Clinical and Translational Oncology

, Volume 10, Issue 9, pp 560–571

Adjuvant chemotherapy for early-stage non-small-cell lung cancer. Single-centre experience and literature review

  • Ana Belén Custodio Carretero
  • José Ángel García Sáenz
  • José Luis González Larriba
  • Jana Bobokova
  • Antonio Calles Blanco
  • Florentino Hernando Trancho
  • Beatriz García Paredes
  • Laura Rodríguez Lajusticia
  • Eduardo Díaz-Rubio García
Research Articles



In recent years platinum-based chemotherapy has become the standard of care for patients with good performance status after complete resection in stages IB-IIIA non-small-cell lung cancer (NSCLC), although the benefit is mainly in stages II and IIIA.

Patients and methods

In a retrospective trial we evaluate the clinical efficacy and toxicity profile of a platinum-and taxanes-based adjuvant chemotherapy in completely resected IB-IIIA NSCLC. The primary end point was relapse-free survival (RFS); principal secondary end points were overall survival (OS) and safety of the regimen. Potential predictive factors of efficacy and clinical patterns of relapse were also analysed.


From January 2003 to December 2006, 41 patients met the inclusion criteria and were evaluable. Median age at diagnosis was 68.1 years (CI 95% 54–72; range 45–78). Most patients were males (87.7%) and had an Eastern Cooperative Oncology Group performance status score (PS) of 0–1 (87.8%), and 53.6% had adenocarcinomas. Pathological stages were as follow: 48.7% stage IB, 24.3% stage II and 26.8% stage IIIA. 75.6% of patients underwent a lobectomy and mediastinal lymphadenectomy and were treated with a combination of carboplatin AUC6 and paclitaxel 200 mg/m2 (85.36%) for 3 or 4 cycles. With a median follow-up of 18.2 months (range 5.1–46.5), 26 patients (63%) were free of disease and 32 of them were alive (78%). Median RFS was 12.1 months (CI 95% 9.8–14.9) and median OS had not been reached at the time of analysis. Patients with PS ≤1 at diagnosis had a higher RFS [p=0.051 (CI 95% 0.90–0.96)]. Toxicity was generally mild and haematologic events were the most frequent. Non-haematologic toxic effects of chemotherapy were asthenia/anorexia (12.2%), nausea/vomiting (12.2%) and peripheral neuropathy (17%), but severe toxic effects (grade 3 or greater) were uncommon (<10%). We did not observe treatment-related deaths.


Platinum-taxane-based adjuvant chemotherapy in IB-IIIA NSCLC following complete resection is feasible, well tolerated and can be delivered in most patients in the adjuvant setting. Ongoing molecular studies may have value in determining which patients will benefit from adjuvant chemotherapy.


