treatment is tolerable for “fit” elderly patients, and modified regimens are available for the more frail elderly patients. Evaluating the relative fitness of an elderly patient may be achieved through an assessment of functional ability. As the U.S. population ages and the incidence of NSCLC rises, an understanding of treatment options for elderly patients with NSCLC is vital for all clinicians involved in their clinical care.

KEYWORDS

Non-small cell lung cancer - elderly - comprehensive geriatric assessment

REFERENCES

  • 1 US Census Bureau .US interim projections by age, race, sex and Hispanic origin. Available at: http://www.census.gov/ipc/www/usinterimproj/. Accessed January 25, 2005. 
    Google Scholar
  • 2 American Cancer Society .Cancer Statistics 2005 Presentation. Available at: http://www.cancer.org/docroot/PRO/content/PRO_1_1_Cancer_Statistics_2005_Presentation.asp. Accessed January 25, 2005. 
    Google Scholar
  • 3 Yancik R. Cancer burden in the aged: an epidemiologic and demographic overview.  Cancer. 1997;  80 1273-1283
    CrossrefPubMedGoogle Scholar
  • 4 Hurria A, Kris M G. Management of lung cancer in older adults.  CA Cancer J Clin. 2003;  53 325-341
    PubMedGoogle Scholar
  • 5 Brundage M D, Davies D, Mackillop W J. Prognostic factors in non-small cell lung cancer: a decade of progress.  Chest. 2002;  122 1037-1057
    CrossrefPubMedGoogle Scholar
  • 6 Wertzel H, Siebert H, Lange W, Swoboda L, Graf E, Hasse J. Results after surgery in stage-I bronchogenic carcinoma.  Thorac Cardiovasc Surg. 1998;  46 365-369
    PubMedGoogle Scholar
  • 7 Diez M, Torres A, Maestro M L et al.. Prediction of survival and recurrence by serum and cytosolic levels of CEA, CA125 and SCC antigens in resectable non-small-cell lung cancer.  Br J Cancer. 1996;  73 1248-1254
    PubMedGoogle Scholar
  • 8 Mori M, Kohli A, Baker S P, Savas L, Fraire A E. Laminin and cathepsin B as prognostic factors in stage I non-small cell lung cancer: are they useful?.  Mod Pathol. 1997;  10 572-577
    PubMedGoogle Scholar
  • 9 Fontanini G, Lucchi M, Vignati S et al.. Angiogenesis as a prognostic indicator of survival in non-small-cell lung carcinoma: a prospective study.  J Natl Cancer Inst. 1997;  89 881-886
    CrossrefPubMedGoogle Scholar
  • 10 Mountain C F. Revisions in the International System for Staging Lung Cancer.  Chest. 1997;  111 1710-1717
    CrossrefPubMedGoogle Scholar
  • 11 O’Rourke M A, Feussner J R, Feigl P, Laszlo J. Age trends of lung cancer stage at diagnosis: implications for lung cancer screening in the elderly.  JAMA. 1987;  258 921-926
    CrossrefPubMedGoogle Scholar
  • 12 Nugent W C, Edney M T, Hammerness P G, Dain B J, Maurer L H, Rigas J R. Non-small cell lung cancer at the extremes of age: impact on diagnosis and treatment.  Ann Thorac Surg. 1997;  63 193-197
    CrossrefPubMedGoogle Scholar
  • 13 Spira A, Ettinger D S. Multidisciplinary management of lung cancer.  N Engl J Med. 2004;  350 379-392
    CrossrefPubMedGoogle Scholar
  • 14 Bunn Jr P A. Chemotherapy for advanced non-small-cell lung cancer: who, what, when, why?.  J Clin Oncol. 2002;  20(18 Suppl) 23S-33S
    PubMedGoogle Scholar
  • 15 Townsley C A, Naidoo K, Pond G R, Melnick W, Straus S E, Siu L L. Are older cancer patients being referred to oncologists? A mail questionnaire of Ontario primary care practitioners to evaluate their referral patterns.  J Clin Oncol. 2003;  21 4627-4635
    CrossrefPubMedGoogle Scholar
