Der Internist

, Volume 55, Issue 1, pp 37–42 | Cite as

Chemotherapie des metastasierten kolorektalen Karzinoms

Schwerpunkt

Zusammenfassung

Zur systemischen Therapie des metastasierten kolorektalen Karzinoms (mKRK) stehen zunehmend mehr Optionen zur Verfügung, die eine sorgfältige Therapieplanung bereits vor Therapiestart notwendig machen. Die Wahl der Erstlinientherapie richtet sich nach klinischen und molekularpathologischen Parametern, z. B. nach Mutationen der (K-)RAS-Gene bezüglich der Therapiesteuerung von Epidermal-growth-factor-receptor(EGFR)-Antikörpern. Die Erstlinientherapie beeinflusst alle weiteren therapeutischen Entscheidungen und kann daher als Weichenstellung bezeichnet werden. Kombinationen aus Chemotherapie und Biologika sind derzeit der Therapiestandard. Dabei mehren sich in der Erstlinientherapie die Hinweise, dass Patienten mit (K-)RAS-Wildtyp-Tumoren hinsichtlich des Gesamtüberlebens von einer primären Anti-EGFR-Therapie mehr als von einer Anti-vascular-endothelial-growth-factor(VEGF)-Strategie profitieren. Die Entwicklung wirkungsvoller Therapiestrategien für Patienten mit (K-)RAS-mutiertem mKRK – das sind etwa 50 % aller Patienten – muss in der Zukunft vorangetrieben werden, da die therapeutischen Optionen für diese Gruppe von Patienten deutlich limitiert sind.

Schlüsselwörter

Gene, RAS Epidermal-growth-factor-receptor-Antikörper Irinotecan Capecitabin Personalisierte Medizin 

Chemotherapy of metastatic colorectal cancer

Abstract

Increasing numbers of therapeutic options are becoming available for the systemic treatment of metastasized colorectal cancer (mCRC) which emphasizes the need for strategic decision making and planning across multiple lines of treatment. The choice of first-line therapy is influenced by clinical and molecular characteristics of patients and tumors, such as (K-)RAS gene mutations with respect to therapy guidance of epidermal growth factor receptor (EGFR) antibodies. First-line therapy is the major determinant of subsequent treatment regimens and can therefore be considered as the key decision in patients with mCRC. The German standard for first-line therapy in the majority of patients includes chemotherapy in combination with biological agents, with antibodies targeting EGFR possibly being the preferable option in patients with (K-)RAS wild-type tumors. The development of effective therapeutic strategies in patients with (K-)RAS mutant mCRC tumors must be promoted in the future and requires intensive research because the therapy options for this group of patients are very limited.

Keywords

Genes, RAS Epidermal growth factor receptor antibodies Irinotecan Capecitabine Personalized medicine 

Notes

Einhaltung ethischer Richtlinien

Interessenkonflikt. D.P. Modest: Forschungsunterstützung, Reiseunterstützung und Vortragshonorare: Amgen, Merck Serono und Roche. W. Hiddemann gibt an, dass kein Interessenkonflikt besteht. V. Heinemann: Forschungsunterstützung, Reiseunterstützung, Vortragshonorare und Beratungstätigkeit: Amgen, Merck Serono, Roche, Sanofi-Aventis. Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.

