Skip to main content
SpringerLink
Log in

Management of Advanced Non-small Cell Lung Cancer: Front Line Treatment

  • Chapter
  • First Online:
Lung Cancer

Part of the book series: Current Clinical Oncology ((CCO))

  • 2243 Accesses

Abstract

Over the past decades, a number of systemic treatment options for incurable, advanced non-small cell lung cancer have been developed. While untreated patients with this disease typically have a median overall survival of 4.5 months, this figure has exceeded the 12-month mark in the latest randomized phase III trials. Progress in drug development, combination chemotherapy, supportive care, and better selection of patients for specific treatments have contributed to improvements in outcome. In this chapter, we will present the key data that support the use of chemotherapy and biologic agents for the first-line treatment of advanced NSCLC. The following aspects will be discussed: selection and number of chemotherapy agents, duration of therapy, use of biologic drugs (i.e., vascular endothelial growth factor and epidermal growth factor receptor inhibitors), and management of elderly and poor performance status patients.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Bulzebruck H, Bopp R, Drings P et al (1992) New aspects in the staging of lung cancer. Prospective validation of the International Union Against Cancer TNM classification. Cancer 70(5):1102-1110

    Article  PubMed  CAS  Google Scholar 

  2. Mountain CF (1997) Revisions in the international system for staging lung cancer. Chest 111(6):1710-1717

    Article  PubMed  CAS  Google Scholar 

  3. Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355(24):2542-2550

    Article  PubMed  CAS  Google Scholar 

  4. Socinski MA, Morris DE, Masters GA, Lilenbaum R (2003) Chemotherapeutic management of stage IV non-small cell lung cancer. Chest 123(1 Suppl):226S-243S

    Article  PubMed  Google Scholar 

  5. Marino P, Pampallona S, Preatoni A, Cantoni A, Invernizzi F (1994) Chemotherapy vs supportive care in advanced non-small-cell lung cancer. Results of a meta-analysis of the literature. Chest 106(3):861-865

    Article  PubMed  CAS  Google Scholar 

  6. Souquet PJ, Chauvin F, Boissel JP et al (1993) Polychemotherapy in advanced non small cell lung cancer: a meta-analysis. Lancet 342(8862):19-21

    Article  PubMed  CAS  Google Scholar 

  7. Grilli R, Oxman AD, Julian JA (1993) Chemotherapy for advanced non-small-cell lung cancer: how much benefit is enough? J Clin Oncol 11(10):1866-1872

    PubMed  CAS  Google Scholar 

  8. NSCLC Meta-Analyses Collaborative Group (2008) Chemotherapy in addition to supportive care improves survival in advanced non-small-cell lung cancer: a systematic review and meta-analysis of individual patient data from 16 randomized controlled trials. J Clin Oncol 26(28):4617-4625

    Article  Google Scholar 

  9. (1995) 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 311(7010):899-909

    Google Scholar 

  10. Brown J, Thorpe H, Napp V et al (2005) Assessment of quality of life in the supportive care setting of the big lung trial in non-small-cell lung cancer. J Clin Oncol 23(30):7417-7427

    Article  PubMed  CAS  Google Scholar 

  11. Helsing M, Bergman B, Thaning L, Hero U (1998) Quality of life and survival in patients with advanced non-small cell lung cancer receiving supportive care plus chemotherapy with carboplatin and etoposide or supportive care only. A multicentre randomised phase III trial. Joint Lung Cancer Study Group. Eur J Cancer 34(7):1036-1044

    Article  PubMed  CAS  Google Scholar 

  12. Cullen MH, Billingham LJ, Woodroffe CM et al (1999) Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life. J Clin Oncol 17(10):3188-3194

    PubMed  CAS  Google Scholar 

  13. Anderson H, Hopwood P, Stephens RJ, et al (2000) Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer - a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer. Br J Cancer 83(4):447-453

    Article  PubMed  CAS  Google Scholar 

  14. (1999) 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 91(1):66-72

    Google Scholar 

  15. Ranson M, Davidson N, Nicolson M et al (2000) Randomized trial of paclitaxel plus supportive care versus supportive care for patients with advanced non-small-cell lung cancer. J Natl Cancer Inst 92(13):1074-1080

    Article  PubMed  CAS  Google Scholar 

  16. Lilenbaum RC, Langenberg P, Dickersin K (1998) Single agent versus combination chemotherapy in patients with advanced nonsmall cell lung carcinoma: a meta-analysis of response, toxicity, and survival. Cancer 82(1):116-126

