Systemische Behandlung nicht kleinzelliger und kleinzelliger Lungenkarzinome – Multimodale und molekulare Therapiekonzepte

Lars Henning Schmidt; Tillman Spieker; Michael Mohr; Torsten Kessler; Karsten Wiebe; Carsten Müller-Tidow; Wolfgang E Berdel; Rainer Wiewrodt

doi:10.1055/s-0031-1301061

Der Klinikarzt 2011; 40(12): 566-575
DOI: 10.1055/s-0031-1301061

Schwerpunkt

Systemische Behandlung nicht kleinzelliger und kleinzelliger Lungenkarzinome – Multimodale und molekulare Therapiekonzepte

Systemic treatment in non-small cell lung cancer and small cell lung cancer – Multimodal therapy concepts and palliative care

Authors

Lars Henning Schmidt

¹Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster
Tillman Spieker

²Institut für Pathologie, Universitätsklinikum Münster
Michael Mohr

¹Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster
Torsten Kessler

¹Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster
Karsten Wiebe

³Klinik für Thorax-, Herz- und Gefäßchirurgie, Universitätsklinikum Münster
Carsten Müller-Tidow

¹Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster
Wolfgang E Berdel

¹Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster
Rainer Wiewrodt

¹Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster

Abstract

Die Therapie des Lungenkarzinoms ist multidisziplinär und basiert neben klinischen, radiologischen und histologischen Kriterien auch auf molekularen Befunden. Grundsätzlich unterscheidet sich die Behandlung nicht kleinzelliger Lungenkarzinome (NSCLC) von der kleinzelliger Lungenkarzinome (SCLC). Werden nicht kleinzellige Lungenkarzinome in den Stadien I und II (gegebenenfalls auch im Stadium IIIA) in kurativer Intention reseziert, so rücken in den fortgeschrittenen Stadien multimodale Therapiekonzepte bestehend aus Chemo- und Radiotherapie in den Fokus. In metastasierten Stadien sind platinbasierte Kombinationstherapien etabliert. Insbesondere diese Patientengruppe benötigt eine umfassende palliative Versorgung. Die Testung molekularer Faktoren wie EGFR oder EML-4-ALK ermöglicht immer häufiger den Einsatz neuer zielgerichteter Therapeutika und kann zu einer verbesserten Prognose beitragen. Charakteristisch für die Therapie des kleinzelligen Lungenkarzinoms ist hingegen ein inital oftmals gutes Ansprechen auf die Behandlung – bei gleichzeitig hoher Rezidivneigung. In dieser Situation haben platinbasierte Kombinationschemotherapien unverändert einen festen Stellenwert. Abhängig von der Ausdehnung des Tumors werden diese auch um strahlentherapeutische Verfahren erweitert.

Lung cancer treatment is a multidisciplinary approach and is based on clinical, radiologic, histologic and molecular decisions. In principle, treatment of non-small cell lung cancer (NSCLC) differs from small cell lung cancer (SCLC). Whereas NSCLC in stage I and II (also stage IIIA when indicated) undergo curative resection, multimodal therapy concepts, consisting of chemotherapy and radiotherapy receive priority in advanced stages. In metastasized settings platin-based chemotherapy combinations are established. Especially these patients need extensive palliative care. Testing for molecular factors (i. e. EGFR or EML-4-ALK) offers the application of molecular targeted therapies in order to improve the prognosis. Therapy of SCLC however is characterized by an initially good response with strong relapse tendency. Still platin-based chemotherapy combinations are the therapy of choice for SCLC. Depending on tumor-size and tumor spread radiotherapeutic approaches are applied in addition.

Key words

NSCLC - SCLC - multimodal therapy concepts - individualised therapy - receptor tyrosine kinases - EGFR - palliative care - palliative regional therapy

