Abstract
Lung cancer is the leading cause of cancer death among men and women in the US. Surgical resection is potentially curative; however, even after complete resection many patients experience systemic recurrence and subsequently die of their disease. As a means of reducing the chances of recurrence there has been significant interest in combining chemotherapy with surgical resection. Recently, several large phase III clinical trials have demonstrated a significant survival benefit with adjuvant or postoperative cisplatin-based chemotherapy. Use of preoperative or induction chemotherapy has also been an area of active investigation; however, the trials that have demonstrated a survival benefit were small in size, and there has not been widespread acceptance of this treatment approach. The trials of induction chemoradiotherapy have generally been performed in patients with locally advanced disease, frequently in patients with involvement of the level 2 mediastinal lymph nodes (N2). The results of the recent US Intergroup trial, 0139, which compared induction chemoradiotherapy followed by surgical resection versus nonsurgical therapy with chemoradiotherapy in patients with resectable stage IIIA-N2 disease, revealed equivalent overall survival between the two treatment approaches. The results of an unplanned subset analysis of patients who were treated with lobectomy in the surgical arm have generated significant interest and debate. When the strategy of induction therapy is used, pathological clearance of the mediastinal lymph nodes is a significant prognostic factor for overall survival. Current investigations are attempting to determine the optimal method of assessing this critical prognostic factor. The toxicity, efficacy and proper selection of patients for induction therapy, particularly induction chemoradiotherapy, will be assessed in ongoing and future clinical trials.
Similar content being viewed by others
References
Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2006. CA Cancer J Clin 2006; 56: 106–30
Govindan R, Page N, Morgensztern D, et al. Changing epidemiology of small-cell lung cancer in the United States over the last 30 years: analysis of the surveillance, epidemiologic, and end results database. J Clin Oncol 2006; 24 (28): 4539–44
Bulzebruck H, Bopp R, Drings P, et al. New aspects in the staging of lung cancer: prospective validation of the International Union Against Cancer TNM classification. Cancer 1992; 70: 1102–10
Yang P, Allen MS, Aubry MC, et al. Clinical features of 5,628 primary lung cancer patients: experience at Mayo Clinic from 1997 to 2003. Chest 2005; 128: 452–62
Rusch VW, Giroux DJ, Kraut MJ, et al. Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: initial results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). J Thorac Cardiovasc Surg 2001; 121: 472–83
Rendina EA, Venuta F, De Giacomo T, et al. Induction chemotherapy for T4 centrally located non-small cell lung cancer. J Thorac Cardiovasc Surg 1999; 117: 225–33
Albain KS, Rusch K, Crowley J, et al. Long term survival after concurrent cisplatin/etoposide plus chest radiotherapy followed by surgery in bulky, stages IIIA (N2) and IIIB non-small cell lung cancer: 6-year outcomes from Southwest Oncology Group Study 8805 [abstract no. 1801]. 35th Annual Meeting of the American Society of Clinical Oncology; 1999 May 15–18; Atlanta (GA). Pro Am Soc Clin Oncol 1999; 19: 467a
Pisters KM, Le Chevalier T. Adjuvant chemotherapy in completely resected non-small-cell lung cancer. J Clin Oncol 2005; 23: 3270–8
Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997; 111 (6): 1710–7
Non-Small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials. BMJ 1995; 311: 899–909
Douillard JY, Rosell R, Delena M, et al. ANITA: phase III adjuvant vinorelbine (N) and cisplatin (P) versus observation (OBS) in completely resected (stage I-III) non-small cell lung cancer (NSCLC) patients: final results after 70-month median follow-up. On behalf of the Adjuvant Navelbine International Trialist Association [abstract no. 7013]. 41st Annual Meeting of the American Society of Clinical Oncology; 2005 May 13–17; Orlando (FL). J Clin Oncol 2005; 23: 624s
Winton T, Livingston R, Johnson D, et al. Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med 2005; 352: 2589–97
Arriagada R, Bergman B, Dunant A, et al. Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med 2004; 350: 351–60
Randomized clinical trial of adjuvant chemotherapy with paclitaxel and carboplatin following resection in stage IB non-small cell lung cancer: report of cancer and leukemia Group B Protocol 9633 [abstract no. LBA7019]. 40th Annual Meeting of the American Society of Clinical Oncology; 2004 Jun 5–8; New Orleans (LA). J Clin Oncol 2004; 22: 621s
Strauss GM, Herndon II JE, Maddaus MA, et al. Adjuvant chemotherapy in stage IB non-small cell lung cancer (NSCLC): update of Cancer and Leukemia Group B (CALGB) protocol 9633 [abstract no. 7007]. 42nd Annual Meeting of the American Society of Clinical Oncology; 2006 Jun 2-6; Atlanta (GA). J Clin Oncol 2006; 24: 365s
Rosell R, Gomez-Codina J, Camps C, et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med 1994; 330: 153–8
Slebos RJ, Hruban RH, Dalesio O, et al. Relationship between K-ras oncogene activation and smoking in adenocarcinoma of the human lung. J Natl Cancer Inst 1991; 83: 1024–7
Graziano SL, Gamble GP, Newman NB, et al. Prognostic significance of K-ras codon 12 mutations in patients with resected stage I and II non-small-cell lung cancer. J Clin Oncol 1999; 17: 668–75
Slebos RJ, Kibbelaar RE, Dalesio O, et al. K-ras oncogene activation as a prognostic marker in adenocarcinoma of the lung. N Engl J Med 1990; 323 (9): 561–5
Schiller JH, Adak S, Feins RH, et al. Lack of prognostic significance of p53 and K-ras mutations in primary resected non-small-cell lung cancer on E4592: a laboratory ancillary study on an Eastern Cooperative Oncology Group prospective randomized trial of postoperative adjuvant therapy. J Clin Oncol 2006; 19: 448–57
Camps C, Sirera R, Bremnes R, et al. Is there a prognostic role of K-ras point mutations in the serum of patients with advanced non-small cell lung cancer? Lung Cancer 2005; 50: 339–46
Aviel-Ronen S, Blackhall FH, Shepherd FA, et al. K-ras mutations in non-small-cell lung carcinoma: a review. Clin Lung Cancer 2006; 8: 30–8
Pass H, Pogrebniak H, Steinberg S. Randomized trial of neoadjuvant therapy for lung cancer interim analysis. Ann Thorac Surg 1992; 53: 992–8
Roth JA, Atkinson EN, Fossella F, et al. Long-term follow-up of patients enrolled in a randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. Lung Cancer 1998; 21: 1–6
Roth JA, Fossella F, Komaki R, et al. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage IIIA non-small-cell lung cancer. J Natl Cancer Inst 1994; 86: 673–80
DePierre A, Milleron B, Moro-Sibilot D, et al. Preoperative chemotherapy followed by surgery compared with surgery in resectable stage I (except TINO), II, and IIIA non-small cell lung cancer. J Clin Oncol 2002; 20: 247–53
Nagai K, Tsuchiya R, Mori T, et al. A randomized trial comparing induction chemotherapy followed by surgery with surgery alone for patients with stage IIIA N2 non-small cell lung cancer (JCOG 9209). J Thorac Cardiovasc Surg 2003; 125: 254–60
Pisters K, Vallieres E, Bunn PA, et al. S9900: a phase III trial of surgery alone or preoperative (preop) paclitaxel/carboplatin (PC) chemotherapy in early stage non-small cell lung cancer (NSCLC): preliminary results [abstract no. 7012]. 41st Annual Meeting of the American Society of Clinical Oncology; 2005 May 13–17; Orlando (FL). J Clin Oncol 2005: 23: 624s
Mattson KV, Abratt RP, ten Velde G, et al. Docetaxel as neoadjuvant therapy for radically treatable stage III non-smallcell lung cancer: a multinational randomised phase III study. Ann Oncol 2003; 14 (1): 116–22
Pisters K, Ginsberg R, Giroux DJ, et al. Bimodality Lung Oncology Team (BLOT) trial of induction paclitaxel/carboplatin in early stage non-small cell lung cancer (NSCLC): long term follow-up of a phase II trial [abstract 2544]. 39th Annual Meeting of the American Society of Clinical Oncology; 2003 May 31–Jun 3; Chicago (IL). Proc Am Soc Clin Oncol 2003; 22: 633
Scagliotti G. Preliminary results of the CHEST: a phase III study of surgery alone or surgery plus preoperative gemcitabine-cisplatin in clinical early stages non-small cell lung cancer (NSCLC) [abstract no. LBA7023]. 41st Annual Meeting of the American Society of Clinical Oncology; 2005 May 13–17; Orlando (FL). J Clin Oncol 2005; 23: 626s
van Meerbeeck JP, Kramer G, van Schil PE, et al. A randomized trial of radical surgery (S) versus thoracic radiotherapy (TRT) in patients (pts) with stage IIIA-N2 non-small cell lung cancer (NSCLC) after response to induction chemotherapy (ICT) (EORTC 08941) [abstract no. LBA7015]. 41st Annual Meeting of the American Society of Clinical Oncology; 2005 May 13–17; Orlando (FL). J Clin Oncol 2005; 23: 624s
Albain KS, Swann RS, Rusch VR, et al. 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) [abstract no. 7014]. 41st Annual Meeting of the American Society of Clinical Oncology; 2005 May 13–17; Orlando (FL). J Clin Oncol 2005; 23: 624s
Johnstone DW, Byhardt RW, Ettinger D, et al. Phase III study comparing chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with non-small-cell lung cancer with spread to mediastinal lymph nodes (N2); final report of RTOG 89-01. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 2002; 54: 365–9
Shepherd FA, Johnston MR, Payne D, et al. Randomized study of chemotherapy and surgery versus radiotherapy for stage IIIA non-small-cell lung cancer: a National Cancer Institute of Canada Clinical Trials Group Study. Br J Cancer 1998; 78: 683–5
Andre F, Grunenwald D, Pignon JP, et al. Survival of patients with resected N2 non-small-cell lung cancer: evidence for a subclassification and implications. J Clin Oncol 2000; 18: 2981–9
Albain K, Rusch V, Crowley J, et al. Long-term survival after concurrent cisplatin/etoposide (PE) plus chest radiotherapy (RT) followed by surgery in bulky, stage IIIA (N2) and IIIB non-small cell lung cancer (NSCLC): 6-year outcomes from Southwest Oncology Group Study 8805 [abstract no. 1801]. 35th Annual Meeting of the American Society of Clinical Oncology; 1999 May 15–18; Atlanta (GA). Proc Am Soc Clin Oncol 1999; 18: 467a
Betticher DC, Hsu Schmitz SF, Totsch M, et al. Mediastinal lymph node clearance after docetaxel-cisplatin neoadjuvant chemotherapy is prognostic of survival in patients with stage IIIA pN2 non-small-cell lung cancer: a multicenter phase II trial. J Clin Oncol 2003; 21: 1752–9
Albain K, Scott C, Rusch V, et al. Phase III comparison of concurrent chemotherapy plus radiotherapy (CT/RT) and CT/RT followed by surgical resection for stage IIIA(pN2) non-small cell lung cancer (NSCLC): initial results from Intergroup trial 0139 (RTOG 93-09) [abstract no. 2497]. 39th Annual Meeting of the American Society of Clinical Oncology; 2003 May 31–Jun 3; Chicago (IL). Proc Am Soc Clin Oncol 2003; 22: 621
Bueno R, Richards WG, Swanson SJ, et al. Nodal stage after induction therapy for stage IIIA lung cancer determines patient survival. Ann Thorac Surg 2000; 70: 1826–31
Voltolini L, Luzzi L, Ghiribelli C, et al. Results of induction chemotherapy followed by surgical resection in patients with stage IIIA (N2) non-small cell lung cancer: the importance of the nodal down-staging after chemotherapy. Eur J Cardiothorac Surg 2001; 20: 1106–12
Detterbeck F, Ma S. Induction therapy and surgery for stage I–IIIA,B non-small lung cancer. In: Detterbeck F, Socinski M, Rivera M, et al., editors. Diagnosis and treatment of lung cancer. Philadelphia (PA): W.B. Saunders 2001: 267–82
Detterbeck FC, Socinski MA. Induction therapy and surgery for I–IIIA,B non-small cell lung cancer. In: Detterbeck FC, Socinski MA, Rivera MC, et al., editors. Diagnosis and treatment of lung cancer: an evidence-based guide for the practising clinician. Philadelphia (PA): W.B. Saunders Company, 2001: 267–82
Van Schil P, van der Schoot J, Poniewierski J, et al. Remediastinoscopy after neoadjuvant therapy for non-small cell lung cancer. Lung Cancer 2002; 37: 281–5
Mateu-Navarro M, Rami-Porta R, Bastus-Piulats R, et al. Remediastinoscopy after induction chemotherapy in non-small cell lung cancer. Ann Thorac Surg 2000; 70: 391–5
De Leyn P, Stroobants S, De Wever W, et al. Prospective comparative study of integrated positron emission tomography-computed tomography scan compared with remediastinoscopy in the assessment of residual mediastinal lymph node disease after induction chemotherapy for mediastinoscopyproven stage IIIA-N2 non-small-cell lung cancer: a Leuven Lung Cancer Group Study. J Clin Oncol 2006; 24: 3333–9
Solomon B, Mitchell JD, Bunn PA. Adjuvant chemotherapy for resected non-small cell lung cancer. Oncology 2005; 19: 1685–97
Fleck CJ, Camargo K, Godoy D, et al. Chemoradiation therapy (CRT) versus chemotherapy (CT) alone as neo-adjuvant treatment for stage III non-small cell lung cancer (NSCLC): preliminary report of a phase III prospective randomized trial [abstract 1108]. Proc Am Soc Clin Oncol 1993; 12: 333
Sauvaget RJ-L, Rebischung J, Vannetzel J-M, et al. Phase III study of neo-adjuvant MVP versus MVP plus chemoradiotherapy in stage III disease [abstract]. Proc Am Soc Clin Oncol 2000; 19: a1935
Ruebe C, Riesenbeck D, Semik M, et al. Neoadjuvant chemotherapy followed by preoperative radiochemotherapy plus surgery or surgery plus post-operative radiotherapy in stage III non-small cell lung cancer: results of a randomized phase III trial of the German Lung Cancer Cooperative Group [abstract]. Int J Radiat Oncol Biol Phys 2004; 60: S130
Acknowledgements
No sources of funding were used to assist in the preparation of this review. The authors have no conflicts of interest that are directly relevant to the content of this review.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Stinchcombe, T.E., Socinski, M.A. The Role of Induction Therapy for Resectable Non-Small Cell Lung Cancer. Drugs 67, 321–332 (2007). https://doi.org/10.2165/00003495-200767030-00001
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003495-200767030-00001