Zusammenfassung
Biologische zielgerichtete („targeted”) Therapien haben den Weg vom Labor in die Klinik
gefunden. Durch die Identifizierung biologischer Zielstrukturen mit ihren Signaltransduktionswegen
konnten spezifische Therapieverfahren entwickelt werden. In der Zweit- und Drittlinientherapie
gehören die EGFR-Thyrosinkinasen-Inhibitoren als „targeted therapies” zum Standard
beim nicht kleinzelligen Lungenkarzinom (NSCLC), die VEGF-Antikörper konnten sich
in einer Phase-III-Studie in der Erstlinientherapie des NSCLC als besser als eine
alleinige Chemotherapie wirksam platzieren, und in allen anderen Indikationen und
Stadien laufen klinische Studien.
Wesentlicher Vorteil ist eine gute Verträglichkeit und die zum Teil orale Gabe der
Therapie.
Die einzelnen Zielstrukturen und die gegen sie gerichteten Medikamente werden vorgestellt
und ihr Stellenwert beim Lungenkarzinom diskutiert.
Abstract
An increased understanding of the biology of lung cancer has identified biological
targets for rationally designed novel therapies. Most of these targets are components
of signalling pathways or metabolic processes. EGFR-tyrosinkinase inhibitors have
become standard in second- and thirdline therapy of NSCLC, the anti-VEGF-antibody
Avastin combined with first-line chemotherapy showed a significant survival benefit
over chemotherapy alone. There are ongoing studies with targeted therapies in all
stages of lung cancer.
Major advances of these new drugs are their low toxicity and, in part, the oral application.
Literatur
- 1
Mendelsohn J, Baselga J.
Status of epidermal growth factor receptor antagonists in the biology and treatment
of cancer.
J Clin Oncol.
2003;
21
2787-2799
- 2
Shepherd F A, Pereira J R, Ciuleanu T. et al .
NCIC Canada: Erlotinib in previously treated non-small-cell lung cancer.
N Engl J Med.
2005;
353;2
123-132
- 3
Giaccone G, Herbst R S, Manegold C. et al .
Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell
lung cancer: a phase III trial - INTACT 1.
J Clin Oncol.
2004;
22
777-784
- 4
Herbst R S, Giaccone G, Schiller J H. et al .
Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell
lung cancer: a phase III trial - INTACT 2.
J Clin Oncol.
2004;
22
785-794
- 5
Gatzemeier U, Pluzanska A, Szczesna A. et al .
Results of a phase III trial of erlotinib (OSI-774) combined with cisplatin and gemcitabine
(GC) chemotherapy in advanced non-small cell lung cancer (NSCLC).
J Clin Oncol 2004; 23.
(suppl;
abstr 7010)
619s
- 6
Herbst R S, Prager D, Hermann R. et al .
TRIBUTE: a phase II trial of erlotinib hydrochloride (OSI-774) combined with carboplatin
and paclitaxel chemotherapy in advanced non-small-cell lung cancer.
J Clin Oncol.
2005;
23
5892-5899
- 7
Kelly K, Gaspar L, Chansky K. et al .
Low incidence of pneumonitis on SWOG 0023: a preliminary analysis of an ongoing phase
III trial of concurrent chemoradiotherapy followed by consolidation docetaxel and
Iressa/placebo maintenance in patients with inoperable stage III non-small cell lung
cancer.
Proc Am Soc Clin Oncol.
2005;
23
7058
- 8
Fukuoka M, Yano S, Giaccone G. et al .
Multi-institutional randomized phase II trial of gefitinib for previously treated
patients with advanced non-small-cell lung cancer (The IDEAL 1 Trial).
J Clin Oncol.
2003;
21
2237-2246
- 9
Kris M G, Natale R B, Herbst R S. et al .
Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine
kinase, in symptomatic patients with non-small cell lung cancer: a randomized trial.
JAMA.
2003;
290
2149-2158
- 10
Ochs J, Grous J, Warner K.
Final survival and safety results for 21 064 non-small-cell lung cancer (NSCLC) patients
who received compassionate use gefitinib in a U.S. expanded program (EAP).
J Clin Oncol 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
2004;
22 (14 Suppl)
7060
- 11
Thatcher N, Chang A, Parikh P. et al .
Gefitinib plus best supportive care in previously treated patients with refractory
advanced non-small-cell lung cancer: results from a randomized, placebo controlled,
multicenter study (Iressa Survival Evaluation in Lung Cancer).
Lancet.
2005;
366
1527-1537
- 12
Robinet G, Berard H, Chouaid C. et al .
A phase II trial of Docetaxel alone and in combination with Gefitinib as second-line
chemotherapy for patients with non-small cell lung cancer.
Ann Oncol.