Full Text

References

Literatur
1 Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol 2011; 12: 175-180
2 Ezzati M, Henley SJ, Lopez AD et al. Role of smoking in global and regional cancer epidemiology: current patterns and data needs. Int J Cancer 2005; 116: 963-971
3 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: 247-253
4 Yan TD, Black D, Bannon PG et al. Systematic review and meta-analysis of randomized and nonrandomized trials on safety and efficacy of video-assisted thoracic surgery lobectomy for early-stage non-small-cell lung cancer. J Clin Oncol 2009; 27: 2553-2562
5 Ginsberg RJ, Rubinstein LV. Randomized trial of lobectomy versus limited resection for T1 N0 non-small cell lung cancer. Lung Cancer Study Group. Ann Thorac Surg 1995; 60: 615-622
6 Mery CM, Pappas AN, Bueno R et al. Similar long-term survival of elderly patients with non-small cell lung cancer treated with lobectomy or wedge resection within the surveillance, epidemiology, and end results database. Chest 2005; 128: 237-245
7 Feng QF, Wang M, Wang LJ et al. A study of postoperative radiotherapy in patients with non-small-cell lung cancer: a randomized trial. Int J Radiat Oncol Biol Phys 2000; 47: 925-929
8 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: 351-360
9 Goeckenjan G, Sitter H, Thomas M et al. Prävention, Diagnose, Therapie und Nachsorge des Lungenkarzinoms. Interdisziplinäre S3-Leitlinie der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin und der Deutschen Krebsgesellschaft. Pneumologie 2010; 64 (Suppl. 02) 1-164
10 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
11 Lagerwaard FJ, Haasbeek CJ, Smit EF et al. Outcomes of risk-adapted fractionated stereotactic radiotherapy for stage I non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 2008; 70: 685-692
12 Robinson LA, Ruckdeschel JC, Wagner HJr. et al. Treatment of non-small cell lung cancer-stage IIIA: ACCP evidence-based clinical practice guidelines (2^nd edition). Chest 2007; 132 (Suppl. 03)
13 Goldstraw P, Crowley J, Chansky K et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol 2007; 2: 706-714
14 Albain KS, Swann RS, Rusch VW et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet 2009; 374: 379-386
15 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: 636-648
16 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: 1880-1892
17 Tanvetyanon T, Robinson LA, Schell MJ et al. Outcomes of adrenalectomy for isolated synchronous versus metachronous adrenal metastases in non-small-cell lung cancer: a systematic review and pooled analysis. J Clin Oncol 2008; 26: 1142-1147
18 No authors listed. 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
19 No authors listed. 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 2008; 26: 4617-4625
20 Scagliotti GV, Parikh P, von PJ et al. 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 2008; 26: 3543-3551
21 Davidoff AJ, Tang M, Seal B et al. Chemotherapy and survival benefit in elderly patients with advanced non-small-cell lung cancer. J Clin Oncol 2010; 28: 2191-2197
22 Quoix EA, Oster J, Westeel V et al. Weekly paclitaxel combined with monthly carboplatin versus single-agent therapy in patients age 70 to 89: IFCT-0501 randomized phase III study in advanced non-small cell lung cancer (NSCLC). J Clin Oncol abstract 2010; 28 (Suppl. 01)
23 Becker G, Hatami I, Xander C et al. Palliative cancer care: an epidemiologic study. J Clin Oncol 2011; 29: 646-650
24 Temel JS, Greer JA, Muzikansky A et al. Early palliative care for patients with metastatic non-small-cell lung cancer. N Engl J Med 2010; 363: 733-742
25 Sandler A, Gray R, Perry MC et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 2006; 355: 2542-2550
26 Reck M, von PJ, Zatloukal P et al. Phase III trial of cisplatin plus gemcitabine with either placebo or bevacizumab as first-line therapy for nonsquamous non-small-cell lung cancer: AVAil. J Clin Oncol 2009; 27: 1227-1234
27 Appelmann I, Liersch R, Kessler T et al. Angiogenesis inhibition in cancer therapy: platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) and their receptors: biological functions and role in malignancy. Recent Results Cancer Res 2010; 180: 51-81
28 Mok TS, Wu YL, Thongprasert S et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 2009; 361: 947-957
29 Mitsudomi T, Morita S, Yatabe Y et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial. Lancet Oncol 2010; 11: 121-128
30 Maemondo M, Inoue A, Kobayashi K et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N Engl J Med 2010; 362: 2380-2388