Non-small-cell lung cancer Surgical stage Adjuvant chemotherapy Platinum Taxanes 


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  1. 1.
    Jemal A, Siegel R, Ward E et al (2007) Cancer statistics, 2007. CA Cancer J Clin 57:43–66PubMedCrossRefGoogle Scholar
  2. 2.
    Parkin DM, Bray F, Ferlay J, Pisani P (2001) Estimating the world cancer burden: Globoscan 2000. Int J Cancer 94:153–156PubMedCrossRefGoogle Scholar
  3. 3.
    Pisani P, Parkin DM, Ferlay J (1993) Estimates of the worldwide mortality from eighteen major cancers in 1985. Implications for prevention and projections of future burden. Int J Cancer 55:891–903PubMedCrossRefGoogle Scholar
  4. 4.
    Brambilla E, Travis WD, Colby TV et al (2001) The new World Health Organization classification of lung tumours. Eur Respir J 18:1059–1068PubMedCrossRefGoogle Scholar
  5. 5.
    Mountain CF (1997) Revisions in the International System for Staging Lung Cancer. Chest 111:1710–1717PubMedCrossRefGoogle Scholar
  6. 6.
    Manser R, Wright G, Hart D et al (2005) Surgery for early stage non-small cell lung cancer. Cochrane Database Syst Rev Jan 25;1:CD 004699Google Scholar
  7. 7.
    Wright G, Manser RL, Byrnes G et al (2006) Surgery for non-small cell lung cancer: systematic review and meta-analysis of randomised controlled trials. Thorax 61:597–603PubMedCrossRefGoogle Scholar
  8. 8.
    Van Rens MT, de la Rivière AB, Elbers HR, van Den Bosch JM (2000) Prognostic assessment of 2,361 patients who underwent pulmonary resection for non-small cell lung cancer, stage I, II, and IIIA. Chest 117:374–379PubMedCrossRefGoogle Scholar
  9. 9.
    Fry WA, Phillips JL, Menck HR (1999) Ten-year survey of lung cancer treatment and survival in hospitals in the United States: a national cancer data base report. Cancer 86:1867–1876PubMedCrossRefGoogle Scholar
  10. 10.
    Early Breast Cancer Trialists’ Collaborative Group (1992) Systemic treatment of early breast cancer by hormonal, cytotoxic or immune therapy: 133 randomised trials involving 31000 recurrences and 24000 deaths among 75000 women. Lancet 339:1–15, 71–85Google Scholar
  11. 11.
    Trimbos JB, Parmar M, Vergote I et al (2003) International Collaborative Ovarian Neoplasm trial 1 and adjuvant chemotherapy in Ovarian Neoplasm trial: two parallel randomized phase III trials of adjuvant chemotherapy in patients with early-stage ovarian carcinoma. J Natl Cancer Inst 95: 105–112PubMedGoogle Scholar
  12. 12.
    André T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343–2351PubMedCrossRefGoogle Scholar
  13. 13.
    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 311:899–909Google Scholar
  14. 14.
    Keller SM, Adak S, Wagner H et al (2000) A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small cell lung cancer. Eastern Cooperative Oncology Group. N Engl J Med 343:1217–1222PubMedCrossRefGoogle Scholar
  15. 15.
    Scagliotti GV, Fossati R, Torri V et al (2003) Randomized study of adjuvant chemotherapy for completely resected stage I, II or IIIA non-small cell lung cancer. J Natl Cancer Inst 95:1453–1461PubMedGoogle Scholar
  16. 16.
    Waller D, Peake MD, Stephens RJ et al (2004) Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial. Eur J Cardiothorac Surg 26:173–182PubMedCrossRefGoogle Scholar
  17. 17.
    The 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 350:351–360CrossRefGoogle Scholar
  18. 18.
    Winton T, Livingston R, Johnson D et al (2005) Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 352:2589–2597PubMedCrossRefGoogle Scholar
  19. 19.
    Douillard JY, Rosell R, de Lena M et al (2006) 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 7:719–727PubMedCrossRefGoogle Scholar
  20. 20.
    Pignon JP, Tribodet H, Scagliotti GV et al (2006) Lung Adjuvant Cisplatin Evaluation(LACE): a pooled analysis of 5 randomized trials including 4584 patients. J Clin Oncol 24:366S [Abstract No 7008 2006 ASCO Annual Meeting]Google Scholar
  21. 21.
    Wada H, Hitomi S, Teramatsu T (1996) Adjuvant chemotherapy after complete resection in non-small-cell lung cancer. West Japan Study Group for Lung Cancer Surgery. J Clin Oncol 14:1048–1054PubMedGoogle Scholar
