Der Gastroenterologe

, Volume 7, Issue 1, pp 14–23

Risikoadaptierte adjuvante Therapie des Kolonkarzinoms

Schwerpunkt
  • 79 Downloads

Zusammenfassung

Die adjuvante Therapie von Patienten mit einem Kolonkarzinom erfolgt gemäß bestimmten Risikogruppen. Im UICC-Stadium III ist die adjuvante Therapie mit einer oxaliplatinhaltigen Chemotherapie (Folfox oder Capox) indiziert (Empfehlungsgrad A). Bei Patienten, die keine Kombinationschemotherapie erhalten können, sollte Capecitabin als Monosubstanz eingesetzt werden. Bei Patienten im Stadium II entscheiden weiterhin die bekannten klinischen und pathologischen Risikofaktoren wie T4-Kategorie, zu wenige untersuchte Lymphknoten, Notfalloperation oder Tumoreinriss/-perforation über die Indikation für eine adjuvante Chemotherapie. Liegen solche Risikofaktoren vor, so sollte eine adjuvante Therapie mit einem Fluoropyrimidin eingeleitet werden. Keiner dieser Risikofaktoren ist bislang prospektiv validiert. Oxaliplatin hat im Stadium II keinen Stellenwert, da der absolute Überlebensbenefit gering ist. Für Patienten ohne klinische Risikofaktoren besteht eine „Kann“-Empfehlung für eine adjuvante Therapie auf dem Boden der QUASAR-Studie. Die US-amerikanischen Empfehlungen sehen hingegen keine Indikation für eine adjuvante Therapie im Stadium II ohne Risikofaktoren.

Schlüsselwörter

Kolonkarzinom Risikofaktoren Kombinationschemotherapie 5-FU-Monotherapie Molekulare Marker 

Risk-adapted adjuvant treatment of colon cancer

Abstract

Adjuvant treatment of colon cancer is recommended according to the initial UICC stage of the disease and certain risk factors. If lymph nodes are afflicted (UICC stage III) combination chemotherapy with oxaliplatin and fluoropyrimidines (5-FU or capecitabine) should be administered (evidence level 1a, recommendation level A) following data from the French MOSAIC study. If patients do not qualify for combination treatment monotherapy with fluoropyrimidines should be given preferably with capecitabine. In UICC stage II cancer the recommendation for adjuvant therapy depends on the presence of certain risk factors such as T4 category, emergency surgery, perforation and insufficient lymph nodes examined (less than 12), and patients should then receive adjuvant chemotherapy with fluoropyrimidines. However, none of these risk factors have been validated prospectively and the predictive value is unclear. Oxaliplatin should not be added in stage II cancer. If patients are diagnosed with stage II cancer without risk factors then fluoropyrimidines may be given according to the results of the QUASAR study. In contrast, the ASCO guidelines do not recommend chemotherapy for stage II patients without risk factors.

Keywords

Colonic neoplasms Risk factors Combination chemotherapy 5-Fluorouracil monotherapy Molecular markers 

Literatur

  1. 1.
    Alberts SR, Sargent DJ, Smyrk TC et al (2010) Adjuvant mFOLFOX6 with or without cetuxiumab (Cmab) in KRAS wild-type (WT) patients (pts) with resected stage III colon cancer (CC): results from NCCTG Intergroup Phase III Trial N0147. J Clin Oncol 28 (Suppl 18): A-CRA3507 (Abstract)CrossRefGoogle Scholar
  2. 2.
    Allegra CJ, Yothers G, O’Connell MJ et al (2011) Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol 29: 11–16PubMedCrossRefGoogle Scholar
  3. 3.
    André T, Boni C, Navarro M et al (2009) Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol 27: 3109–3116PubMedCrossRefGoogle Scholar
  4. 4.
    Benson AB III, Ajani JA, Catalano RB et al (2004) Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 22: 2918–2926PubMedCrossRefGoogle Scholar
  5. 5.
    Biagi JJ, Raphael MJ, Mackillop WJ et al (2011) Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis. JAMA 305: 2335–2342PubMedCrossRefGoogle Scholar
  6. 6.
    De Gramont A, Van Cutsem E, Tabernero J et al (2011) Results from a randomized, three-arm multinational phase III study to investigate bevacizumab with either XELOX or FOLFOX4 versus FOLFOX4 alone as adjuvant treatment for colon cancer. J Clin Oncol 29 (Suppl 4): Abstr 362Google Scholar
  7. 7.
    Gill S, Loprinzi CL, Sargent DJ et al (2004) Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: who benefits and by how much? J Clin Oncol 22: 1797–1806PubMedCrossRefGoogle Scholar
  8. 8.
    Haller DG, Tabernero J, Maroun J et al (2011) Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 29: 1465–1471PubMedCrossRefGoogle Scholar
  9. 9.
    Hutchins G, Southward K, Handley K et al (2011) Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 29: 1261–1270PubMedCrossRefGoogle Scholar
  10. 10.
    Jover R, Nguyen TP, Pérez-Carbonell L et al (2011) 5-Fluorouracil adjuvant chemotherapy does not increase survival in patients with CpG island methylator phenotype colorectal cancer. Gastroenterology 140: 1174–1181PubMedCrossRefGoogle Scholar
  11. 11.
    Kerr D, Gray R, Quirke P et al (2009) A quantitative multigene RT-PCR assay for prediction of recurrence in stage II colon cancer: Selection of the genes in four large studies and results of the independent, prospectively designed QUASAR validation study. J Clin Oncol 27 (Suppl): 15s (Abstr 4000)CrossRefGoogle Scholar
  12. 12.
    Martínez-López E, Abad A, Font A et al (1998) Allelic loss on chromosome 18q as a prognostic marker in stage II colorectal cancer. Gastroenterology 114: 1180–1187PubMedCrossRefGoogle Scholar
  13. 13.
    Merkel S, Wein A, Günther K et al (2001) High-risk groups of patients with Stage II colon carcinoma. Cancer 92: 1435–1443PubMedCrossRefGoogle Scholar
  14. 14.
    Morris M, Platell C, Boer B de et al (2006) Population-based study of prognostic factors in stage II colonic cancer. Br J Surg 93: 866–871PubMedCrossRefGoogle Scholar
  15. 15.
    O’Connell JB, Maggard MA, Ko CY (2004) Colon cancer survival rates with the new american joint committee on cancer sixth edition staging. J Natl Cancer Inst 96: 1420–1425CrossRefGoogle Scholar
  16. 16.
    O’Connell MJ, Lavery I, Yothers G et al (2010) Relationship between tumor gene expression and recurrence in four independent studies of patients with stage II/III colon cancer treated with surgery alone or surgery plus adjuvant fluorouracil plus leucovorin. J Clin Oncol 28: 3937–3944CrossRefGoogle Scholar
  17. 17.
    O’Connor ES, Greenblatt DY, LoConte NK et al (2011) Adjuvant chemotherapy for stage ii colon cancer with poor prognostic features. J Clin Oncol 29: 3381–3388CrossRefGoogle Scholar
  18. 18.
    Ogino S, Nosho K, Kirkner GJ et al (2009) CpG island methylator phenotype, microsatellite instability, BRAF mutation and clinical outcome in colon cancer. GUT 58: 90–96PubMedCrossRefGoogle Scholar
  19. 19.
    Petersen VC, Baxter KJ, Love SB, Shepherd NA (2002) Identification of objective pathological prognostic determinants and models of prognosis in Dukes‘ B colon cancer. GUT 51: 65–69PubMedCrossRefGoogle Scholar
  20. 20.
    QUASAR Collaborative Group (2007) Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet 370 (9604): 2020–2029CrossRefGoogle Scholar
  21. 21.
    Ribic CM, Sargent DJ, Moore MJ et al (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349: 247–257PubMedCrossRefGoogle Scholar
  22. 22.
    Rosenberg R, Maak M, Simon I et al (2011) Independent validation of a prognostic genomic profile (ColoPrint) for stage II colon cancer (CC) patients. J Clin Oncol 29 (Suppl 4): Abstr 358CrossRefGoogle Scholar
  23. 23.
    Salazar R, Roepman P, Capella G et al (2011) Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer. J Clin Oncol 29: 17–24PubMedCrossRefGoogle Scholar
  24. 24.
    Sargent DJ, Marsoni S, Thibodeau N et al (2008) Confirmation of deficient mismatch repair (dMMR) as a predictive marker for lack of benefit from 5-FU based chemotherapy in stage II and III colon cancer (CC): a pooled molecular reanalysis of randomized chemotherapy trials. J Clin Oncol 26 (Suppl): Abstr 4008CrossRefGoogle Scholar
  25. 25.
    Schmiegel W, Pox C, Arnold D et al (2009) Colorectal carcinoma: the management of polyps, (neo)adjuvant therapy, and the treatment of metastases. Dtsch Ärztebl Int 106(51–52): 843–848Google Scholar
  26. 26.
    Schmiegel W, Reinacher-Schick A, Arnold D et al (2008) Update S3-guideline „colorectal cancer“ 2008. Z Gastroenterol 46: 799–840PubMedCrossRefGoogle Scholar
  27. 27.
    Sinicrope FA, Foster NR, Thibodeau SN et al (2011) DNA mismatch repair status and colon cancer recurrence and survival in clinical trials of 5-fluorouracil-based adjuvant therapy. J Natl Cancer Inst 103: 863–875PubMedCrossRefGoogle Scholar
  28. 28.
    Teixeira L, Hickish T, Tournigand C et al (2010) Efficacy of FOLFOX4 as adjuvant therapy in stage II colon cancer (CC): A new analysis of the MOSAIC trial according to risk factors. J Clin Oncol 28: 15S(Suppl 3524)Google Scholar
  29. 29.
    Tejpar S (2010) Adjuvant chemotherapy for stage ii colon cancer: Are we closer to finding the patients who benefit? In: ASCO 2010 Educational BookGoogle Scholar
  30. 30.
    Tejpar S, Bosman F, Delorenzi M et al (2009) Microsatellite instability (MSI) in stage II and III colon cancer treated with 5FU-LV or 5FU-LV and irinotecan (PETACC 3-EORTC 40993-SAKK 60/00 trial). J Clin Oncol 27: 15S (Abstr 4001)CrossRefGoogle Scholar
  31. 31.
    Twelves C, Wong A, Nowacki MP et al (2005) Capecitabine as Adjuvant Treatment for Stage III Colon Cancer. N Engl J Med 352: 2696–2704PubMedCrossRefGoogle Scholar
  32. 32.
    Van Cutsem E, Labianca R, Bodoky G et al (2009) Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage iii colon cancer: petacc-3. J Clin Oncol 27: 3117–3125CrossRefGoogle Scholar
  33. 33.
    Walther A, Johnstone E, Swanton C et al (2009) Genetic prognostic and predictive markers in colorectal cancer. Nat Rev Cancer 9: 489–499PubMedCrossRefGoogle Scholar
  34. 34.
    Wittekind C, Meyer HJ (Hrsg) (2010) UICC: TNM Klassifikation maligner Tumoren, 7. Aufl. Wiley-VCH, Weinheim, ISBN 978-3-527-32759-1Google Scholar
  35. 35.
    Wittekind C, Meyer HJ, Bootz F (Hrsg) (2002) UICC: TNM Klassifikation maligner Tumoren, 6. Aufl. Springer, Berlin Heidelberg New York, ISBN 3-540-43664-2Google Scholar
  36. 36.
    Yothers GA, Allegra CJ, O’Connell MJ et al (2011) The efficacy of oxaliplatin (Ox) when added to 5-fluorouracil/leucovorin (FU/L) in stage II colon cancer. J Clin Oncol 29 (Suppl): Abstr 3507CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Medizinische Universitätsklinik, KnappschaftskrankenhausRuhr-Universität BochumBochumDeuschland

Personalised recommendations