31 Rosell R, Vergnenegre A, Massuti B et al. Erlotinib vs chemotherapy (CT) in advanced non-small-cell lung cancer (NSCLC) patients (p) with epidermal growth factor receptor (EGFR) activating mutations: Interim results of the European Erlotinib Versus Chemotherapy (EURTAC) phase III randomized trial. J Clin Oncol ASCO 2011, abstract 7503 2011; 29 (Suppl. 01)
32 Jackman D, Pao W, Riely GJ et al. Clinical definition of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small-cell lung cancer. J Clin Oncol 2010; 28: 357-360
33 Stinchcombe TE, Socinski MA. Maintenance therapy in advanced non-small cell lung cancer: current status and future implications. J Thorac Oncol 2011; 6: 174-182
34 Ciuleanu T, Brodowicz T, Zielinski C et al. Maintenance pemetrexed plus best supportive care versus placebo plus best supportive care for non-small-cell lung cancer: a randomised, double-blind, phase 3 study. Lancet 2009; 374: 1432-1440
35 Cappuzzo F, Ciuleanu T, Stelmakh L et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol 2010; 11: 521-529
36 Fidias PM, Dakhil SR, Lyss AP et al. Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol 2009; 27: 591-598
37 Soon YY, Stockler MR, Askie LM et al. Duration of chemotherapy for advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomized trials. J Clin Oncol 2009; 27: 3277-3283
38 Kris MG, Johnson BE, Kwiatkowski DJ et al. Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: The NCI's Lung Cancer Mutation Consortium (LCMC). J Clin Oncol ASCO 2011, Abstract ACR 7506 2011; 29 (Suppl. 01)
39 Sequist LV, Heist RS, Shaw AT et al. Implementing multiplexed genotyping of non-small-cell lung cancers into routine clinical practice. Ann Oncol 2011; 22: 2616-2624
40 Kwak EL, Bang YJ, Camidge DR et al. Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 2010; 363: 1693-1703
41 Horn L, Pao W. EML4-ALK: honing in on a new target in non-small-cell lung cancer. J Clin Oncol 2009; 27: 4232-4235
42 Hanna N, Shepherd FA, Fossella FV et al. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J Clin Oncol 2004; 22: 1589-1597
43 Ramlau R, Gervais R, Krzakowski M et al. Phase III study comparing oral topotecan to intravenous docetaxel in patients with pretreated advanced non-small-cell lung cancer. J Clin Oncol 2006; 24: 2800-2807
44 Krzakowski M, Ramlau R, Jassem J et al. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy. J Clin Oncol 2010; 28: 2167-2173
45 Kim ES, Hirsh V, Mok T et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase III trial. Lancet 2008; 372: 1809-1818
46 Shepherd FA, Rodrigues PJ, Ciuleanu T et al. Erlotinib in previously treated non-small-cell lung cancer. N Engl J Med 2005; 353: 123-132
47 Colice GL, Rubins J, Unger M. Follow-up and surveillance of the lung cancer patient following curative-intent therapy. Chest 2003; 123 (Suppl. 01)
48 Stupp R, Monnerat C, Turrisi III AT et al. Small cell lung cancer: state of the art and future perspectives. Lung Cancer 2004; 45: 105-117
49 Fried DB, Morris DE, Poole C et al. Systematic review evaluating the timing of thoracic radiation therapy in combined modality therapy for limited-stage small-cell lung cancer. J Clin Oncol 2004; 22: 4837-4845
50 Turrisi 3rd AT, Kim K, Blum R et al. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999; 340: 265-271
51 Meert AP, Paesmans M, Berghmans T et al. Prophylactic cranial irradiation in small cell lung cancer: a systematic review of the literature with meta-analysis. BMC Cancer 2001; 1: 5-5
52 Slotman BJ, Mauer ME, Bottomley A et al. Prophylactic cranial irradiation in extensive disease small-cell lung cancer: short-term health-related quality of life and patient reported symptoms: results of an international phase III randomized controlled trial by the EORTC Radiation Oncology and Lung Cancer Groups. J Clin Oncol 2009; 27: 78-84
53 Schreiber D, Rineer J, Weedon J et al. Survival outcomes with the use of surgery in limited-stage small cell lung cancer: should its role be re-evaluated?. Cancer 2010; 116: 1350-1357
54 Giaccone G, Ferrati P, Donadio M et al. Reinduction chemotherapy in small cell lung cancer. Eur J Cancer Clin Oncol 1987; 23: 1697-1699
55 Hammerman P, Sivachenko A, Cherniak A et al. Genomic characterization and targeted therapeutics in squamous cell lung cancer; 14^th World Conference on Lung Cancer 2011, Abstract. 1161;
56 Gandara DR, Mack PC, Li T et al. Evolving treatment algorithms for advanced non-small-cell lung cancer: 2009 looking toward 2012. Clin Lung Cancer 2009; 10: 392-394