Literatur

  1. 1.
    Robert-Koch-Institut, Zentrum für Krebsregisterdaten. http://www.krebsdaten.de/Krebs/DE/Content/Krebsarten/Darmkrebs/Google Scholar
  2. 2.
    Haas RJ de, Wicherts DA, Flores E et al (2008) R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg 248:626–637PubMedGoogle Scholar
  3. 3.
    Schmoll HJ, Cutsem E van, Stein A et al (2012) ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making. Ann Oncol 23:2479–2516PubMedCrossRefGoogle Scholar
  4. 4.
    Heinemann V, Weikersthal L von, Decker T et al (2013) Randomized comparison of FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment of KRAS wild-type metastatic colorectal cancer: German AIO study KRK-0306 (FIRE-3). J Clin Oncol 31 (Suppl):Abstract LBA3506Google Scholar
  5. 5.
    Stintzing S, Jung A, Rossius L et al (2013) Analysis of KRAS/NRAS and BRAF mutations in FIRE-3: a randomized phase III study of FOLFIRI plus cetuximab or bevacizumab as first-line treatment for wild-type (WT) KRAS (exon 2) metastatic colorectal cancer (mCRC) patients. ECCO/ESMO 2013, LBA17Google Scholar
  6. 6.
    Van Cutsem E, Köhne CH, Lang I et al (2011) Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol 29:2011–2019Google Scholar
  7. 7.
    Douillard JY, Oliner KS, Siena S et al (2013) Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 369:1023–1034Google Scholar
  8. 8.
    Falcone A, Cremolini C, Masi G et al (2013) FOLFOXIRI/bevacizumab (bev) versus FOLFIRI/bev as first-line treatment in unresectable metastatic colorectal cancer (mCRC) patients (pts): results of the phase III TRIBE trial by GONO group. J Clin Oncol 31 (Suppl):Abstract 3505Google Scholar
  9. 9.
    Saltz LB, Clarke S, Díaz-Rubio E et al (2008) Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol 26:2013–2019Google Scholar
  10. 10.
    Amado RG, Wolf M, Peeters M et al (2008) Wild-type KRAS is required for panitumumab efficacy in patients with metastatic colorectal cancer. J Clin Oncol 26:1626–1634Google Scholar
  11. 11.
    Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342Google Scholar
  12. 12.
    Bennouna J, Sastre J, Arnold D et al (2012) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14:29–37PubMedCrossRefGoogle Scholar
  13. 13.
    Van Cutsem E, Tabernero J, Lakomy R 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 30:3499–3506Google Scholar
  14. 14.
    Peeters M, Price TJ, Cervantes A et al (2010) Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol 28:4706–4713Google Scholar
  15. 15.
    Giantonio BJ, Catalano PJ, Meropol NJ et al (2007) Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 25:1539–1544Google Scholar
  16. 16.
    Cunningham D, Humblet Y, Siena S et al (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345Google Scholar
  17. 17.
    Karapetis CS, Khambata-Ford S, Jonker DJ et al (2008) K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med 359:1757–1765Google Scholar
  18. 18.
    Santini D, Vincenzi B, Addeo R et al (2012) Cetuximab rechallenge in metastatic colorectal cancer patients: how to come away from acquired resistance? Ann Oncol 23:2313–2318PubMedCrossRefGoogle Scholar
  19. 19.
    Grothey A, Van Cutsem E, Sobrero A et al (2013) Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381:303–312PubMedCrossRefGoogle Scholar
  20. 20.
    Nordlinger B, Sorbye H, Glimelius B et al (2013) Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol 14:1208–1215PubMedCrossRefGoogle Scholar
  21. 21.
    Mitry E, Fields AL, Bleiberg H et al (2008) Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol 26:4906–4911Google Scholar
  22. 22.
    Kabbinavar FF, Schulz J, McCleod M et al (2005) Addition of bevacizumab to bolus fluorouracil and leucovorin in first-line metastatic colorectal cancer: results of a randomized phase II trial. J Clin Oncol 23:3697–3705Google Scholar
  23. 23.
    Cunningham D, Lang I, Marcuello E et al (2013) Bevacizumab (bev) in combination with capecitabine (cape) for the first-line treatment of elderly patients with metastatic colorectal cancer (mCRC): results of a randomized international phase III trial (AVEX). Lancet Oncol 14:1077–1085PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Medizinische Klinik und Poliklinik III & Comprehensive Cancer CenterKlinikum der Universität MünchenMünchenDeutschland

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