Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Chemoradiation paradigm for the treatment of lung cancer

Nature Clinical Practice Oncology volume 3, pages 188–199 (2006)Cite this article

Abstract

For the treatment of locoregional advanced stage III non-small-cell lung cancer, when chemotherapy is added sequentially to radiotherapy it acts systemically and is aimed at reducing distant metastases. Concurrent chemotherapy and radiation, however, is intended to enhance the locoregional efficacy of this modality. Combined effects of these modalities are based on their different toxicity profiles, leading to a reduced toxicity : efficacy ratio of the combination. Controlled trials investigating this additive approach indicate that concurrent application of chemotherapy and radiotherapy results in a small but significant benefit for locoregional control, which translates into a small but measurable survival benefit. This benefit is most evident when looking at 3-year or 5-year overall survival rates, when it is of clinical significance. The use of single-agent cisplatin has already demonstrated major radiosensitizing effects whereas the radiosensitizing properties of concurrent application of the single-agent carboplatin have not been observed in controlled trials. Newer drugs such as vinorelbine, the taxanes and gemcitabine might enhance this effect, although no improvement has been observed in randomized controlled trials comparing such regimens with single-agent cisplatin. New 'targeted' agents might synergize with ionizing irradiation and provide an interesting rationale concerning combined modality therapy, but this hypothesis awaits prospective clinical evidence from randomized controlled trials.

Key Points

  • Based on data from multicenter phase III trials, combining platinum-based chemotherapy and radiotherapy to treat patients with locally advanced and inoperable NSCLC improves median and long-term survival

  • Sequential administration of chemotherapy prior to radiotherapy compared with radiotherapy alone improves median as well as long-term survival by increasing systemic control

  • Combining concurrent cisplatin-based or platinum-based chemotherapy to radiation increases median survival and long-term survival by improvement of local control

  • Data from phase III randomized trials indicate that a cisplatin-based combination chemoradiotherapy regimen is the preferable choice when using a concurrent chemoradiation protocol

  • Combining chemotherapy and radiotherapy increases both hematological and nonhematological toxicities, but with adequate supportive measures treatment compliance is generally good

  • Future prospective randomized studies should evaluate newer chemotherapeutic and molecular targeted agents, as well as innovative, more intensive and conformal radiation schedules within these multimodality protocols

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Jemal A et al. (2005) Cancer Statistics, 2005. CA Cancer J Clin 55: 10–30

    Article  PubMed  Google Scholar 

  2. Travis WD et al. (2004) Pathology and Genetics: Tumours of the Lung, Pleura, Thymus and Heart. Lyon: IARC.

    Google Scholar 

  3. Mountain CF (1997) Revisions in the International System for Staging Lung Cancer. Chest 111: 1711–1717

    Google Scholar 

  4. Ginsberg RJ et al. (2001) Non-small-cell lung cancer. In Cancer: Principles and Practice of Oncology, edn 6, 925–983 (Eds DeVita VT Jr et al.) Philadelphia: Lippincott

    Google Scholar 

  5. Eberhardt W et al. (2003) Induction therapy before surgery in stage III non-small-cell lung cancer: IASLC Brugges Consensus. Lung Cancer 42 (Suppl 1): S9–S14

    Article  PubMed  Google Scholar 

  6. Farray D et al. (2005) Multimodality therapy for stage III non-small-cell lung cancer. J Clin Oncol 23: 3257–3269

    Article  CAS  PubMed  Google Scholar 

  7. Perez CA et al. (1987) Long-term observations of the patterns of failure in patients with unresectable non-oat cell carcinoma of the lung treated with definitive radiotherapy. Cancer 59: 1874–1881

    Article  CAS  PubMed  Google Scholar 

  8. Albain KS et al. (1995) Concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery for stages IIIA (N2) and IIIB non-small-cell lung cancer: mature results of Southwest Oncology Group Phase II Study 8805. J Clin Oncol 13: 1880–1892

    Article  CAS  PubMed  Google Scholar 

  9. Eberhardt W et al. (1998) Preoperative chemotherapy followed by concurrent chemoradiation therapy based on hyperfractionated accelerated radiotherapy and definitive surgery in locally advanced non-small-cell lung cancer: mature results of a phase-II trial. J Clin Oncol 16: 622–634

    Article  CAS  PubMed  Google Scholar 

  10. Eberhardt WE et al. (2005) The role of surgery in stage IIIA non-small cell lung cancer. Hematol Oncol Clin North Am 19: 303–319