    Article  PubMed  CAS  Google Scholar 

  17. Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M (2004) Addition of platinum compounds to a new agent in patients with advanced non-small-cell lung cancer: a literature based meta-analysis of randomised trials. Ann Oncol 15(12):1782-1789

    Article  PubMed  CAS  Google Scholar 

  18. Delbaldo C, Michiels S, Syz N, Soria JC, Le Chevalier T, Pignon JP (2004) Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA 292(4):470-484

    Article  PubMed  CAS  Google Scholar 

  19. Gatzemeier U, von Pawel J, Gottfried M et al (2000) Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 18(19):3390-3399

    PubMed  CAS  Google Scholar 

  20. Sandler AB, Nemunaitis J, Denham C et al (2000) Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 18(1):122-130

    PubMed  CAS  Google Scholar 

  21. Wozniak AJ, Crowley JJ, Balcerzak SP et al (1998) 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 16(7):2459-2465

    PubMed  CAS  Google Scholar 

  22. Lilenbaum RC, Herndon JE 2nd, List MA et al (2005) Single-agent versus combination chemotherapy in advanced non-small-cell lung cancer: the cancer and leukemia group B (study 9730). J Clin Oncol 23(1):190-196

    Article  PubMed  CAS  Google Scholar 

  23. Georgoulias V, Ardavanis A, Agelidou A et al (2004) Docetaxel versus docetaxel plus cisplatin as front-line treatment of patients with advanced non-small-cell lung cancer: a randomized, multicenter phase III trial. J Clin Oncol 22(13):2602-2609

    Article  PubMed  CAS  Google Scholar 

  24. Sederholm C, Hillerdal G, Lamberg K et al (2005) 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 23(33):8380-8388

    Article  PubMed  Google Scholar 

  25. Finkelstein DM, Ettinger DS, Ruckdeschel JC (1986) Long-term survivors in metastatic non-small-cell lung cancer: an Eastern Cooperative Oncology Group Study. J Clin Oncol 4(5):702-709

    PubMed  CAS  Google Scholar 

  26. Bonomi P, Kim K, Fairclough D et al (2000) 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 18(3):623-631

    PubMed  CAS  Google Scholar 

  27. Kelly K, Crowley J, Bunn PA Jr et al (2001) Randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer: a Southwest Oncology Group trial. J Clin Oncol 19(13):3210-3218

    PubMed  CAS  Google Scholar 

  28. Schiller JH, Harrington D, Belani CP et al (2002) Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 346(2):92-98

    Article  PubMed  CAS  Google Scholar 

  29. Fossella F, Pereira JR, von Pawel J et al (2003) Randomized, multinational, phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for advanced non-small-cell lung cancer: the TAX 326 study group. J Clin Oncol 21(16):3016-3024

    Article  PubMed  CAS  Google Scholar 

  30. Scagliotti GV, Parikh P, von Pawel J et al (2008) 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 26(21):3543-3551

    Article  PubMed  CAS  Google Scholar 

  31. Ciuleanu TE, Brodowicz T, Belani CP, et al (2008) Maintenance pemetrexed plus best supportive care (BSC) versus placebo plus BSC: a phase III study. J Clin Oncol 26 (abstract no. 8011)

    Google Scholar 

  32. Ceppi P, Volante M, Saviozzi S et al (2006) Squamous cell carcinoma of the lung compared with other histotypes shows higher messenger RNA and protein levels for thymidylate synthase. Cancer 107(7):1589-1596

    Article  PubMed  CAS  Google Scholar 

  33. Ardizzoni A, Boni L, Tiseo M et al (2007) Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. J Natl Cancer Inst 99(11):847-857

    Article  PubMed  CAS  Google Scholar 

  34. D’Addario G, Pintilie M, Leighl NB, Feld R, Cerny T, Shepherd FA (2005) Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a meta-analysis of the published literature. J Clin Oncol 23(13):2926-2936

    Article  PubMed  Google Scholar 

  35. Smith IE, O’Brien ME, Talbot DC et al (2001) Duration of chemotherapy in advanced non-small-cell lung cancer: a randomized trial of three versus six courses of mitomycin, vinblastine, and cisplatin. J Clin Oncol 19(5):1336-1343

    PubMed  CAS  Google Scholar 

  36. von Plessen C, Bergman B, Andresen O et al (2006) Palliative chemotherapy beyond three courses conveys no survival or consistent quality-of-life benefits in advanced non-small-cell lung cancer. Br J Cancer 95(8):966-973