  • 16 Yellen S B, Cella D F, Leslie W T. Age and clinical decision making in oncology patients.  J Natl Cancer Inst. 1994;  86 1766-1770
    PubMedGoogle Scholar
  • 17 Silvestri G, Pritchard R, Welch H G. Preferences for chemotherapy in patients with advanced non-small cell lung cancer: descriptive study based on scripted interviews.  BMJ. 1998;  317 771-775
    PubMedGoogle Scholar
  • 18 Smith T J, Penberthy L, Desch C E et al.. Differences in initial treatment patterns and outcomes of lung cancer in the elderly.  Lung Cancer. 1995;  13 235-252
    CrossrefPubMedGoogle Scholar
  • 19 Dillman R O, Seagren S L, Propert K J et al.. A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small-cell lung cancer.  N Engl J Med. 1990;  323 940-945
    CrossrefPubMedGoogle Scholar
  • 20 Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. Non-small Cell Lung Cancer Collaborative Group.  BMJ. 1995;  311 899-909
    Google Scholar
  • 21 Movsas B, Moughan J, Komaki R et al.. Radiotherapy patterns of care study in lung carcinoma.  J Clin Oncol. 2003;  21 4553-4559
    CrossrefPubMedGoogle Scholar
  • 22 Earle C C, Neumann P J, Gelber R D, Weinstein M C, Weeks J C. Impact of referral patterns on the use of chemotherapy for lung cancer.  J Clin Oncol. 2002;  20 1786-1792
    CrossrefPubMedGoogle Scholar
  • 23 Hillner B E, McDonald M K, Desch C E, Smith T J, Penberthy L T, Retchin S M. A comparison of patterns of care of nonsmall cell lung carcinoma patients in a younger and Medigap commercially insured cohort.  Cancer. 1998;  83 1930-1937
    CrossrefPubMedGoogle Scholar
  • 24 Finkelstein D M, Ettinger D S, Ruckdeschel J C. Long-term survivors in metastatic non-small-cell lung cancer: an Eastern Cooperative Oncology Group Study.  J Clin Oncol. 1986;  4 702-709
    PubMedGoogle Scholar
  • 25 Stanley K E. Prognostic factors for survival in patients with inoperable lung cancer.  J Natl Cancer Inst. 1980;  65 25-32
    PubMedGoogle Scholar
  • 26 Socinski M A, Zhang C, Herndon II J E et al.. Combined modality trials of the Cancer and Leukemia Group B in stage III non-small-cell lung cancer: analysis of factors influencing survival and toxicity.  Ann Oncol. 2004;  15 1033-1041
    CrossrefPubMedGoogle Scholar
  • 27 Albain K S, Crowley J J, LeBlanc M, Livingston R B. Survival determinants in extensive-stage non-small-cell lung cancer: the Southwest Oncology Group experience.  J Clin Oncol. 1991;  9 1618-1626
    PubMedGoogle Scholar
  • 28 Hutchins L F, Unger J M, Crowley J J, Coltman Jr C A, Albain K S. Underrepresentation of patients 65 years of age or older in cancer-treatment trials.  N Engl J Med. 1999;  341 2061-2067
    CrossrefPubMedGoogle Scholar
  • 29 Murthy V H, Krumholz H M, Gross C P. Participation in cancer clinical trials: race-, sex-, and age-based disparities.  JAMA. 2004;  291 2720-2726
    CrossrefPubMedGoogle Scholar
  • 30 Lewis J H, Kilgore M L, Goldman D P et al.. Participation of patients 65 years of age or older in cancer clinical trials.  J Clin Oncol. 2003;  21 1383-1389
    CrossrefPubMedGoogle Scholar
  • 31 Yee K W, Pater J L, Pho L, Zee B, Siu L L. Enrollment of older patients in cancer treatment trials in Canada: why is age a barrier?.  J Clin Oncol. 2003;  21 1618-1623
    CrossrefPubMedGoogle Scholar
  • 32 Weinmann M, Jeremic B, Toomes H, Friedel G, Bamberg M. Treatment of lung cancer in the elderly, I: Non-small cell lung cancer.  Lung Cancer. 2003;  39 233-253
    CrossrefPubMedGoogle Scholar
  • 33 Pagni S, Federico J A, Ponn R B. Pulmonary resection for lung cancer in octogenarians.  Ann Thorac Surg. 1997;  63 785-789
    CrossrefPubMedGoogle Scholar
  • 34 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
    CrossrefPubMedGoogle Scholar
  • 35 Dyszkiewicz W, Pawlak K, Gasiorowski L. Early post-pneumonectomy complications in the elderly.  Eur J Cardiothorac Surg. 2000;  17 246-250
    CrossrefPubMedGoogle Scholar
  • 36 van Rens M T, de la Riviere A B, Elbers H R, van Den Bosch J M. Prognostic assessment of 2,361 patients who underwent pulmonary resection for non-small cell lung cancer, stage I, II, and IIIA.  Chest. 2000;  117 374-379
    CrossrefPubMedGoogle Scholar
  • 37 Jazieh A R, Hussain M, Howington J A et al.. Prognostic factors in patients with surgically resected stages I and II non-small cell lung cancer.  Ann Thorac Surg. 2000;  70 1168-1171
    CrossrefPubMedGoogle Scholar
  • 38 Bach P B, Cramer L D, Schrag D, Downey R J, Gelfand S E, Begg C B. The influence of hospital volume on survival after resection for lung cancer.  N Engl J Med. 2001;  345 181-188
    CrossrefPubMedGoogle Scholar
  • 39 Pignon T, Gregor A, Schaake Koning C, Roussel A, Van Glabbeke M, Scalliet P. Age has no impact on acute and late toxicity of curative thoracic radiotherapy.  Radiother Oncol. 1998;  46 239-248
    CrossrefPubMedGoogle Scholar
  • 40 Singh A K, Lockett M A, Bradley J D. Predictors of radiation-induced esophageal toxicity in patients with non-small-cell lung cancer treated with three-dimensional conformal radiotherapy.  Int J Radiat Oncol Biol Physiol. 2003;  55 337-341
    PubMedGoogle Scholar
  • 41 Schild S E, Stella P J, Geyer S M 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
    CrossrefPubMedGoogle Scholar
  • 42 Rocha Lima C M, Herndon II J E, Kosty M, Clamon G, Green M R. 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
    CrossrefPubMedGoogle Scholar
  • 43 Langer C J, Hsu C, Curran W J 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. Paper presented at: American Society of Clinical Oncology 2002 Orlando, FL; Abstract 1193
    Google Scholar
  • 44 Brundage M D, Davidson J R, Mackillop W J. Trading treatment toxicity for survival in locally advanced non-small cell lung cancer.  J Clin Oncol. 1997;  15 330-340
    PubMedGoogle Scholar
  • 45 Fried T R, Bradley E H, Towle V R, Allore H. Understanding the treatment preferences of seriously ill patients.  N Engl J Med. 2002;  346 1061-1066
    CrossrefPubMedGoogle Scholar
  • 46 Pfister D G, Johnson D H, Azzoli C G et al.. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003.  J Clin Oncol. 2004;  22 330-353
    CrossrefPubMedGoogle Scholar
  • 47 Rapp E, Pater J L, Willan A et al.. Chemotherapy can prolong survival in patients with advanced non-small-cell lung cancer: report of a Canadian multicenter randomized trial.  J Clin Oncol. 1988;  6 633-641
    PubMedGoogle Scholar
  • 48 Cullen M H, Billingham L J, Woodroffe C M et al.. Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life.  J Clin Oncol. 1999;  17 3188-3194
    PubMedGoogle Scholar
  • 49 Stephens R J, Fairlamb D, Gower N H et al.. The Big Lung Trial (BLT): determining the value of cisplatin-based chemotherapy for all patients with non-small cell lung cancer (NSCLC). Preliminary results in the supportive care setting. Paper presented at: American Society of Clinical Oncology 2002 Orlando, FL; Abstract 1161
    Google Scholar
  • 50 Le Chevalier T, Brisgand D, Douillard J Y et al.. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients.  J Clin Oncol. 1994;  12 360-367
    PubMedGoogle Scholar
  • 51 Wozniak A J, Crowley J J, Balcerzak S P et al.. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study.  J Clin Oncol. 1998;  16 2459-2465
    PubMedGoogle Scholar
  • 52 Cardenal F, Lopez-Cabrerizo M P, Anton A et al.. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer.  J Clin Oncol. 1999;  17 12-18
    PubMedGoogle Scholar
  • 53 Bonomi P, Kim K, Fairclough D et al.. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial.  J Clin Oncol. 2000;  18 623-631
    PubMedGoogle Scholar
  • 54 Go R S, Adjei A A. Review of the comparative pharmacology and clinical activity of cisplatin and carboplatin.  J Clin Oncol. 1999;  17 409-422
    PubMedGoogle Scholar
  • 55 Schiller J H, Harrington D, Belani C P et al.. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.  N Engl J Med. 2002;  346 92-98
    CrossrefPubMedGoogle Scholar
  • 56 Georgoulias V, Papadakis E, Alexopoulos A et al.. Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial.  Lancet. 2001;  357 1478-1484
    CrossrefPubMedGoogle Scholar
  • 57 Kosmidis P, Mylonakis N, Nicolaides C et al.. Paclitaxel plus carboplatin versus gemcitabine plus paclitaxel in advanced non-small-cell lung cancer: a phase III randomized trial.  J Clin Oncol. 2002;  20 3578-3585
    CrossrefPubMedGoogle Scholar
  • 58 Langer C J, 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
    PubMedGoogle Scholar
  • 59 Langer C J, Vangel M, Schiller J H et al.. Age-specific subanalysis of ECOG 1594: fit elderly patients (70-80 yrs) with NSCLC do as well as younger pts (< 70). Paper presented at: American Society of Clinical Oncology 2003 Chicago, IL; Abstract 2571
    Google Scholar
  • 60 Kelly K, Giarritta S, Akerley W et al.. Should older patients (pts) receive combination chemotherapy for advanced stage non-small cell lung cancer (NSCLC)? An analysis of Southwest Oncology Trials 9509 and 9308. Paper presented at: American Society of Clinical Oncology 2001 San Francisco, CA; Abstract 1313
    Google Scholar
  • 61 Hensing T A, Peterman A H, Schell M J, Lee J H, Socinski M A. The impact of age on toxicity, response rate, quality of life, and survival in patients with advanced, stage IIIB or IV non-small cell lung carcinoma treated with carboplatin and paclitaxel.  Cancer. 2003;  98 779-788
    CrossrefPubMedGoogle Scholar
  • 62 Fossella F V, Belani C P. Phase III study (TAX 326) of docetaxel-cisplatin (DC) and docetaxel-carboplatin (DCb) versus vinorelbine-cisplatin (VC) for the first-line treatment of advanced/metastatic non-small-cell lung cancer (NSCLC): Analysis in elderly patients. Paper presented at: American Society of Clinical Oncology 2003 Chicago, IL; Abstract 2528
    Google Scholar
  • 63 Lilenbaum R C, Herndon II J E, List M A 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
    PubMedGoogle Scholar
  • 64 Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. The Elderly Lung Cancer Vinorelbine Italian Study Group.  J Natl Cancer Inst. 1999;  91 66-72
    CrossrefPubMedGoogle Scholar
  • 65 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
    PubMedGoogle Scholar
  • 66 Frasci G, Lorusso V, Panza N 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
    PubMedGoogle Scholar
  • 67 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) phase III randomized trial.  J Natl Cancer Inst. 2003;  95 362-372
    PubMedGoogle Scholar
  • 68 Balducci L, Extermann M. Management of cancer in the older person: a practical approach.  Oncologist. 2000;  5 224-237
    CrossrefPubMedGoogle Scholar
  • 69 Balducci L, Beghe C. The application of the principles of geriatrics to the management of the older person with cancer.  Crit Rev Oncol Hematol. 2000;  35 147-154
    PubMedGoogle Scholar
  • 70 Stuck A E, Siu A L, Wieland G D, Adams J, Rubenstein L Z. Comprehensive geriatric assessment: a meta-analysis of controlled trials.  Lancet. 1993;  342 1032-1036
    CrossrefPubMedGoogle Scholar
  • 71 Rich M W, Beckham V, Wittenberg C, Leven C L, Freedland K E, Carney R M. A multidisciplinary intervention to prevent the readmission of elderly patients with congestive heart failure.  N Engl J Med. 1995;  333 1190-1195
    CrossrefPubMedGoogle Scholar
  • 72 Repetto L, Comandini D. Cancer in the elderly: assessing patients for fitness.  Crit Rev Oncol Hematol. 2000;  35 155-160
    PubMedGoogle Scholar
  • 73 Solomon D, Sue Brown A, Brummel-Smith K et al.. Best paper of the 1980s: National Institutes of Health Consensus Development Conference Statement: geriatric assessment methods for clinical decision-making. 1988.  J Am Geriatr Soc. 2003;  51 1490-1494
    CrossrefPubMedGoogle Scholar
  • 74 Repetto L, Fratino L, Audisio R A 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
    CrossrefPubMedGoogle Scholar
  • 75 Extermann M. Comprehensive geriatric assessment basics for the cancer professional.  J Oncol Manag. 2003;  12 13-17
    PubMedGoogle Scholar
  • 76 Basso U, Monfardini S. Multidimensional geriatric evaluation in elderly cancer patients: a practical approach.  Eur J Cancer Care (Engl). 2004;  13 424-433
    CrossrefPubMedGoogle Scholar
  • 77 Zagonel V, Fratino L, Piselli P et al.. The comprehensive geriatric assessment (CGA) predicts mortality among elderly cancer patients (ECP). Paper presented at: American Society of Clinical Oncology 2002 Orlando, FL; Abstract 1458
    Google Scholar
  • 78 Gillespie T W, Patterson H, Harris W B et al.. Improving clinical outcomes in elderly oncology patients. Paper presented at: American Society of Clinical Oncology 2004 New Orleans, LA; Abstract 6075
    Google Scholar
  • 79 Ribeiro M J, Patterson H, Shumate M et al.. Compliance with guidelines for elderly patients undergoing cancer therapy. Paper presented at: American Society of Clinical Oncology 2004 New Orleans, LA; Abstract 6148
    Google Scholar
  • 80 Siegel A B, Fiore J M, Ketas J C et al.. Novel functional assessment techniques for geriatric lymphoma patients. Paper presented at: American Society of Clinical Oncology 2004 New Orleans, LA; Abstract 8166
    Google Scholar
  • 81 Hurria A, Gupta S, Zauderer M et al.. Development of a comprehensive geriatric assessment (CGA) measure for older patients (pts) with cancer: a feasibility study. Paper presented at: American Society of Clinical Oncology 2004 New Orleans, LA; Abstract 8162
    Google Scholar
  • 82 Saliba D, Elliott M, Rubenstein L Z et al.. The Vulnerable Elders Survey: a tool for identifying vulnerable older people in the community.  J Am Geriatr Soc. 2001;  49 1691-1699
    CrossrefPubMedGoogle Scholar

Lecia V SequistM.D. 

Massachusetts General Hospital Cancer Center

Yawkey Center for Outpatient Care

32 Fruit St., 7th fl., Boston, MA 02114

Email: LVSequist@Partners.org

      >