    Article  PubMed  Google Scholar 

  11. Stuschke M et al. (1999) Prophylactic cranial irradiation in locally advanced non–small-cell lung cancer after multimodality treatment: long-term follow-up and investigations of late neuro-psychologic effects. J Clin Oncol 17: 2700–2709

    Article  CAS  PubMed  Google Scholar 

  12. Dewey WC and Bedford JS (2004) Radiobiologic principles. In Textbook of Radiation Oncology, edn 2, 3–29 (Eds Leibel SA and Phillips TL) Philadelphia: Saunders

    Google Scholar 

  13. Weichselbaum RR et al. (1995) Cellular and molecular mechanisms of radioresistance. Cancer Treat Res 74: 131–140

    Article  CAS  PubMed  Google Scholar 

  14. Dische S and Saunders MI (1990) The rationale for continuous, hyperfractionated, accelerated radiotherapy (CHART). Int J Radiat Oncol Biol Phys 19: 1317–1320

    Article  CAS  PubMed  Google Scholar 

  15. Withers HR et al. (1988) The hazard of accelerated tumor clonogen repopulation during radiotherapy. Acta Oncol 27: 131–146

    Article  CAS  PubMed  Google Scholar 

  16. Milas L et al. (1995) Role of reoxygenation in induction of enhancement of tumor radioresponse by paclitaxel. Cancer Res 55: 3564–3568

    CAS  PubMed  Google Scholar 

  17. Chabner B (1993) The biological basis of cancer chemotherapy. Ann Intern Med 118: 633–637

    Article  CAS  PubMed  Google Scholar 

  18. Calabresi P and Chabner B (2001) Chemotherapy of neoplastic diseases. In Goodman and Gilman's The Pharmacological Basis of Therapeutics, edn 10, 1381–1459 (Eds Gilman A et al.) New York: McGraw-Hill

    Google Scholar 

  19. Zamble DB et al. (1996) Repair of cisplatin-DNA by the mammalian excision nuclease. Biochemistry 35: 10004–10013

    Article  CAS  PubMed  Google Scholar 

  20. Milas L et al. (1999) Combination of taxanes with radiation: preclinical studies. Semin Radiat Oncol 9: 12–26

    CAS  PubMed  Google Scholar 

  21. Milas L et al. (2001) Docetaxel and radiation in lung cancer: preclinical investigations. Adv Lung Cancer 3: 6–8

    Google Scholar 

  22. Milas L et al. (1999) Enhancement of tumor radioresponse in vivo by gemcitabine. Cancer Res 59: 107–114

    CAS  PubMed  Google Scholar 

  23. Edelstein et al. (1995) Potentiation of radiotherapy by Navelbine (NVB) in a human non-small cell lung cancer (NSCLC) line [abstract #611]. Proc Am Assoc Cancer Res 36

  24. Niero A et al. (1999) Paclitaxel and radiotherapy: sequence-dependent efficacy—a preclinical model. Clin Cancer Res 5: 2213–2222

    CAS  PubMed  Google Scholar 

  25. Steel GG et al. (1979) Exploitable mechanisms in combined radiotherapy–chemotherapy: the concept of additivity. Int J Radiat Oncol Biol Phys 5: 85–91

    Article  CAS  PubMed  Google Scholar 

  26. Tannock IF et al. (1996) Treatment of cancer with radiation and drugs. J Clin Oncol 52: 3156–3174

    Article  Google Scholar 

  27. Herscher LL et al. (1999) Principles of chemoradiation: theoretical and practical considerations. Oncology 13 (Suppl 5): S11–S22

    Google Scholar 

  28. Non-small Cell Lung Cancer Collaborative Group (1995) Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials. BMJ 311: 899–909

  29. International Adjuvant Lung Cancer Trial Collaborative Group (2004) Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 350: 351–360

  30. Vokes EE et al. (1997) Combined modality therapy of solid tumours. Lancet 349 (Suppl 2): SII4–SII6

    Article  PubMed  Google Scholar 

  31. Dillman RO et al. (1996) Improved survival of stage III non-small cell lung cancer: seven-year follow-up of Cancer and Leukemia Group B (CALGB) 8433 trial. J Natl Cancer Inst 88: 1210–1215

    Article  CAS  PubMed  Google Scholar 

  32. Le Chevalier T et al. (1992) Significant effect of adjuvant chemotherapy on survival in locally advanced non-small-cell lung carcinoma. J Natl Cancer Inst 84: 58

