Skip to main content
main-content

Tipp

Weitere Artikel dieser Ausgabe durch Wischen aufrufen

Erschienen in: Wiener klinisches Magazin 2/2015

01.04.2015 | Onkologie

Systemtherapie des metastasierten kolorektalen Karzinoms

verfasst von: Prof. Dr. Stefan Kubicka

Erschienen in: Wiener klinisches Magazin | Ausgabe 2/2015

Einloggen, um Zugang zu erhalten
share
TEILEN

Zusammenfassung

Hintergrund

Die Systemtherapie des metastasierten kolorektalen Karzinoms soll eine möglichst lange Lebenszeit bei guter Lebensqualität der Patienten gewährleisten. Hierbei wird das Konzept der streng abgegrenzten Therapielinien immer mehr verlassen und stattdessen durch eine individuelle Therapieplanung ersetzt, welche auch Erhaltungstherapien einschließt und sich nach der Tumorausbreitung und Tumorbiologie, dem klinischen Zustand des Patienten sowie den auftretenden Nebenwirkungen ausrichtet.

Methode

Literaturrecherche und Auswertung klinischer Studien.

Ergebnisse und Schlussfolgerungen

Da die Erstlinien-Kombinationschemotherapie mit einem Anti-EGFR-Antikörper von kolorektalen RAS-Wild-Typ(wt)-Karzinomen (K- und NRAS Exon 2, 3 und 4) mit einem signifikanten Überlebensvorteil für die Patienten verbunden sein könnte, sollte bei allen Patienten, für die eine intensive Erstlinien-Kombinationschemotherapie in Frage kommt, der komplette RAS-Status vor Therapiebeginn bestimmt werden. Um den Patienten potenzielle Heilungschancen oder auch längere systemtherapiefreie Intervalle zu geben, ist es essenziell, dass bei limitierter Leber- und/oder Lungenmetastasierung die vollständige Entfernung des Tumors durch einen chirurgischen Eingriff und/oder lokale Tumorablation im Auge behalten wird, auch wenn diese nur durch eine Konversion nach einer intensiven Induktionschemotherapie möglich erscheint. Hierfür ist eine enge Abstimmung mit einem ausgewiesenen Chirurgen im Rahmen von interdisziplinären Tumorkonferenzen vor und im Verlauf der Systemtherapie notwendig.
Literatur
1.
Zurück zum Zitat 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(10):1626–1634 CrossRefPubMed 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(10):1626–1634 CrossRefPubMed
2.
Zurück zum Zitat Bennouna J, Sastre J, Arnold D et al (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14(1):29–37 CrossRefPubMed Bennouna J, Sastre J, Arnold D et al (2013) Continuation of bevacizumab after first progression in metastatic colorectal cancer (ML18147): a randomised phase 3 trial. Lancet Oncol 14(1):29–37 CrossRefPubMed
3.
Zurück zum Zitat Bokemeyer C, Bondarenko I, Makhson A et al (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27(5):663–671 CrossRefPubMed Bokemeyer C, Bondarenko I, Makhson A et al (2009) Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer. J Clin Oncol 27(5):663–671 CrossRefPubMed
4.
Zurück zum Zitat Chibaudel B, Maindrault-Goebel F, Lledo G et al (2009) Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 Study. J Clin Oncol 27(34):5727–5733 CrossRefPubMed Chibaudel B, Maindrault-Goebel F, Lledo G et al (2009) Can chemotherapy be discontinued in unresectable metastatic colorectal cancer? The GERCOR OPTIMOX2 Study. J Clin Oncol 27(34):5727–5733 CrossRefPubMed
5.
Zurück zum Zitat Cunningham D, Lang I, Marcuello E et al (2013) Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 14(11):1077–1085 CrossRefPubMed Cunningham D, Lang I, Marcuello E et al (2013) Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial. Lancet Oncol 14(11):1077–1085 CrossRefPubMed
6.
Zurück zum Zitat Douillard JY, Oliner KS, Siena S et al (2013) Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 369(11):1023–1034 CrossRefPubMed Douillard JY, Oliner KS, Siena S et al (2013) Panitumumab-FOLFOX4 treatment and RAS mutations in colorectal cancer. N Engl J Med 369(11):1023–1034 CrossRefPubMed
7.
Zurück zum Zitat Douillard JY, Siena S, Cassidy J et al (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28:4697–4705 CrossRefPubMed Douillard JY, Siena S, Cassidy J et al (2010) Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol 28:4697–4705 CrossRefPubMed
8.
Zurück zum Zitat 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; abstr 3505) 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; abstr 3505)
9.
Zurück zum Zitat Falcone A, Ricci S, Brunetti I et al (2007) Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 25(13):1670–1676 CrossRefPubMed Falcone A, Ricci S, Brunetti I et al (2007) Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol 25(13):1670–1676 CrossRefPubMed
10.
Zurück zum Zitat Folprecht G, Gruenberger T, Bechstein WO et al (2010) Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol 11(1):38–47 CrossRefPubMed Folprecht G, Gruenberger T, Bechstein WO et al (2010) Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial. Lancet Oncol 11(1):38–47 CrossRefPubMed
11.
Zurück zum Zitat 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(12):1539–1544 CrossRefPubMed 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(12):1539–1544 CrossRefPubMed
12.
Zurück zum Zitat 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(9863):303–312 CrossRefPubMed 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(9863):303–312 CrossRefPubMed
13.
Zurück zum Zitat Hecht JR, Cohn AL, Dakhil SR et al (2013) SPIRITT (study 20060141): a randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC). J Clin Oncol 31(suppl 4; abstr 454) Hecht JR, Cohn AL, Dakhil SR et al (2013) SPIRITT (study 20060141): a randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC). J Clin Oncol 31(suppl 4; abstr 454)
14.
Zurück zum Zitat Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342 CrossRefPubMed Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350(23):2335–2342 CrossRefPubMed
15.
Zurück zum Zitat 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(17):1757–1765 CrossRefPubMed 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(17):1757–1765 CrossRefPubMed
16.
Zurück zum Zitat Koopman M, Simkens L, May A et al (2014) Final results and subgroup analyses of the phase 3 CAIRO3 study: maintenance treatment with capecitabine and bevacizumab versus observation after induction treatment with chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC). J Clin Oncol 32(suppl 3; abstr LBA388) Koopman M, Simkens L, May A et al (2014) Final results and subgroup analyses of the phase 3 CAIRO3 study: maintenance treatment with capecitabine and bevacizumab versus observation after induction treatment with chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC). J Clin Oncol 32(suppl 3; abstr LBA388)
17.
Zurück zum Zitat Masi G, Loupakis F, Salvatore L et al. (2013) Second-line chemotherapy (CT) with or without bevacizumab (BV) in metastatic colorectal cancer (mCRC) patients (pts) who progressed to a first-line treatment containing BV: Updated results of the phase III „BEBYP“ trial by the Gruppo Oncologico Nord Ovest (GONO). J Clin Oncol 31 (suppl; abstr 3615) Masi G, Loupakis F, Salvatore L et al. (2013) Second-line chemotherapy (CT) with or without bevacizumab (BV) in metastatic colorectal cancer (mCRC) patients (pts) who progressed to a first-line treatment containing BV: Updated results of the phase III „BEBYP“ trial by the Gruppo Oncologico Nord Ovest (GONO). J Clin Oncol 31 (suppl; abstr 3615)
18.
Zurück zum Zitat Maughan TS, Adams RA, Smith CG et al (2011) Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 377(9783):2103–2114 CrossRefPubMedCentralPubMed Maughan TS, Adams RA, Smith CG et al (2011) Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial. Lancet 377(9783):2103–2114 CrossRefPubMedCentralPubMed
19.
Zurück zum Zitat 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(31):4706–4713 CrossRefPubMed 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(31):4706–4713 CrossRefPubMed
20.
Zurück zum Zitat 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(12):2013–2019 CrossRefPubMed 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(12):2013–2019 CrossRefPubMed
21.
Zurück zum Zitat Schwartzberg LS, Rivera F, Karthaus M et al (2014) PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol (Epub ahead of print) Schwartzberg LS, Rivera F, Karthaus M et al (2014) PEAK: a randomized, multicenter phase II study of panitumumab plus modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or bevacizumab plus mFOLFOX6 in patients with previously untreated, unresectable, wild-type KRAS exon 2 metastatic colorectal cancer. J Clin Oncol (Epub ahead of print)