2004;
15 (Suppl. 3)
iii183
- 13
Miller V A, Kris M G, Shah N. et al .
Bronchioalveolar pathologic subtype and smoking history predict sensitivity to gefitinib
in advanced non-small-cell lung cancer.
J Clin Oncol.
2004;
22
1103-1109
- 14
Lilenbaum R, Axerold R, Thomas S. et al .
Bodkin Randomized phase II trial of single agent erlotinib vs. standard chemotherapy
in patients with advanced non-small cell lung cancer (NSCLC) and performance status
(PS) of 2.
Proc Am Soc Clin Oncol.
2006;
#7022
- 15
Perez-Soler R, Chachoua A, Hammond L A. et al .
Determinants of tumor response and survival with erlotinib in patients with non-small-cell
lung cancer.
J Clin Oncol.
2004;
22
3238-3247
- 16
Tsao M-S, Sakurada A, Cutz J-C. et al .
Erlotinib and lung cancer - molecular and clinical predictors of outcome.
N Engl J Med..
2005;
353
133-144
- 17
Cappuzzo F, Hirsch F R, Rossi E. et al .
Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell
lung cancer.
J Natl Cancer Inst.
2005;
97
643-655
- 18
Hirsch F R, Varella-Garcia M, Bunn Jr P. et al .
Molecular Predictors of Outcome With Gefitinib in a Phase III Placebo-Controlled Study
in Advanced Non-Small-Cell Lung Cancer.
Journal of Clinical Oncology.
2006;
24 (31)
5034-5042
- 19
Rosell R, Daniel C, Ramlau R. et al .
Randomized phase II study of cetuximab in combination with cisplatin (C) and vinorelbine
(V) vs CV alone in the first-line treatment of patients with epidermal growth factor
receptor (EGFR)-expressing advanced non-small call lung cancer.
J Clin Oncol 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
2004;
22 (14 Suppl)
7012
- 20
Kelly K, Gaspar L, Chansky K. et al .
Low incidence of pneumonitis on SWOG 0023: a preliminary analysis of an ongoing phase
III trial of concurrent chemoradiotherapy followed by consolidation docetaxel and
Iressa/placebo maintenance in patients with inoperable stage III non-small cell lung
cancer.
Proc Am Soc Clin Oncol.
2005;
23
7058
- 21
Sandler A B, Gray R, Brahmer J. et al .
Randomized phase II/III trial of paclitaxel (P) plus carboplatin (C) with or without
bevacizumab (NSC#704 865) in patients with advanced non-squamous non-small cell lung
cancer (NSCLC): an Eastern Cooperative Oncology Group (ECOG) trial - E4599.
J Clin Oncol.
2005;
23 (suppl)
16S
- 22
Fehrenbacher L, O'Neill V, Belani C P. et al .
A phase II, multicenter, randomized clinical trial to evaluate the efficacy and safety
of bevacizumab in combination with either chemotherapy (docetaxel or pemetrexed) or
erlotinib hydrochloride compared with chemotherapy alone for treatment of recurrent
or refractory non-small cell lung cancer.
Proc Am Soc Clin Oncol.
2006;
24 Abstract 7062
379s
- 23
Heymach V, Johnson B E, Prager D. et al .
A phase II trial of ZD6474 plus docetaxel in patients with previously treated NSCLC:
follow-up results.
Proc Am Soc Clin Oncol.
2006;
24 Abstract 7016
368s
- 24
Socinski M, Novello S, Sanchez J. et al .
Efficacy and safety of sunitinib in previously treated, advanced non-small cell lung
cancer (NSCLC): preliminary results of a multicenter phase II trial.
Proc Am Soc Clin Oncol.
2006;
24 Abstract 7001
364s
- 25
Gatzemeier U, Blumenschein G, Fosella F. et al .
Phase II trial of single-agent sorafenib in patients with advanced non-small cell
lung carcinoma.
Proc Am Soc Clin Oncol.
2006;
#7002
- 26
Pawel J von, Roemeling R von, Gatzemeier U. et al .
Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer:
A report of the international CATAPULT I study group-Cisplatin and Tirapazamine in
Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors.
J Clin Oncol.
2000;
18
1351-1359
- 27
Lynch T J, Raju R, Lind M. et al .
Randomized phase III trial of chemotherapy and antisense, oligonucleotide LY9000003
(ISIS 3521) in patients with advanced NSCLC: Initial report.
Proc Am Soc Clin Oncol.
2003;
22 (abstr 2504)
623
Dr. med. Monika Serke
Helios-Klinikum Emil von Behring, Lungenklinik Heckeshorn, Pneumologie
Walterhöferstr. 11
14165 Berlin
Email: m.serke@berlin-behring.helios-kliniken.de