    Article  CAS  PubMed  Google Scholar 

  33. Arriagada R et al. (1997) Cisplatin-based chemoradiotherapy in patients with locally advanced non-small-cell lung cancer (NSCLC): late analysis of a French randomized trial [abstract #446]. Proc Am Soc Clin Oncol 16

  34. Sause WT et al. (2000) Final results of phase III trial in regionally advanced unresectable non-small cell lung cancer: Radiation Therapy Oncology Group, Eastern Cooperative Oncology Group, Southwest Oncology Group. Chest 117: 358–364

    Article  CAS  PubMed  Google Scholar 

  35. Brodin O et al. (1996) Comparison of induction chemotherapy before radiotherapy with radiotherapy only in patients with locally advanced squamous cell carcinoma of the lung. Eur J Cancer 32A: 1893–1900

    Article  CAS  PubMed  Google Scholar 

  36. Hotta K et al. (2004) Meta-analysis of randomized clinical trials comparing cisplatin to carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 22: 3852–3859

    Article  CAS  PubMed  Google Scholar 

  37. Trovo M et al. (1992) Radiotherapy versus radiotherapy enhanced by cisplatin in stage III non-small cell lung cancer. Int J Radiat Oncol Biol Phys 24: 11–15

    Article  CAS  PubMed  Google Scholar 

  38. Schaake-Koning C et al. (1992) Effects of concomitant cisplatin and radiotherapy on inoperable non-small-cell lung cancer. N Engl J Med 326: 524–530

    Article  CAS  PubMed  Google Scholar 

  39. Cakir S and Egehan I (2004) A randomised clinical trial of radiotherapy plus cisplatin versus radiotherapy alone in stage III non-small cell lung cancer. Lung Cancer 43: 309–316

    Article  PubMed  Google Scholar 

  40. Blanke C et al. (1995) Phase III trial of thoracic irradiation with or without cisplatin for locally advanced unresectable non-small cell lung cancer: a Hoosier Oncology Group Protocol. J Clin Oncol 13: 1425–1429

    Article  CAS  PubMed  Google Scholar 

  41. Clamon G et al. (1999) Radiosensitization with carboplatin for patients with unresectable stage III non-small-cell lung cancer: a phase III trial of the Cancer and Leukemia Group B and the Eastern Cooperative Oncology Group. J Clin Oncol 17: 4–11

    Article  CAS  PubMed  Google Scholar 

  42. Groen H et al. (2004) Continuously infused carboplatin used as radiosensitizer in locally unresectable non-small-cell lung cancer: a multicenter phase III study. Ann Oncol 15: 427–432

    Article  CAS  PubMed  Google Scholar 

  43. Vokes EE et al. (2002) Randomized phase II study of cisplatin with gemcitabine or paclitaxel or vinorelbine as induction chemotherapy followed by concomitant chemoradiotherapy for stage IIIB non-small-cell lung cancer: Cancer and Leukemia Group B study 9431. J Clin Oncol 20: 4191–4198

    Article  CAS  PubMed  Google Scholar 

  44. Furuse K et al. (1999) 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 17: 2692–2699

    Article  CAS  PubMed  Google Scholar 

  45. Curran W et al. (2003) Long-term benefit is observed in a phase III comparison of sequential vs concurrent chemo-radiation for patients with unresected stage III NSCLC: RTOG 9410 [abstract #621]. Proc Am Soc Clin Oncol 22

  46. Fournel P et al. (2005) Randomized phase III trial of sequential chemoradiotherapy compared with concurrent chemoradiotherapy in locally advanced non-small-cell lung cancer: Groupe Lyon-Saint-Etienne d'Oncologie Thoracique-Groupe Francais de Pneumo-Cancerologie NPC 95–01 Study. J Clin Oncol [doi: 10.1200/JCO.2005.03.070]

  47. Huber RM et al. (2003) Induction chemotherapy and following simultaneous radio/chemotherapy versus induction chemotherapy and radiotherapy alone in inoperable NSCLC (stage IIIA/IIIB) [abstract #622]. Proc Am Soc Clin Oncol 22

  48. Vokes EE et al. (2004) Induction chemotherapy followed by concomitant chemoradiotherapy (CT/XRT) versus CT/XRT alone for regionally advanced unresectable non-small cell lung cancer (NSCLC): initial analysis of a randomized phase III trial [abstract #7005]. J Clin Oncol 22 (Suppl)

  49. Albain KS et al. (2005) Phase III study of concurrent chemotherapy and radiotherapy (CT/RT) vs CT/RT followed by surgical resection for stage IIIA(pN2) non-small cell lung cancer (NSCLC): outcomes update of North American Intergroup 0139 (RTOG 9309). J Clin Oncol 23: 624S

