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Strahlentherapie und Onkologie

, Volume 185, Issue 6, pp 371–378 | Cite as

Molecular targeted treatment and radiation therapy for rectal cancer

  • Friederike Marquardt
  • Franz Rödel
  • Gianni Capalbo
  • Christian Weiss
  • Claus Rödel
Original Article

Background:

EGFR (epidermal growth factor receptor) and VEGF (vascular endothelial growth factor) inhibitors confer clinical benefit in metastatic colorectal cancer when combined with chemotherapy. An emerging strategy to improve outcomes in rectal cancer is to integrate biologically active, targeted agents as triple therapy into chemoradiation protocols.

Material and Methods:

Cetuximab and bevacizumab have now been incorporated into phase I–II studies of preoperative chemoradiation therapy (CRT) for rectal cancer. The rationale of these combinations, early efficacy and toxicity data, and possible molecular predictors for tumor response are reviewed. Computerized bibliographic searches of Pubmed were supplemented with hand searches of reference lists and abstracts of ASCO and ASTRO meetings.

Results:

The combination of cetuximab and CRT can be safely applied without dose compromises of the respective treatment components. Disappointingly low rates of pathologic complete remission have been noted in several phase II studies. The K-ras mutation status and the gene copy number of EGFR may predict tumor response. The toxicity pattern (radiation-induced enteritis, perforations) and surgical complications (wound healing, fistula, bleeding) observed in at least some of the clinical studies with bevacizumab and CRT warrant further investigations.

Conclusion:

Longer follow-up (and, finally, randomized trials) is needed to draw any firm conclusions with respect to local and distant failure rates, and toxicity associated with these novel treatment approaches.

Key Words:

Cetuximab Bevacizumab Chemoradiotherapy Rectal cancer 

Molekular-zielgerichtete Therapie und Bestrahlung zur Behandlung des Rektumkarzinoms

Hintergrund:

EGFR-(epidermaler Wachstumsfaktor-Rezeptor) und VEGF-Inhibitoren (vaskulärer endothelialer Wachstumsfaktor) zeigen beim metastasierten kolorektalen Karzinom in Kombination mit Chemotherapie einen klinischen Vorteil. Diese biologisch aktiven, zielgerichteten Substanzen werden als Dreifachtherapie zunehmend auch bei der Radiochemotherapie des Rektumkarzinoms eingesetzt.

Material und Methodik:

Cetuximab und Bevacizumab sind in Phase-I–II-Studien zur präoperativen Radiochemotherapie des Rektumkarzinoms getestet worden. Die Rationale für diese Kombination, erste Wirksamkeits- und Toxizitätsdaten sowie mögliche molekulare Responsemarker werden dargestellt. Dazu diente eine Suchabfrage in Pubmed, in Referenzlisten publizierter Arbeiten sowie Abstracts von ASCO- und ASTRO-Konferenzen.

Ergebnisse:

Cetuximab und Radiochemotherapie können ohne Dosiskompromisse sicher miteinander kombiniert werden. Zahlreiche Phase-II-Studien ergaben allerdings enttäuschende Raten an pathologisch bestätigten kompletten Remissionen. Der K-ras-Mutationsstatus und die Anzahl an Genkopien des EGFR scheinen die Tumorantwort zu prädizieren. Das bei Kombination von Bevacizumab mit einer Radiochemotherapie beobachtete Toxizitätsspektrum (Enteritis, Perforationen) sowie die postoperativen Komplikationen (Wundheilungsstörungen, Fistelbildung, Blutungen) erfordern weitere Untersuchungen.

Schlussfolgerung:

Längere Nachbeobachtungszeiten (und schließlich randomisierte Studien) sind nötig, um Daten zu Lokalrezidiv- und Fernmetastasenraten sowie zur Toxizität dieser Kombinationstherapien zu erhalten.

Schlüsselwörter:

Cetuximab Bevacizumab Radiochemotherapie Rektumkarzinom 

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Copyright information

© Urban & Vogel, Muenchen 2009

Authors and Affiliations

  • Friederike Marquardt
  • Franz Rödel
  • Gianni Capalbo
  • Christian Weiss
  • Claus Rödel
    • 1
    • 2
  1. 1.Department of Radiation TherapyUniversity of Frankfurt/MainFrankfurt/MainGermany
  2. 2.Klinik für Strahlentherapie und OnkologieGoethe-Universität Frankfurt/MainFrankfurt/MainGermany

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