    Article  Google Scholar 

  37. Socinski MA, Schell MJ, Peterman A et al (2002) Phase III trial comparing a defined duration of therapy versus continuous therapy followed by second-line therapy in advanced-stage IIIB/IV non-small-cell lung cancer. J Clin Oncol 20(5):1335-1343

    Article  PubMed  CAS  Google Scholar 

  38. Belani CP, Barstis J, Perry MC et al (2003) Multicenter, randomized trial for stage IIIB or IV non-small-cell lung cancer using weekly paclitaxel and carboplatin followed by maintenance weekly paclitaxel or observation. J Clin Oncol 21(15):2933-2939

    Article  PubMed  CAS  Google Scholar 

  39. Brodowicz T, Krzakowski M, Zwitter M et al (2006) Cisplatin and gemcitabine first-line chemotherapy followed by maintenance gemcitabine or best supportive care in advanced non-small cell lung cancer: a phase III trial. Lung Cancer 52(2):155-163

    Article  PubMed  Google Scholar 

  40. Pfister DG, Johnson DH, Azzoli CG et al (2004) American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol 22(2):330-353

    Article  PubMed  Google Scholar 

  41. Fidias P, Dakhil S, Lyss A, et al (2007) Phase III study of immediate versus delayed docetaxel after induction therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer: updated report with survival. J Clin Oncol, 2007 ASCO Annual Meeting Proceedings Part I 25(18S) (Abstract no. LBA7516)

    Google Scholar 

  42. Soon Y, Stockler MR, Boyer M, Askie L (2008) Duration of chemotherapy for advanced non-small cell lung cancer: an updated systematic review and meta-analysis. J Clin Oncol 26 (Abstract no. 8013)

    Google Scholar 

  43. Johnson DH, Fehrenbacher L, Novotny WF et al (2004) Randomized phase II trial comparing bevacizumab plus carboplatin and paclitaxel with carboplatin and paclitaxel alone in previously untreated locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 22(11):2184-2191

    Article  PubMed  CAS  Google Scholar 

  44. Manegold C, Pawel Jv, Zatloukal P, et al (2007) Randomised, double-blind multicentre phase III study of bevacizumab in combination with cisplatin and gemcitabine in chemotherapy-naïve patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC): BO17704. J Clin Oncol, 2007 ASCO Annual Meeting Proceedings Part I 25(18S) (Abstract no. LBA7514)

    Google Scholar 

  45. Manegold C, Pawel Jv, Zatloukal P, et al (2008) BO17704 (AVAIL): a phase III randomised study of first-line bevacizumab combined with cisplatin/gemcitabine (CG) in patients (pts) with advanced or recurrent non-squamous, non-small cell lung cancer (NSCLC). Ann Oncol 19(suppl 8):viii1

    Google Scholar 

  46. Ciardiello F, Tortora G (2008) EGFR antagonists in cancer treatment. N Engl J Med 358(11):1160-1174

    Article  PubMed  CAS  Google Scholar 

  47. Giaccone G, Herbst RS, Manegold C et al (2004) Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 1. J Clin Oncol 22(5):777-784

    Article  PubMed  CAS  Google Scholar 

  48. Herbst RS, Giaccone G, Schiller JH et al (2004) Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase III trial-INTACT 2. J Clin Oncol 22(5):785-794

    Article  PubMed  CAS  Google Scholar 

  49. Herbst RS, Prager D, Hermann R et al (2005) 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 23(25):5892-5899

    Article  PubMed  CAS  Google Scholar 

  50. Gatzemeier U, Pluzanska A, Szczesna A et al (2007) Phase III study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial. J Clin Oncol 25(12):1545-1552

    Article  PubMed  CAS  Google Scholar 

  51. Stewart DJ (2008) Gefitinib maintenance in stage III non-small-cell lung cancer. J Clin Oncol 26(29):4849-4850; author reply 50-51

    Article  PubMed  Google Scholar 

  52. Mok T, Wu Y-L, Thongprasert S, et al (2008) Phase III randomised, open-label, first-line study of gefitinib (G) vs carboplatin/paclitaxel (C/P) in clinically selected patients (pts) with advanced non-small cell lung cancer (NSCLC) (IPASS). Ann Oncol 19(suppl 8):viii1