22.
Zurück zum Zitat Seymour MT, Brown SR, Middleton G et al (2013) Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol 14(8):749–759 CrossRefPubMedCentralPubMed Seymour MT, Brown SR, Middleton G et al (2013) Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial. Lancet Oncol 14(8):749–759 CrossRefPubMedCentralPubMed
23.
Zurück zum Zitat Seymour MT, Thompson LC, Wasan HS et al (2011) Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet 377(9779):1749–1759 CrossRefPubMedCentralPubMed Seymour MT, Thompson LC, Wasan HS et al (2011) Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial. Lancet 377(9779):1749–1759 CrossRefPubMedCentralPubMed
24.
Zurück zum Zitat Shindoh J, Loyer EM, Kopetz S et al (2012) Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases. J Clin Oncol 30(36):4566–4572 CrossRefPubMedCentralPubMed Shindoh J, Loyer EM, Kopetz S et al (2012) Optimal morphologic response to preoperative chemotherapy: an alternate outcome end point before resection of hepatic colorectal metastases. J Clin Oncol 30(36):4566–4572 CrossRefPubMedCentralPubMed
25.
Zurück zum Zitat Sobrero AF, Maurel J, Fehrenbacher L et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26(14):2311–2319 CrossRefPubMed Sobrero AF, Maurel J, Fehrenbacher L et al (2008) EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol 26(14):2311–2319 CrossRefPubMed
26.
Zurück zum Zitat Souglakos J, Androulakis N, Syrigos K et al (2006) FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicenter randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer 94:798–805 CrossRefPubMedCentralPubMed Souglakos J, Androulakis N, Syrigos K et al (2006) FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) vs FOLFIRI (folinic acid, 5-fluorouracil and irinotecan) as first-line treatment in metastatic colorectal cancer (MCC): a multicenter randomised phase III trial from the Hellenic Oncology Research Group (HORG). Br J Cancer 94:798–805 CrossRefPubMedCentralPubMed
27.
Zurück zum Zitat 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. Eur J Cancer 49(suppl 3):s8 abstract LBA17 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. Eur J Cancer 49(suppl 3):s8 abstract LBA17
28.
Zurück zum Zitat Tournigand C, Cervantes A, Figer A et al (2006) OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer – a GERCOR study. J Clin Oncol 24(3):394–400 CrossRefPubMed Tournigand C, Cervantes A, Figer A et al (2006) OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer – a GERCOR study. J Clin Oncol 24(3):394–400 CrossRefPubMed
29.
Zurück zum Zitat Tveit KM, Guren T, Glimelius B et al (2012) Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 30(15):1755–1762 CrossRefPubMed Tveit KM, Guren T, Glimelius B et al (2012) Phase III trial of cetuximab with continuous or intermittent fluorouracil, leucovorin, and oxaliplatin (Nordic FLOX) versus FLOX alone in first-line treatment of metastatic colorectal cancer: the NORDIC-VII study. J Clin Oncol 30(15):1755–1762 CrossRefPubMed
30.
Zurück zum Zitat Van Cutsem E, Köhne CH, Láng 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(15):2011–2019 CrossRefPubMed Van Cutsem E, Köhne CH, Láng 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(15):2011–2019 CrossRefPubMed
31.
Zurück zum Zitat 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(28):3499–3506 CrossRefPubMed 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(28):3499–3506 CrossRefPubMed
32.
Zurück zum Zitat Ye LC, Liu TS, Ren L et al (2013) Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol 31(16):1931–1938 CrossRefPubMed Ye LC, Liu TS, Ren L et al (2013) Randomized controlled trial of cetuximab plus chemotherapy for patients with KRAS wild-type unresectable colorectal liver-limited metastases. J Clin Oncol 31(16):1931–1938 CrossRefPubMed
Metadaten
Titel
Systemtherapie des metastasierten kolorektalen Karzinoms
verfasst von
Prof. Dr. Stefan Kubicka
Publikationsdatum
01.04.2015
Verlag
Springer Vienna
Erschienen in
Wiener klinisches Magazin / Ausgabe 2/2015
Print ISSN: 1869-1757
Elektronische ISSN: 1613-7817
DOI
https://doi.org/10.1007/s00740-015-0042-9

Weitere Artikel der Ausgabe 2/2015

Wiener klinisches Magazin 2/2015 Zur Ausgabe

Panorama

Panorama