  22. 22.
    Endo C, Saito Y, Iwanami H et al (2003) A randomized trial of postoperative UFT therapy in pathological stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery. Lung Cancer 40:181–186PubMedCrossRefGoogle Scholar
  23. 23.
    Nakawava M, Tanaka F, Tsubota N et al; West Japan Study Group for Lung Cancer Surgery (2005) A randomized phase III trial f adjuvant chemotherapy with UFT for completely resected pathological stage I non-small-cell lung cancer: the West Japan Study Group for Lung Cancer Surgery( WJSG)-the 4th study. Ann Oncol 16:75–80CrossRefGoogle Scholar
  24. 24.
    Nakagawa K, Tada H, Akashi A et al (2006) Randomised study of adjuvant chemotherapy for completely resected p-stage I-IIIA non-small cell lung cancer. Br J Cancer 95:817–821PubMedCrossRefGoogle Scholar
  25. 25.
    Kato H, Ichinose Y, Ohta M et al (2004) A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med 350:1713–1721PubMedCrossRefGoogle Scholar
  26. 26.
    Stewart LA, Burdett S, Tierney JF et al (2007) Surgery and adjuvant chemotherapy (CT) compared to surgery alone in non-small cell lung cancer (NSCLC): a meta-analysis using individual patient data (IPD) from randomized clinical trials (RCT). J Clin Oncol 25 [Abstract No 7552 2007 ASCO Annual Meeting]Google Scholar
  27. 27.
    Strauss GM, Herndon JE, Maddaus MA et al (2004) Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell lung cancer (NSCLC): report of Cancer and Leukemia Group B (CALGB) protocol 9633. J Clin Oncol 22:7019Google Scholar
  28. 28.
    Strauss GM, Herndon JE, Maddaus MA et al (2006) Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): update of cancer and leukemia Group B protocol 9633. J Clin Oncol 24 [Abstract-No 7007 2006 ASCO Annual Meeting]Google Scholar
  29. 29.
    Azzoli CG, Krug LM, Miller VA et al (2007) A phase II tolerability study of cisplatin plus docetaxel as adjuvant chemotherapy for resected non-small cell lung cancer. J Thorac Oncol 2: 638–644PubMedCrossRefGoogle Scholar
  30. 30.
    Feigenberg SJ, Hanlon AL, Langer C et al (2007) A phase II study of concurrent carboplatin and paclitaxel and thoracic radiotherapy for completely resected stage II and IIIA non-small cell lung cancer. J Thorac Oncol 2:287–292PubMedCrossRefGoogle Scholar
  31. 31.
    Kreuter M, Vansteenkiste J, Griesinger F et al (2007) Trial on refinement of early stage non-small cell lung cancer. Adjuvant chemotherapy with pemetrexed and cisplatin versus vinorelbine and cisplatin: the TREAT protocol. BMC Cancer 7:77PubMedCrossRefGoogle Scholar
  32. 32.
    Bradley JD, Paulus R, Graham MV et al (2005) Phase II of postoperative adjuvant paclitaxel/carboplatin and thoracic radiotherapy in resected stage II and IIIA non-small-cell lung cancer: promising long-term results of the Radiation Therapy Oncology Group-RTOG 9705. J Clin Oncol 23:3480–3487PubMedCrossRefGoogle Scholar
  33. 33.
    Greco FA, Burris HA 3rd, Gray JR et al (2001) Paclitaxel and carboplatin adjuvant chemotherapy alone or with radiotherapy for resected nonsmall cell lung carcinoma: a feasibility study of the Minnie Pearl Cancer Research Network. Cancer 92:2142–2147PubMedCrossRefGoogle Scholar
  34. 34.
    Kawamura M, Eguchi K, Izumi Y et al (2007) Phase II trial of gemcitabine and docetaxel in patients with completely resected stage IIA-IIIA non-small-cell lung cancer. Cancer Chemother Pharmacol 60:495–501PubMedCrossRefGoogle Scholar
  35. 35.
    Hamada C, Tanaka F, Ohta M et al (2005) Meta-analysis of postoperative adjuvant chemotherapy with tegafur-uracil in non-small-cell lung cancer. J Clin Oncol 23:4999–5006PubMedCrossRefGoogle Scholar
  36. 36.
    Pisters KM, Evans WK, Azzoli CG et al (2007) Cancer Care Ontario and American Society of Clinical Oncology adjuvant chemotherapy and adjuvant radiation therapy for stages I–IIIA resectable non small-cell lung cancer guideline. J Clin Oncol 25:5506PubMedCrossRefGoogle Scholar
  37. 37.
    National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Available at
  38. 38.
    Feng QF, Wang M, Wang LJ et al (2000) A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial. Int J Radiat Oncol Biol Phys 47:925–929PubMedGoogle Scholar