    Article  Google Scholar 

  50. Ball D et al. (1999) A phase III study of accelerated or standard fraction radiotherapy with or without concurrent carboplatin in inoperable non-small-cell lung cancer: final report of an Australian multi-centre trial. Radiother Oncol 52: 129–136

    Article  CAS  PubMed  Google Scholar 

  51. Belani C et al. (2005) Phase-III study of the Eastern Cooperative Oncology Group: Induction chemotherapy followed by either standard thoracic radiotherapy or hyperfractionated accellerated radiotherapy for patients with unresectable stage IIIA and B non-small-cell lung cancer. J Clin Oncol 23: 3760–3767

    Article  CAS  PubMed  Google Scholar 

  52. Schild SE et al. (2002) Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in stage III non-small cell lung cancer. Int J Radiat Oncol Biol Phys 54: 370–378

    Article  PubMed  Google Scholar 

  53. Movsas B et al. (2005) Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: Radiation Therapy Oncology Group trial 98–01. J Clin Oncol 23: 2145–2154

    Article  CAS  PubMed  Google Scholar 

  54. Gandara D et al. (2003) Consolidation docetaxel after concurrent chemoradiotherapy in stage IIIB non-small-cell lung cancer: phase-II Southwest Oncology Group Study S9504. J Clin Oncol 21: 2004–2010

    Article  CAS  PubMed  Google Scholar 

  55. Kelly K et al. (2005) Low incidence of pneumonitis on SWOG 0023: a preliminary analysis of an ongoing phase III trial of concurrent chemoradiotherapy followed by consolidation docetaxel and Iressa/placebo maintenance in patients with inoperable stage III non-small cell lung cancer [abstract #7058]. J Clin Oncol 23

  56. Belani C et al. (2005) Combined chemoradiotherapy regimens of paclitaxel and carboplatin for locally advanced non-small-cell lung cancer: a randomized phase II locally advanced multi-modality protocol. J Clin Oncol [doi: 10.1200/JCO.2005.55.405]

  57. Rowell NP et al. (2005) Concurrent chemoradiotherapy in non-small-cell lung cancer. The Cochrane Database of Systematic Reviews, Issue 4, Art No CD002140

    Google Scholar 

  58. Bonner JA et al. (2004) Cetuximab prolongs survival in patients with locoregionally advanced squamous cell carcinoma of head and neck: a phase III study of high dose radiation therapy with or without cetuximab. 22: S5507

  59. Kim DW et al. (2004) Potential role for epidermal growth factor receptor inhibitors in combined-modality therapy for non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 59 (Suppl): S11–S20

    Article  CAS  Google Scholar 

  60. Raben D et al. (2004) Targeted therapies for non-small-cell lung cancer: biology, rationale, and preclinical results from a radiation oncology perspective. Int J Radiat Oncol Biol Phys 59 (Suppl): S27–S38

    Article  CAS  Google Scholar 

  61. Bradley J et al. (2005) Toxicity and outcome results of RTOG 9311: a phase I–II dose escalation study using three-dimensional conformal radiation therapy in patients with inoperable non-small cell lung cancinoma. Int J Radiat Oncol Biol Phys 61: 318–328

    Article  PubMed  Google Scholar 

  62. Socinski et al. (2004) Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase-I trial. J Clin Oncol 22: 4341–4350

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Outpatient Unit,

    Wilfried Eberhardt, Christoph Pöttgen & Martin Stuschke

  2. Senior Physician,

    Wilfried Eberhardt, Christoph Pöttgen & Martin Stuschke

  3. Director in the Department of Radiotherapy, West German Cancer Centre, Essen, Germany

    Wilfried Eberhardt, Christoph Pöttgen & Martin Stuschke

Authors
  1. Wilfried Eberhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christoph Pöttgen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Stuschke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wilfried Eberhardt.

Ethics declarations

Competing interests

Dr Wilfried Eberhardt has declared the following competing interests: honorary for talks, advisory board function and he has received clinical trials grant funding from Bristol-Myers Squibb, Pierre Fabre, Eli Lilly, Merck (Darmstadt). He holds no stocks nor has any other major financial interest in the above mentioned companies.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eberhardt, W., Pöttgen, C. & Stuschke, M. Chemoradiation paradigm for the treatment of lung cancer. Nat Rev Clin Oncol 3, 188–199 (2006). https://doi.org/10.1038/ncponc0461

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncponc0461

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing