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14 - Medical treatment of lung cancer (neo and adjuvant chemoradiotherapy)

from Section IV - Malignant conditions of the lung

Published online by Cambridge University Press:  05 September 2016

By
Athanasios G. Pallis  and
Mary E. R. O'Brien
Edited by
Marco Scarci ,
Aman Coonar ,
Tom Routledge  and
Francis Wells
Athanasios G. Pallis
Affiliation:
European Organization for Research and Treatment of Cancer Lung Cancer Group, Brussels, Belgium
Mary E. R. O'Brien
Affiliation:
The Lung Unit, Royal Marsden Hospital
Marco Scarci
Affiliation:
University College London Hospital
Aman Coonar
Affiliation:
Papworth Hospital
Tom Routledge
Affiliation:
Guy’s Hospital
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Summary

Adjuvant chemotherapy after surgical resection

Surgery remains the only curative treatment modality for patients with stage I–IIIA non-small cell lung cancer (NSCLC). However, even after complete resection, the risk of recurrence is substantial, and 5-year overall survival (OS) is approximately 70% for patients with stage IB disease, 40–50% for stage II and less than 30% for stage IIIA patients. Efforts to improve the survival of patients with operable NSCLC have examined the addition of chemotherapy (CMT) and/or radiotherapy (RT) in the post-operative setting.

In 1995, the NSCLC collaborative group reported a meta-analysis of eight trials with a total of 1394 patients treated with cisplatin-based adjuvant chemotherapy. This study reported a 13% reduction in the risk of death (hazard ratio [HR] 0.87; 95% confidence interval [CI]: 0.74–1.02) corresponding to an absolute survival benefit of 3% at 2 years (95% CI 0.5% detriment to 7% benefit) and 5% (95% CI 1% detriment to 10% benefit) at 5 years in favour of chemotherapy. Despite the lack of statistical significance (P = 0.08), these findings encouraged the initiation of several randomized trials investigating the role of platinum-based adjuvant chemotherapy in patients with completely resected stage I, II and IIIA NSCLC (Table 14.1).

The North American Intergroup Trial INT0115 was the only trial that compared the combination of chemotherapy plus thoracic radiotherapy versus radiotherapy alone in patients with completely resected stage II or IIIA NSCLC and failed to demonstrate a benefit in favour of chemotherapy. The negative results of the Adjuvant Lung Project Italy (ALPI) and the Big Lung Trial (BIG) further jeopardized the role of adjuvant chemotherapy in the treatment of NSCLC.

National Cancer Institute of Canada (NCIC) JBR10 trial

The National Cancer Institute of Canada (NCIC) JBR10 Trial randomly assigned 482 patients with completely resected, pathological stage IB and II (patients with T3N0 disease were excluded) to receive either post-operative adjuvant chemotherapy with cisplatin and vinorelbine or no chemotherapy.

At 5 years of follow-up, the 5-year survival rates were 69% for the chemotherapy arm and 54% for the control arm (HR 0.69; 95% CI 0.52–0.92; P = 0.011), with an absolute survival benefit of 15% for patients receiving chemotherapy.

Type
Chapter
Information
Core Topics in Thoracic Surgery , pp. 140 - 149
Publisher: Cambridge University Press
Print publication year: 2016