  39. 39.
    Dautzenberg B, Arriagada R, Chammard AB et al (1999) A controlled study of postoperative radiotherapy for patients with completely resected non-small cell lung carcinoma. Groupe d’Etude et de Traitement des Cancers Bronchiques. Cancer 86:265–273PubMedCrossRefGoogle Scholar
  40. 40.
    Stephens RJ, Irling DJ, Bleehen NM et al (1996) The role of post-operative radiotherapy in non-small-cell lung cancer: a multicentre randomised trial in patients with pathologically staged T1-2, N1-2, M0 disease. Medical Research Council Lung Cancer Working Party. Br J Cancer 74:632–639PubMedGoogle Scholar
  41. 41.
    PORT Meta-analysis Trialists Group (1998) Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patients data from nine randomised controlled trials. Lancet 352:257–263CrossRefGoogle Scholar
  42. 42.
    Trodella L, Granone P, Valente S et al (2002) Adjuvant radiotherapy in non-small cell lung cancer with pathological stage I: definitive results of a phase III randomized trial. Radiother Oncol 62:11–19PubMedCrossRefGoogle Scholar
  43. 43.
    Hoang T, Xu R, Schiller JH et al (2005) Clinical model to predict survival in chemonaïve patients with advanced non-small-cell lung cancer treated with third-generation chemotherapy regimens based on eastern cooperative oncology group data. J Clin Oncol 23:175–183PubMedCrossRefGoogle Scholar
  44. 44.
    The Lung Cancer Study Group (1987) Postoperative T1N0 non-small cell lung cancer. Squamous versus nonsquamous recurrences. J Thorac Cardiovasc Surg 94:349–354Google Scholar
  45. 45.
    Pairolero PC, Williams DE, Bergstralh EJ et al (1984) Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrence disease. Ann Thorac Surg 38:331–338PubMedCrossRefGoogle Scholar
  46. 46.
    Mountain CF (1995) New prognostic factors in lung cancer. Biologic prophets of cancer cell aggression. Chest 108:246–254PubMedCrossRefGoogle Scholar
  47. 47.
    Potti A, Mukherjee S, Petersen R et al (2006) A genomic strategy to refine prognosis in earlystage non-small-cell lung cancer. N Engl J Med 355:570–580PubMedCrossRefGoogle Scholar
  48. 48.
    Chen H-Y, Yu S-L, Chen CH et al (2007) A five-gene signature and clinical outcome in non-small-cell lung cancer. N Engl J Med 356:11–20PubMedCrossRefGoogle Scholar
  49. 49.
    Altaha R, Liang X, Yu JJ, Reed E (2004) Excision repair cross complementing-group 1: gene expression and platinum resistance. Int J Mol Med 14: 959–970PubMedGoogle Scholar
  50. 50.
    Lord RV, Brabender J, Gandara D et al (2002) Low ERCC1 expression correlates with prolonged survival after cisplatin plus gemcitabine chemotherapy in non-small cell lung cancer. Clin Cancer Res 8:2286–2291PubMedGoogle Scholar
  51. 51.
    Olaussen KA, Dunant A, Fouret P et al (2006) DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 355:983–991PubMedCrossRefGoogle Scholar
  52. 52.
    Bepler G, Sharma S, Cantor A et al (2004) RMM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer. J Clin Oncol 22: 1878–1885PubMedCrossRefGoogle Scholar
  53. 53.
    Zheng Z, Chen T, Li X et al (2007) DNA synthesis and repair genes RMM1 and ERCC1 in lung cancer. N Engl J Med 356:800–808PubMedCrossRefGoogle Scholar
  54. 54.
    Rosell R, Jassem M, Skrzypski M et al (2007) Increased BRCA1 mRNA: an independent prognostic variable in completely resected chemo-naïve non-small cell lung cancer (NSCLC) patients (p). [Abstract No. 7551 2007 ASCO Annual Meeting]Google Scholar

Copyright information

© Feseo 2008

Authors and Affiliations

  • Ana Belén Custodio Carretero
    • 1
  • José Ángel García Sáenz
    • 1
  • José Luis González Larriba
    • 1
  • Jana Bobokova
    • 1
  • Antonio Calles Blanco
    • 1
  • Florentino Hernando Trancho
    • 2
  • Beatriz García Paredes
    • 1
  • Laura Rodríguez Lajusticia
    • 1
  • Eduardo Díaz-Rubio García
    • 1
  1. 1.Oncology DepartmentHospital Universitario Clínico San CarlosMadridSpain
  2. 2.Thoracic Surgery DepartmentHospital Universitario Clínico San CarlosMadridSpain

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