Aktuelle Therapiekonzepte des Lungenkarzinoms

Zusammenfassung

Das Lungenkarzinom ist mit einem medianen Erkrankungsalter von 69 Jahren eine Erkrankung des höheren Lebensalters. Die Hauptursache ist das Zigarettenrauchen. Für beide Geschlechter ist das Lungenkarzinom die dritthäufigste Tumorerkrankung in Deutschland. Während bei operablen Tumorstadien in 30 – 80 % der Patienten ein Langzeitüberleben erreicht werden kann, ist die Prognose im fernmetastasierten Stadium ungünstig mit 5-Jahres-Überlebensraten von 6 % für das kleinzellige Lungenkarzinom (SCLC) und 18 % für das nicht-kleinzellige Lungenkarzinom (NSCLC). Aufgrund der ungünstigen Prognose wird intensiv an der Verbesserung der Therapie des Lungenkarzinoms gearbeitet. Dieser Artikel gibt einen Überblick zu den aktuellen therapeutischen Möglichkeiten und Ansätzen.

Abstract

Lung cancer occurs with a median age of 69 years. The main cause is cigarette smoking. For both genders lung cancer is the third-most frequent tumor in Germany. While in an operable tumor stage 30 – 80 % of the patients can reach long-term survival, the prognosis in the metastasised stage is unfavourable with a 5-year overall survival rate of 6 % for small cell lung cancer (SCLC) and 18 % for non-small cell lung cancer (NSCLC). Lung cancer is subject of intense research to improve the outcome. This article gives an overview of current treatment options.

Schlüsselwörter

SCLC - NSCLC - Chemotherapie - Operation - Strahlentherapie - gezielte Therapie

Keywords

SCLC - NSCLC - chemotherapy - surgery - radiotherapy - targeted therapy

Literatur

• 1 Albain K S, Swann R S, Rusch V W. 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
• 2 Ardizzoni A, Hansen H, Dombernowsky P. et al . Topotecan, a new active drug in the second-line treatment of small-cell lung cancer: a phase II study in patients with refractory and sensitive disease.  J Clin Oncol. 1997;  15 2090-2096
• 3 Auperin A, Arriagada R, Pignon J P. et al . Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission.  N Engl J Med. 1999;  341 476-484
• 4 Berger D P, Engelhardt R, Mertelsmann R eds. Das Rote Buch: Hämatologie und internistische Onkologie. 4. ed. Landsberg/Lech: ecomed; 2010
• 5 Brock M V, Hooker C M, Syphard J E. et al . Surgical resection of limited disease small cell lung cancer in the new era of platinum chemotherapy: Its time has come.  J Thorac Cardiovasc Surg. 2005;  129 64-72
• 6 Burdett S S, Stewart L A, Rydzewska L. Chemotherapy and surgery versus surgery alone in non-small cell lung cancer.  Cochrane Database Syst Rev. 2007;  CD006157
• 7 Butts C A, 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
• 8 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
• 9 Carolan H, Sun A Y, Bezjak A. et al . Does the incidence and outcome of brain metastases in locally advanced non-small cell lung cancer justify prophylactic cranial irradiation or early detection?.  Lung Cancer. 2005;  49 109-115
• 10 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
• 11 Crino L, Weder W, van Meerbeeck J, Felip E. 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 Suppl 5 v103-115
• 12 D’Addario G, Fruh M, Reck M, Baumann P, Klepetko W, Felip E. Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.  Ann Oncol. 2010;  21 Suppl 5 v116-119
• 13 De Ruysscher D, Pijls-Johannesma M, Bentzen S M. et al . Time between the first day of chemotherapy and the last day of chest radiation is the most important predictor of survival in limited-disease small-cell lung cancer.  J Clin Oncol. 2006;  24 1057-1063
• 14 De Ruysscher D, Pijls-Johannesma M, Vansteenkiste J, Kester A, Rutten I, Lambin P. Systematic review and meta-analysis of randomised, controlled trials of the timing of chest radiotherapy in patients with limited-stage, small-cell lung cancer.  Ann Oncol. 2006;  17 543-552
• 15 Douillard J Y, Shepherd F A, Hirsh V. et al . Molecular predictors of outcome with gefitinib and docetaxel in previously treated non-small-cell lung cancer: data from the randomized phase III INTEREST trial.  J Clin Oncol. 2010;  28 744-752
• 16 Eckardt J R, von Pawel J, Pujol J L. et al . Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer.  J Clin Oncol. 2007;  25 2086-2092
• 17 Engelhardt M, Berger D P, Mertelsmann R eds. Das Blaue Buch: Chemotherapie-Manual Hämatologie und Onkologie.  3. ed. Berlin, Heidelberg, New York: Springer; 2010
• 18 Ferraldeschi R, Baka S, Jyoti B, Faivre-Finn C, Thatcher N, Lorigan P. Modern management of small-cell lung cancer.  Drugs. 2007;  67 2135-2152
• 19 Goeckenjan G, Sitter H, Thomas M. et al . Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms.  Pneumologie. 2010;  64 Suppl 2 e1-164
• 20 Goldstraw P. The 7th Edition of TNM in lung cancer: what now?.  J Thorac Oncol. 2009;  4 671-673
• 21 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
• 22 http://seer.cancer.gov letzter Zugriff: 1.7.2011
• 23 Hanagiri T, Sugio K, Baba T. et al . Results of surgical treatment for patients with small cell lung cancer.  J Thorac Oncol. 2009;  4 964-968
• 24 Hanna N, Bunn Jr P A, Langer C. et al . Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer.  J Clin Oncol. 2006;  24 2038-2043
• 25 Hanna N, Shepherd F A, Fossella F V. 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
• 26 Huber R M, Flentje M, Schmidt M. et al . Simultaneous chemoradiotherapy compared with radiotherapy alone after induction chemotherapy in inoperable stage IIIA or IIIB non-small-cell lung cancer: study CTRT99/97 by the Bronchial Carcinoma Therapy Group.  J Clin Oncol. 2006;  24 4397-4404
• 27 Husmann G, Kaatsch P, Katalinic A. et al .Krebs in Deutschland 2005/2006 Häufigkeiten und Trends. Berlin: Robert Koch-Institut (Hrsg); 2010
• 28 Inoue A, Kobayashi K, Usui K. et al . First-line gefitinib for patients with advanced non-small-cell lung cancer harboring epidermal growth factor receptor mutations without indication for chemotherapy.  J Clin Oncol. 2009;  27 1394-1400
• 29 Jett J R, Schild S E, Keith R L, Kesler K A. Treatment of non-small cell lung cancer, stage IIIB: ACCP evidence-based clinical practice guidelines (2nd edition).  Chest. 2007;  132 266S-276S
• 30 Jiang L, Yang K H, Mi D H. et al . Safety of irinotecan/cisplatin versus etoposide/cisplatin for patients with extensive-stage small-cell lung cancer: a metaanalysis.  Clin Lung Cancer. 2007;  8 497-501
• 31 Kim E S, 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
• 32 Kwak E L, Bang Y J, Camidge D R. et al . Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.  N Engl J Med. 2010;  363 1693-1703
• 33 Lester J F, Coles B, Macbeth F R. Prophylactic cranial irradiation for preventing brain metastases in patients undergoing radical treatment for non-small cell lung cancer.  Cochrane Database Syst Rev. 2005: CD005221; 
• 34 Livingston R B. Small cell carcinoma of the lung.  Blood. 1980;  56 575-584
• 35 Mok T S, Wu Y L, Thongprasert S. et al . Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.  N Engl J Med. 2009;  361 947-957
• 36 NSCLC Meta-Analyses Collaborative Group . 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
• 37 O’Brien M E, Ciuleanu T E, Tsekov H. et al . Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer.  J Clin Oncol. 2006;  24 5441-5447
• 38 Okamoto H, Watanabe K, Kunikane H. et al . Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702.  Br J Cancer. 2007;  97 162-169
• 39 Pennell N A, Lynch Jr T J. Combined inhibition of the VEGFR and EGFR signaling pathways in the treatment of NSCLC.  Oncologist. 2009;  14 399-411
• 40 Pöttgen C, Eberhardt W, Grannass A. et al . Prophylactic cranial irradiation in operable stage IIIA non small-cell lung cancer treated with neoadjuvant chemoradiotherapy: results from a German multicenter randomized trial.  J Clin Oncol. 2007;  25 4987-4992
• 41 Reck M, von Pawel J, Zatloukal P. et al . Overall survival with cisplatin-gemcitabine and bevacizumab or placebo as first-line therapy for nonsquamous non-small-cell lung cancer: results from a randomised phase III trial (AVAiL).  Ann Oncol. 2010;  21 1804-1809
• 42 Reck M, von Pawel J, 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
• 43 Rowell N P, Williams C J. Radical radiotherapy for stage I/II non-small cell lung cancer in patients not sufficiently fit for or declining surgery (medically inoperable).  Cochrane Database Syst Rev. 2001;  CD002935
• 44 Rusch V W, Giroux D J, Kraut M J. et al . Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung carcinomas: long-term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160).  J Clin Oncol. 2007;  25 313-318
• 45 Sandler A, Gray R, Perry M C. et al . Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer.  N Engl J Med. 2006;  355 2542-2550
• 46 Scagliotti G, Hanna N, Fossella F. et al . The differential efficacy of pemetrexed according to NSCLC histology: a review of two Phase III studies.  Oncologist. 2009;  14 253-263
• 47 Scagliotti G V, Parikh P, von Pawel J. 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
• 48 Schalhorn A. Moderne Chemotherapie beim Bronchialkarzinom.  Internist (Berl). 2002;  43 416-430
• 49 Schiller J H, Harrington D, Belani C P. et al . Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.  N Engl J Med. 2002;  346 92-98
• 50 Shepherd F A, Rodrigues Pereira J, Ciuleanu T. et al . Erlotinib in previously treated non-small-cell lung cancer.  N Engl J Med. 2005;  353 123-132
• 51 Simon G R, Turrisi A. Management of small cell lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition).  Chest. 2007;  132 324S-339S
• 52 Simon G R, Wagner H. Small cell lung cancer.  Chest. 2003;  123 259S-271S
• 53 Skarlos D V, Samantas E, Kosmidis P. et al . Randomized comparison of etoposide-cisplatin vs. etoposide-carboplatin and irradiation in small-cell lung cancer.  Ann Oncol. 1994;  5 601-607
• 54 Slotman B, Faivre-Finn C, Kramer G. et al . Prophylactic cranial irradiation in extensive small-cell lung cancer.  N Engl J Med. 2007;  357 664-672
• 55 Sorensen M, Pijls-Johannesma M, Felip E. Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.  Ann Oncol. 2010;  21 Suppl 5 v120-125
• 56 Strauss G M, Herndon 2nd J E, Maddaus M A. 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 5043-5051
• 57 Takeda K, Hida T, Sato T. et al . Randomized phase III trial of platinum-doublet chemotherapy followed by gefitinib compared with continued platinum-doublet chemotherapy in Japanese patients with advanced non-small-cell lung cancer: results of a west Japan thoracic oncology group trial (WJTOG0203).  J Clin Oncol. 2010;  28 753-760
• 58 Temel J S, Greer J A, Muzikansky A. et al . Early palliative care for patients with metastatic non-small-cell lung cancer.  N Engl J Med. 2010;  363 733-742
• 59 von Pawel J, Schiller J H, Shepherd F A. et al . Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer.  J Clin Oncol. 1999;  17 658-667