    Google Scholar 

  53. Butts CA, Bodkin D, Middleman EL et al (2007) Randomized phase II study of gemcitabine plus cisplatin or carboplatin [corrected], with or without cetuximab, as first-line therapy for patients with advanced or metastatic non small-cell lung cancer. J Clin Oncol 25(36):5777-5784

    Article  PubMed  CAS  Google Scholar 

  54. Lynch TJ, Patel T, Dreisbach L, et al (2007) A randomized multicenter phase III study of cetuximab (Erbitux®) in combination with Taxane/Carboplatin versus Taxane/Carboplatin alone as first-line treatment for patients with advanced/metastatic non-small cell lung cancer (NSCLC). J Thor Oncol 2(8 Suppl 4):S340

    Article  Google Scholar 

  55. Pirker R, Szczesna A, Pawel Jv, et al (2007) 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 (Abstract no. 3)

    Google Scholar 

  56. Havlik RJ, Yancik R, Long S, Ries L, Edwards B (1994) The National Institute on Aging and the National Cancer Institute SEER collaborative study on comorbidity and early diagnosis of cancer in the elderly. Cancer 74(7 Suppl):2101-2106

    Article  PubMed  CAS  Google Scholar 

  57. Lewis JH, Kilgore ML, Goldman DP et al (2003) Participation of patients 65 years of age or older in cancer clinical trials. J Clin Oncol 21(7):1383-1389

    Article  PubMed  Google Scholar 

  58. Langer CJ, Manola J, Bernardo P et al (2002) 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 94(3):173-181

    Article  PubMed  Google Scholar 

  59. Rocha Lima CM, Herndon JE, 2nd, Kosty M, Clamon G, Green MR (2002) Therapy choices among older patients with lung carcinoma: an evaluation of two trials of the Cancer and Leukemia Group B. Cancer 94(1):181-187

    Article  PubMed  Google Scholar 

  60. Belani CP, Fossella F (2005) Elderly subgroup analysis of a randomized phase III study of docetaxel plus platinum combinations versus vinorelbine plus cisplatin for first-line treatment of advanced nonsmall cell lung carcinoma (TAX 326). Cancer 104(12):2766-2774

    Article  PubMed  CAS  Google Scholar 

  61. Hensing TA, Peterman AH, Schell MJ, Lee JH, Socinski MA (2003) 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 98(4):779-788

    Article  PubMed  CAS  Google Scholar 

  62. Gridelli C, Perrone F, Gallo C et al (2003) 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 95(5):362-372

    Article  PubMed  CAS  Google Scholar 

  63. Frasci G, Lorusso V, Panza N et al (2000) Gemcitabine plus vinorelbine versus vinorelbine alone in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 18(13):2529-2536

    PubMed  CAS  Google Scholar 

  64. Stanley KE (1980) Prognostic factors for survival in patients with inoperable lung cancer. J Natl Cancer Inst 65(1):25-32

    PubMed  CAS  Google Scholar 

  65. Sweeney CJ, Zhu J, Sandler AB et al (2001) Outcome of patients with a performance status of 2 in Eastern Cooperative Oncology Group Study E1594: a Phase II trial in patients with metastatic nonsmall cell lung carcinoma. Cancer 92(10):2639-2647

    Article  PubMed  CAS  Google Scholar 

  66. Langer C, Li S, Schiller J, Tester W, Rapoport BL, Johnson DH (2007) Randomized phase II trial of paclitaxel plus carboplatin or gemcitabine plus cisplatin in Eastern Cooperative Oncology Group performance status 2 non-small-cell lung cancer patients: ECOG 1599. J Clin Oncol 25(4):418-423

    Article  PubMed  CAS  Google Scholar 

  67. Scagliotti GV, De Marinis F, Rinaldi M et al (2002) Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer. J Clin Oncol 20(21):4285-4291

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd. Unit 432, Houston, TX, 77030, USA

    William N. William Jr. & David J. Stewart

Authors
  1. William N. William Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David J. Stewart
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to William N. William Jr. .

Editor information

Editors and Affiliations

  1. M. D. Anderson Cancer Center, University of Texas, Holcombe Blvd. 1515, Houston, 77030, U.S.A.

    David J. Stewart

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Humana Press, a part of Springer Science+Business Media, LLC

About this chapter

Cite this chapter

William, W.N., Stewart, D.J. (2010). Management of Advanced Non-small Cell Lung Cancer: Front Line Treatment. In: Stewart, D. (eds) Lung Cancer. Current Clinical Oncology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-524-8_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-60761-524-8_8

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60761-523-1

  • Online ISBN: 978-1-60761-524-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation