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Die medikamentöse Therapie des kolorektalen Karzinoms

Chemotherapy of colorectal cancer

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Zusammenfassung

Das kolorektale Karzinom ist mit fast 30.000 Todesfällen pro Jahr hierzulande die zweithäufigste krebsbedingte Todesursache. Noch immer verstirbt fast jeder 2. Patient an der Erkrankung. Im letzten Jahrzehnt konnte durch die Einführung neuer, effektiver Chemotherapeutika und biologischer Substanzen die medikamentöse Therapie entscheidend verbessert werden. Beim Kolonkarzinom im Stadium III gilt eine adjuvante Kombinationstherapie mit Oxaliplatin als Standardtherapie. Im metastasierten Stadium ist für einen Teil der Patienten entweder durch eine primäre Resektion oder durch eine sekundäre Resektion der Metastasen nach neoadjuvanter Kombinationstherapie und Verkleinerung der Tumoren eine Heilung möglich. In der palliativen Therapie ist bei tumorbedingten Symptomen oder raschem Progress der Erkrankung eine intensive Kombinationstherapie indiziert. Das Therapieziel ist die Verlängerung des Überlebens bei akzeptabler Lebensqualität. Durch die Kombination mit zielgerichteten Substanzen wird eine weitere Verbesserung des Überlebens erreicht. Darüber hinaus wurde vor Kurzem mit dem Mutationsstatus des KRAS-Onkogens ein erster prädiktiver molekularer Marker in die klinische Praxis eingeführt, was einen entscheidenden ersten Schritt hin zu einer Individualisierung der Therapie beim kolorektalen Karzinom darstellt.

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer death in the western world. Almost every second patient dies of the disease. The introduction of new and effective chemotherapeutic substances and biologics in the past decade has significantly improved the systemic treatment of patients with CRC. In stage III colon cancer combination chemotherapy with oxaliplatin is the standard of care. In stage IV cancer the choice of therapy is dependent on the clinical status of the patient. For some patients primary resection of metastases or resection after combination therapy and downsizing of lesions offers a chance for cure. In the palliative setting intensive combination treatment is indicated if the patient suffers from tumor related symptoms or a rapid progress of the disease. The aim of palliative therapy is the prolongation of survival and the improvement of quality of life. Combination with monoclonal antibodies leads to further improvement of survival. Furthermore, the introduction of the mutational status of the KRAS oncogene as the first predictive marker into clinical care is an important step towards the individualization of treatment in CRC.

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Abbreviations

5-FU:

5-Fluorouracil

5-FU/FS:

5-Fluorouracil/Folinsäure

5-JÜR:

5-Jahres-Überlebensrate

ASCO:

American Society of Clinical Oncology

BICC:

„Bolus, Infusional or Capecitabine with Camptosar-Celecoxib“ Studie

BRAF:

Humanes Onkogen: V-raf murine sarcoma viral oncogene homolog B1

CAIRO:

„CApecitabine, IRinotecan, Oxaliplatin“ Studie

CASH:

Chemotherapie-assoziierte Steatohepatitis

CEA:

Karzinoembryonales Antigen

CELIM:

„CEtuximab in neoadjuvant treatment of non-resectable colorectal LIver Metastases“ Studie

CRC:

Colorectal cancer

CPT-11:

Irinotecan

CRYSTAL:

„Cetuximab combined with iRinotecan in first line therapY for metaSTatic colorectAL cancer“ Studie

DFS:

Erkrankungsfreies Überleben

DTZ:

Disseminierte Tumorzellen

EGFR:

Epidermal Growth Factor Receptor

EORTC:

European Organisation for Research and Treatment of Cancer

FOLFIRI:

Kombinationschemotherapie mit Irinotecan, 5-FU und Folinsäure

FOLFOX:

Kombinationschemotherapie mit Oxaliplatin, 5-FU und Folinsäure

HAI:

Hepatic Artery Infusion

HES:

Hyperexzitabilitätssyndrom

HR:

Hazard Ratio

IGF-1R:

Insulin-like Growth Factor 1 Receptor

KRK:

Kolorektales Karzinom

KRAS:

Kirsten rat sarcoma viral homolog Oncogen

MOSAIC:

„Multi-center international study of oxaliplatin/5-fluorouracil/leucovorin in the adjuvant treatment of colon cancer“ Studie

MTOR:

Mammalian Target of Rapamycin

NSABP:

National Surgical Adjuvant Breast and Bowel Project Studiengruppe

OS:

Gesamtüberleben

PETACC:

Pan-European Trials in Adjuvant Colon Cancer Studiengruppe

PFS:

Progressionsfreies Überleben

PSN:

Periphere sensible Neuropathie

RECIST:

Response Evaluation Criteria In Solid Tumors, Kriterien zur Evaluierung des Therapieansprechens bei soliden Tumoren

SOS:

Sinusoidales Obstruktionssyndrom

TNM:

Tumorklassifikation nach der UICC (6. Auflage, 2002)

UICC:

Union internationale contre le cancer (UICC)

VEGF:

Vascular Endothelial Growth Factor

X-Act:

„Xeloda in Adjuvant Colon Cancer Therapy“ Studie

XELOX:

Kombinationschemotherapie mit Capecitabin und Oxaliplatin

XELIRI:

Kombinationschemotherapie mit Capecitabin und Irinotecan, Synonym CapIri

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Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin:

Prof. Dr. Schmiegel ist als Referent und gegen Beraterhonorar für die Firmen Astra-Zeneca, Roche, and Sanofi-Aventis tätig, PD Dr. Reinacher-Schick als Referent und gegen Beraterhonorar für die Firmen Amgen, Roche and Sanofi-Aventis, Dr. Pohl als Referent für die Firmen Roche und Amgen.

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Reinacher-Schick, A., Pohl, M. & Schmiegel, W. Die medikamentöse Therapie des kolorektalen Karzinoms. Internist 50, 1239–1252 (2009). https://doi.org/10.1007/s00108-009-2508-6

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