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References

1 Groome, PA, Bolejack, V, Crowley, JJ, et al. The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol 2007; 2:694–705.Google Scholar
2 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.
3 Keller, SM, Adak, S, Wagner, H, et al. 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 2000; 343:1217–22.Google Scholar
4 Scagliotti, GV, Fossati, R, Torri, V, et al. Randomized study of adjuvant chemotherapy for completely resected stage I, II, or IIIA non-small-cell Lung cancer. J Natl Cancer Inst 2003; 95:1453–61.Google Scholar
5 Waller, D, Peake, MD, Stephens, RJ, et al. Chemotherapy for patients with non-small cell lung cancer: the surgical setting of the Big Lung Trial. Eur J Cardiothorac Surg 2004; 26:173–82.Google Scholar
6 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.Google Scholar
7 Butts, CA, Ding, K, Seymour, L, et al. Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: updated survival analysis of JBR-10. J Clin Oncol 2010; 28:29–34.Google Scholar
8 Bezjak, A, Lee, CW, Ding, K, et al. Quality-of-life outcomes for adjuvant chemotherapy in early-stage non-small-cell lung cancer: results from a randomized trial, JBR.10. J Clin Oncol 2008; 26:5052–9.Google Scholar
9 Douillard, JY, Rosell, R, De, LM, et al. 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 2006; 7:719–27.Google Scholar
10 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.Google Scholar
11 Arriagada, R, Dunant, A, Pignon, JP, et al. Long-term results of the international adjuvant lung cancer trial evaluating adjuvant cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol 2010; 28:35–42.Google Scholar
12 Strauss, GM, Herndon, JE, Maddaus, MA, et al. Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer: CALGB 9633 with the Cancer and Leukemia Group B, Radiation Therapy Oncology Group and North Central Cancer Treatment Group Study Groups. J Clin Oncol 2008; 26:5043–51.Google Scholar
13 Kato, H, Ichinose, Y, Ohta, M, et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med 2004; 350:1713–21.Google Scholar
14 Hamada, C, Tanaka, F, Ohta, M, et al. Meta-analysis of postoperative adjuvant chemotherapy with tegafur-uracil in non-small-cell lung cancer. J Clin Oncol 2005; 23:4999–5006.Google Scholar
15 Goss, G, Lorimer, I, Tsao, MS, et al. A phase III randomized, double-blind, placebo-controlled trial of the epidermal growth factor receptor inhibitor gefitinb in completely resected stage IB-IIIA non-small cell lung cancer (NSCLC): NCIC CTG BR.19. J Clin Oncol 2010; 28:abstr LBA7005.Google Scholar
16 Sienel, W, Varwerk, C, Linder, A, et al. Melanoma associated antigen (MAGE)–A3 expression in stages I and II non-small cell lung cancer: results of a multi-center study. Eur J Cardiothorac Surg 2004; 25:131–4.Google Scholar
17 Pignon, JP, Tribodet, H, Scagliotti, GV, et al. Lung Adjuvant Cisplatin Evaluation: a pooled Analysis by the LACE Collaborative Group. J Clin Oncol 2008; 26:3552–9.Google Scholar
18 Arriagada, R, Auperin, A, Burdett, S, et al. Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data. Lancet 2010; 375:1267–77.Google Scholar
19 Hotta, K, Matsuo, K, Ueoka, H, et al. Role of adjuvant chemotherapy in patients with resected non-small-cell lung cancer: reappraisal with a meta-analysis of randomized controlled trials. J Clin Oncol 2004; 22:3860–7.Google Scholar
20 Sedrakyan, A, Meulen, J Van Der, O'Byrne, K, et al. Postoperative chemotherapy for non-small cell lung cancer: a systematic review and meta-analysis. J Thorac Cardiovasc Surg 2004; 128:414–9.Google Scholar
21 Berghmans, T, Paesmans, M, Meert, AP, et al. Survival improvement in resectable non-small cell lung cancer with (neo)adjuvant chemotherapy: results of a meta-analysis of the literature. Lung Cancer 2005; 49:13–23.Google Scholar
22 Bria, E, Gralla, RJ, Raftopoulos, H, et al. Magnitude of benefit of adjuvant chemotherapy for non-small cell lung cancer: meta-analysis of randomized clinical trials. Lung Cancer 2009; 63:50–7.Google Scholar
23 Scott, WJ, Howington, J, Feigenberg, S, et al. Treatment of non-small cell lung cancer stage I and stage II: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007; 132:234S–42S.Google Scholar
24 Pisters, KM, Evans, WK, Azzoli, CG, et al. 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 2007; 25:5506–18.Google Scholar
25 Crino, L, Weder, W, Meerbeeck, JP Van, et al. Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2010; 21:103–15.Google Scholar
26 Pallis, AG, Scarci, M. Are we treating enough elderly patients with early stage non-small cell lung cancer? Lung Cancer 2011; 74:149–54.Google Scholar
27 Fruh, M, Rolland, E, Pignon, JP, et al. Pooled analysis of the effect of age on adjuvant cisplatin-based chemotherapy for completely resected non-small-cell lung cancer. J Clin Oncol 2008; 26:3573–81.Google Scholar
28 Pepe, C, Hasan, B, Winton, TL, et al. Adjuvant vinorelbine and cisplatin in elderly patients: National Cancer Institute of Canada and Intergroup Study JBR.10. J Clin Oncol 2007; 25:1553–61.Google Scholar
29 Wisnivesky, JP, Smith, CB, Packer, S, et al. Survival and risk of adverse events in older patients receiving postoperative adjuvant chemotherapy for resected stages II–IIIA lung cancer: observational cohort study. BMJ 2011; 343:d4013.Google Scholar
30 Pallis, AG, Gridelli, C, Meerbeeck, JP van, et al. EORTC Elderly Task Force and Lung Cancer Group and International Society for Geriatric Oncology (SIOG) experts’ opinion for the treatment of non-small-cell lung cancer in an elderly population. Ann Oncol 2010; 21:692–706.Google Scholar
31 Pallis, AG, Karamouzis, MV. DNA repair pathways and their implication in cancer treatment. Cancer Metastasis Rev 2010; 29:677–85.Google Scholar
32 Olaussen, KA, Dunant, A, Fouret, P, et al. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med 2006; 355:983–91.Google Scholar
33 Kamal, NS, Soria, JC, Mendiboure, J, et al. MutS homologue 2 and the long-term benefit of adjuvant chemotherapy in lung cancer. Clin Cancer Rese 2010; 16:1206–15.Google Scholar
34 Zhu, CQ, Ding, K, Strumpf, D, et al. Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer. J Clin Oncol 2010; 28:4417–24.Google Scholar
35 Postoperative radiotherapy in non-small-cell lung cancer: systematic review and meta-analysis of individual patient data from nine randomised controlled trials. PORT Meta-analysis Trialists Group. Lancet 1998; 352:257–63.
36 Burdett, S, Stewart, L. Postoperative radiotherapy in non-small-cell lung cancer: update of an individual patient data meta-analysis. Lung Cancer 2005; 47:81–3.Google Scholar
37 Okawara, G, Ung, YC, Markman, BR, et al. Postoperative radiotherapy in stage II or IIIA completely resected non-small cell lung cancer: a systematic review and practice guideline. Lung Cancer 2004; 44:1–11.Google Scholar
38 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.Google Scholar
39 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.Google Scholar
40 Depierre, A, Milleron, B, Moro-Sibilot, D, et al. Preoperative chemotherapy followed by surgery compared with primary surgery in resectable stage I (except T1N0), II, and IIIa non-small-cell lung cancer. J Clin Oncol 2002; 20:247–53.Google Scholar
41 Westeel, V, Milleron, B, Quoix, E, et al. Long-term results of the French randomized trial comparing neoadjuvant chemotherapy followed by surgery versus surgery alone in resectable non-small cell lung cancer. J Clin Oncol 2010; 28:abstr 7003.Google Scholar
42 Scagliotti, GV, Pastorino, U, steenkiste, JF Van, et al. Randomized phase III study of surgery alone or surgery plus preoperative cisplatin and gemcitabine in stages IB to IIIA non-small-cell lung cancer. J Clin Oncol 2012; 30:172–8.Google Scholar
43 Gilligan, D, Nicolson, M, Smith, I, et al. Preoperative chemotherapy in patients with resectable non-small cell lung cancer: results of the MRC LU22/NVALT 2/EORTC 08012 multicentre randomised trial and update of systematic review. Lancet 2007; 369:1929–37.Google Scholar
44 Pisters, KM, Vallieres, E, Crowley, JJ, et al. Surgery with or without preoperative paclitaxel and carboplatin in early-stage non-small-cell lung cancer: Southwest Oncology Group Trial S9900, an intergroup, randomized, phase III trial. J Clin Oncol 2010; 28:1843–9.Google Scholar
45 Felip, E, Rosell, R, Maestre, JA, et al. Preoperative chemotherapy plus surgery versus surgery plus adjuvant chemotherapy versus surgery alone in early-stage non-small-cell lung cancer. J Clin Oncol 2010; 28:3138–45.Google Scholar
46 Bradbury, PA, Shepherd, FA. Chemotherapy and surgery for operable NSCLC. Lancet 2007; 369:1903–4.Google Scholar
47 Albain, KS, Rusch, VW, Crowley, JJ, et al. 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 1995; 13:1880–92.Google Scholar
48 Choi, NC, Carey, RW, Daly, W, et al. Potential impact on survival of improved tumor downstaging and resection rate by preoperative twice-daily radiation and concurrent chemotherapy in stage IIIA non-small-cell lung cancer. J Clin Oncol 1997; 15:712–22.Google Scholar
49 Eberhardt, W, Wilke, H, Stamatis, G, et al. 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 1998; 16:622–34.Google Scholar
50 Thomas, M, Rube, C, Hoffknecht, P, et al. Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer. Lancet Oncol 2008; 9:636–48.Google Scholar

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