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Adjuvant therapy for stage II colorectal cancer: Who and with what?

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The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-riskrd stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and metaanalyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-riskrd stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

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References and Recommended Reading

  1. Jemal A, Tiwari RC, Murray T, et al.: Cancer statistics, 2004. CA Cancer J Clin 2004, 54:8–29.

    Article  PubMed  Google Scholar 

  2. Greene F, Page DL, Fleming ID, et al. The AJCC Staging Handbook, edn 6. New York: Springer; 2002.

    Google Scholar 

  3. Compton CC: Pathology report in colon cancer: What is prognostically important? Dig Dis 1999, 17:67–79.

    Article  PubMed  CAS  Google Scholar 

  4. Compton CC: Updated protocol for the examination of specimens from patients with carcinomas of the colon and rectum, excluding carcinoid tumors, lymphomas, sarcomas, and tumors of the vermiform appendix: a basis for checklists. Cancer Committee. Arch Pathol Lab Med 2000, 124:1016–1025.

    PubMed  CAS  Google Scholar 

  5. Nauta R, Stablein DM, Holyoke ED: Survival of patients with stage B2 colon carcinoma. The Gastrointestinal Tumor Study Group experience. Arch Surg 1989, 124:180–182.

    PubMed  CAS  Google Scholar 

  6. Gill S, Loprinzi CL, Sargent DJ, et al.: Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: Who benefits and by how much? J Clin Oncol 2004, 22:1797–1806. This meta-analysis of seven large randomized trials demonstrated no significant survival benefit for adjuvant chemotherapy for stage II patients.

    Article  PubMed  CAS  Google Scholar 

  7. Benson AB, Schrag D, Somerfield MR, et al.: American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 2004, 22:3408–3419.

    Article  PubMed  Google Scholar 

  8. Moertel CG, Fleming TR, Macdonald JS, et al.: Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med 1990, 322:352–358.

    Article  PubMed  CAS  Google Scholar 

  9. Moertel CG, Fleming TR, Macdonald JS, et al.: Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes’ B2 colon cancer. J Clin Oncol 1995, 13:2936–2943.

    PubMed  CAS  Google Scholar 

  10. Le Voyer TE, Sigurdson ER, Hanlon AL, et al.: Colon cancer survival is associated with increasing number of lymph nodes analyzed: a secondary survey of intergroup trial INT-0089. J Clin Oncol 2003, 21:2912–2919.

    Article  PubMed  Google Scholar 

  11. Gray RG, Barnwell J, Hills R: QUASAR: a randomized study of adjuvant chemotherapy vs observation including 3238 colorectal cancer patients. Proceedings of the American Society of Clinical Oncology 2004. Alexandria, VA: American Society of Clinical Oncology; 2004. Adjuvant therapy provides a non-statistically significant 1% to 5% survival benefit in stage II patients that may reach statistical significance with time, as recurrence risk with adjuvant chemotherapy is clearly reduced.

    Google Scholar 

  12. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. J Clin Oncol 1999, 17:1356–1363. No advantage is found for adjuvant chemotherapy, considering the 75% to 80% 5-year survival rate for stage II patients after surgery alone and a 0.5% to 1.0% mortality associated with adjuvant 5-FU/LV.

  13. Andre T, Boni C, Mounedji-Boudiaf L, et al.: Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004, 350:2343–2351. A non-statistically significant 2.7% improvement in OS for stage II patients must be tempered with the significant toxicities of therapy. On the basis of this study, the FDA approved the use of adjuvant 5-FU, LV, and oxaliplatin (FOLFOX-4) for patients with stage III colon cancer only.

    Article  PubMed  CAS  Google Scholar 

  14. Hickish T, Boni C, Navarro M: FOLFOX-4 as adjuvant treatment for stage II colon cancer: subpopulation data from the MOSAIC trial. Proceedings of the American Society of Clinical Oncology 2004. Alexandria, VA: American Society of Clinical Oncology; 2004.

    Google Scholar 

  15. Schrag D, Rifas-Shiman S, Saltz L, et al.: Adjuvant chemotherapy use for Medicare beneficiaries with stage II colon cancer. J Clin Oncol 2002, 20:3999–4005.

    Article  PubMed  CAS  Google Scholar 

  16. Wolmark N, Rockette H, Wickerham DL, et al.: Adjuvant therapy of Dukes’ A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02. J Clin Oncol 1990, 8:1466–1475.

    PubMed  CAS  Google Scholar 

  17. Wolmark N, Rockette H, Fisher B, et al.: The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol 1993, 11:1879–1887.

    PubMed  CAS  Google Scholar 

  18. Wolmark N, Rockette H, Mamounas E, et al.: Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes’ B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol 1999, 17:3553–3559.

    PubMed  CAS  Google Scholar 

  19. Figueredo A, Charette ML, Maroun J, et al.: Adjuvant therapy for stage II colon cancer: a systematic review from the Cancer Care Ontario Program in evidencebased care’s gastrointestinal cancer disease site group. J Clin Oncol 2004, 22:3395–3407.

    Article  PubMed  Google Scholar 

  20. Horn A, Dahl O, Morild I: Venous and neural invasion as predictors of recurrence in rectal adenocarcinoma. Dis Colon Rectum 1991, 34:798–804.

    Article  PubMed  CAS  Google Scholar 

  21. Knudsen JB, Nilsson T, Sprechler M, et al.: Venous and nerve invasion as prognostic factors in postoperative survival of patients with resectable cancer of the rectum. Dis Colon Rectum 1983, 26:613–617.

    Article  PubMed  CAS  Google Scholar 

  22. Jen J, Kim H, Piantadosi S, et al.: Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med 1994, 331:213–221.

    Article  PubMed  CAS  Google Scholar 

  23. Ribic CM, Sargent DJ, Moore MJ, et al.: Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 2003, 349:247–257.

    Article  PubMed  CAS  Google Scholar 

  24. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. Meta-Analysis Group In Cancer. J Clin Oncol 1998, 16:3537–3541.

  25. Efficacy of intravenous continuous infusion of fluorouracil compared with bolus administration in advanced colorectal cancer. Meta-analysis Group In Cancer. J Clin Oncol 1998, 16:301–308.

  26. Twelves C, Wong A, Nowacki MP, et al.: Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005, 352:2696–2704.

    Article  PubMed  CAS  Google Scholar 

  27. Saltz LB, Cox JV, Blanke C, et al.: Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med 2000, 343:905–914.

    Article  PubMed  CAS  Google Scholar 

  28. Hurwitz H, Fehrenbacher L, Novotny W, et al.: Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004, 350:2335–2342.

    Article  PubMed  CAS  Google Scholar 

  29. Saltz LB, Rubin M, Hochster H, et al.: Cetuximab (IMCC225) plus irinotecan (CPT-11) is active in CPT-11-refractory colorectal cancer (CRC) that express epidermal growth factor receptor(EGFR) [abstract]. Proceedings of the American Society of Clinical Oncology 2001. Alexandria, VA: American Society of Clinical Oncology; 2001. Abstract 7.

    Google Scholar 

  30. Saltz LB, Meropol NJ, Loehrer PJ, et al.: Phase II trial of cetuximab in patients with refractory colorectal cancer that expresses the epidermal growth factor receptor. J Clin Oncol 2004, 22:1201–1208.

    Article  PubMed  CAS  Google Scholar 

  31. Cunningham D, Humblet Y, Siena S, et al.: Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004, 351:337–345.

    Article  PubMed  CAS  Google Scholar 

  32. Badarinath S, Mitchell EP, Jennis A: Cetuximab plus FOLFOX for colorectal (EXPLORE): preliminary safety analysis of a randomized phase III trial. Proceedings of the American Society of Clinical Oncology 2004. Alexandria, VA: American Society of Clinical Oncology; 2004.

    Google Scholar 

  33. Chung KY, Shia J, Kemeny NE, et al.: Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 2005, 23:1803–1810.

    Article  PubMed  CAS  Google Scholar 

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Chung, KY.Y., Kelsen, D. Adjuvant therapy for stage II colorectal cancer: Who and with what?. Curr Treat Options Gastro 9, 272–280 (2006). https://doi.org/10.1007/s11938-006-0046-z

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