Skip to main content
SpringerLink
Log in

Neue Substanzen für die Therapie solider Tumoren

New agents for treatment of solid tumors

  • Fokus
  • Published:
Forum Aims and scope

Zusammenfassung

In den letzten Jahren konnten die systemtherapeutischen Optionen solider Tumoren weiterführend deutlich verbessert werden. Neben verschiedenen neuen und teilweise auch neuartigen („first in class“) molekular zielgerichteten Substanzen, z. B. Hedgehog-Signalweg-Inhibitoren und Inhibitoren der mitogenaktivierten extrazellulär regulierten Kinase (MEK) oder Fusionsproteine, wurden auch einige neue klassische zytotoxische Substanzen zugelassen bzw. zur Zulassung eingereicht. Allerdings sind nur einige wenige zytotoxische Substanzen gegenüber einer Vielzahl an molekular zielgerichteten Substanzen neu dazugekommen. Mittlerweile sind auch die ersten Konjugate aus Rezeptorantikörpern oder -liganden und zytotoxischen Substanzen für solide Tumoren verfügbar (Mammakarzinom und in Kürze Ovarialkarzinom). Besonders vielversprechend sind die Weiterentwicklung der seit einigen Jahren beim malignen Melanom eingesetzten immunmodulatorischen Therapie und deren Ausweitung auf neue Substanzen und Kombinationen sowie weitere Indikationsgebiete.

Abstract

Systemic treatment options for solid tumors have steadily improved during recent years. Besides several new and sometimes novel first in class molecular targeting agents, e.g. hedgehog and mitogen-activated or extracellular signal-regulated protein kinase (MEK) inhibitors or fusion proteins, some classical cytotoxic agents were licensed or submitted for approval. However, only very few cytotoxic agents have become available compared to a large number of molecular targeting agents. Interestingly, conjugates containing receptor antibodies or ligands and cytotoxic agents are now available for solid tumors (i.e. breast cancer and ovarian cancer soon to follow). Further development of immunomodulatory treatment which has already been used for malignant melanoma for several years, seems to be particularly promising with respect to evaluating new agents or combinations and extending the use towards other malignant diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1

Literatur

  1. Aghajanian C, Blank SV et al (2012) OCEANS: a randomized, double-blind, placebo-controlled phase III trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent epithelial ovarian, primary peritoneal, or fallopian tube cancer. J Clin Oncol 30:2039–2045

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Alberts SR, Sargent DJ et al (2012) Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA 307:1383–1393

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Baselga J, Campone M et al (2012) Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 366:520–529

    Article  CAS  PubMed  Google Scholar 

  4. Baselga J, Cortes J et al (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366:109–119

    Article  CAS  PubMed  Google Scholar 

  5. Brahmer JR, Tykodi SS et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Burger RA, Brady MF et al (2011) Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 365:2473–2483

    Article  CAS  PubMed  Google Scholar 

  7. Conroy T, Desseigne F et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med 364:1817–1825

    Article  CAS  PubMed  Google Scholar 

  8. Bono JS de, Logothetis CJ et al (2011) Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 364:1995–2005

    Article  PubMed Central  PubMed  Google Scholar 

  9. Gramont A de, Cutsem E van et al (2012) Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol 13:1225–1233

    Article  PubMed  Google Scholar 

  10. Elisei R, Schlumberger MJ et al (2013) Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol 31:3639–3646

    Article  CAS  PubMed  Google Scholar 

  11. Flaherty KT, Infante JR et al (2012) Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N Engl J Med 367:1694–1703

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Flaherty KT, Robert C et al (2012) Improved survival with MEK inhibition in BRAF-mutated melanoma. N Engl J Med 367:107–114

    Article  CAS  PubMed  Google Scholar 

  13. Friboulet L, Li N et al (2014) The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov (E-pub ahead of print)

  14. Fuchs CS, Tomasek J et al (2013) Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 383:31–39

    Article  PubMed  Google Scholar 

  15. Geyer CE, Forster J et al (2006) Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 355:2733–2743

    Article  CAS  PubMed  Google Scholar 

  16. Gianni L, Pienkowski T et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13:25–32

    Article  CAS  PubMed  Google Scholar 

  17. Grothey A, Cutsem EV et al (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381:303–312

    Article  CAS  PubMed  Google Scholar 

  18. Hamid O, Robert C et al (2013) Safety and tumor responses with Lambrolizumab (Anti-PD-1) in melanoma. N Engl J Med 369:134–144

    Article  CAS  PubMed  Google Scholar 

  19. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  20. Hauschild A, Grob JJ et al (2012) Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet 380:358–365

    Article  CAS  PubMed  Google Scholar 

  21. Hong DS, Hui D et al (2014) MABp1, a first-in-class true human antibody targeting interleukin-1alpha in refractory cancers: an open-label, phase 1 dose-escalation and expansion study. Lancet Oncol 15(6):656–666)

    Article  CAS  PubMed  Google Scholar 

  22. Kantoff PW, Higano CS et al (2010) Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 363:411–422

    Article  CAS  PubMed  Google Scholar 

  23. Kwak EL, Bang YJ et al (2010) Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer. N Engl J Med 363:1693–1703

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Le DT, Lutz E et al (2013) Evaluation of ipilimumab in combination with allogeneic pancreatic tumor cells transfected with a GM-CSF gene in previously treated pancreatic cancer. J Immunother 36:382–389

    Article  CAS  PubMed  Google Scholar 

  25. Ledermann J, Harter P et al (2012) Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 366:1382–1392

    Article  CAS  PubMed  Google Scholar 

  26. Lordick F, Kang YK et al (2013) Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol 14(6):490–499

    Article  CAS  PubMed  Google Scholar 

  27. Mok TS, Wu YL et al (2009) Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med 361:947–957

    Article  CAS  PubMed  Google Scholar 

  28. Naumann RW, Coleman RL et al (2013) PRECEDENT: a randomized phase II trial comparing vintafolide (EC145) and pegylated liposomal doxorubicin (PLD) in combination versus PLD alone in patients with platinum-resistant ovarian cancer. J Clin Oncol 31:4400–4406

    Article  CAS  PubMed  Google Scholar 

  29. Parker C, Nilsson S et al (2013) Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 369:213–223

    Article  CAS  PubMed  Google Scholar 

  30. Pujade-Lauraine E, Hilpert F et al (2014) Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol 32:1302–1308

    Article  CAS  PubMed  Google Scholar 

  31. Razzak M (2013) Gynaecological cancer: vintafolide – targeting the folate receptor with a cytotoxic offers hope. Nat Rev Clin Oncol 10:668

    Article  PubMed  Google Scholar 

  32. Reck M, Bondarenko I et al (2013) Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol 24:75–83

    Article  CAS  PubMed  Google Scholar 

  33. Reck M, Kaiser R et al (2014) Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. Lancet Oncol 15(2):143–155

    Article  CAS  PubMed  Google Scholar 

  34. Rosell R, Carcereny E et al (2012) Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol 13:239–246

    Article  CAS  PubMed  Google Scholar 

  35. Ryan CJ, Smith MR et al (2013) Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med 368:138–148

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Scher HI, Fizazi K et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187–1197

    Article  CAS  PubMed  Google Scholar 

  37. Schneeweiss A, Chia S et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24:2278–2284

    Article  CAS  PubMed  Google Scholar 

  38. Sekulic A, Migden MR et al (2012) Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N Engl J Med 366:2171–2179

    Article  CAS  PubMed  Google Scholar 

  39. Sequist LV, Yang JC et al (2013) Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol 31:3327–3334

    Article  CAS  PubMed  Google Scholar 

  40. Shaw AT, Kim DW et al (2014) Ceritinib in ALK-rearranged non-small-cell lung cancer. N Engl J Med 370:1189–1197

    Article  CAS  PubMed  Google Scholar 

  41. Shaw AT, Kim DW et al (2013) Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N Engl J Med 368:2385–2394

    Article  CAS  PubMed  Google Scholar 

  42. Stark D, Nankivell M et al (2013) Standard chemotherapy with or without bevacizumab in advanced ovarian cancer: quality-of-life outcomes from the International Collaboration on Ovarian Neoplasms (ICON7) phase 3 randomised trial. Lancet Oncol 14:236–243

    Article  PubMed Central  PubMed  Google Scholar 

  43. Tabernero J, Van Cutsem E et al (2013) Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer 50(2):320–331

    Article  PubMed  Google Scholar 

  44. Van Cutsem E, Haas S de et al (2012) Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a biomarker evaluation from the AVAGAST randomized phase III trial. J Clin Oncol 30:2119–2127

    Article  Google Scholar 

  45. Van Cutsem E, Tabernero J et al (2012) Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 30:3499–3506

    Article  Google Scholar 

  46. Verma S, Miles D et al (2012) Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 367:1783–1791

    Article  CAS  PubMed  Google Scholar 

  47. Von Hoff DD, Ervin T et al (2013) Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med 369(18):1691–1703

    Article  Google Scholar 

  48. Waddell T, Chau I et al (2013) Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol 14:481–489

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  49. Wolchok JD, Kluger H et al (2013) Nivolumab plus Ipilimumab in Advanced Melanoma. N Engl J Med 369:122–133

    Article  CAS  PubMed  Google Scholar 

  50. Wolchok JD, Weber JS et al (2013) Four-year survival rates for patients with metastatic melanoma who received ipilimumab in phase II clinical trials. Ann Oncol (E-pub ahead of print)

  51. Wu YL, Zhou C et al (2014) Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol 15:213–222

    Article  CAS  PubMed  Google Scholar 

Download references

Einhaltung ethischer Richtlinien

Interessenkonflikt. A. Stein hat im Rahmen von Vorträgen und Beratertätigkeiten Honorare von Roche, Merck, Bayer und Sanofi Aventis, sowie Erstattung von Reisekosten und Kongressgebühren von Bayer, Roche und Merck erhalten. C. Bokemeyer hat im Rahmen von Vorträgen und Beratertätigkeiten Honorare von Amgen, Roche, Merck, Bayer und Sanofi Aventis sowie Erstattung von Reisekosten und Kongressgebühren von Bayer, Roche und Merck erhalten. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Author information

Authors and Affiliations

  1. II. Medizinische Klinik und Poliklinik, Hubertus Wald Tumorzentrum, Universitäres Cancer Center Hamburg, Universitätsklinikum Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Deutschland

    A. Stein & C. Bokemeyer

Authors
  1. A. Stein
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Bokemeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A. Stein.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stein, A., Bokemeyer, C. Neue Substanzen für die Therapie solider Tumoren. Forum 29, 300–304 (2014). https://doi.org/10.1007/s12312-014-1160-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12312-014-1160-9

Schlüsselwörter

Keywords

Search

Navigation