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Clin Colon Rectal Surg 2015; 28(04): 256-261
DOI: 10.1055/s-0035-1564430
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Chemotherapy for Stage II Colon Cancer

Anna Varghese
1   Division of Solid Tumor Oncology, Department of Medicine, Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, New York
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Publication History

Publication Date:
22 November 2015 (online)

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Abstract

The adjuvant treatment of patients with stage II colon cancer is an area of controversy in medical oncology. Adjuvant chemotherapy aims to eradicate micrometastatic disease present at the time of surgery, preventing the development of distant metastatic disease and thereby curing those patients of their cancer. National and international guidelines for the adjuvant treatment of stage II colon cancer recommend a range of treatment options from observation to chemotherapy with single-agent or combination regimens, depending on the presence or absence of high-risk features (poorly differentiated histology, presence of lymphovascular invasion, presence of perineural invasion, report of < 12 lymph nodes, bowel obstruction, localized perforation, or positive margins). In the one prospective study designed to address the role of adjuvant chemotherapy in stage II colon cancer, a small but statistically significant benefit in overall survival was seen for those patients who received adjuvant chemotherapy; however, multiple meta-analyses and retrospective subgroup analyses have called these findings into question. Though there may be a role for adjuvant chemotherapy in the treatment of patients with stage II colon cancer, its incremental benefit is small, at best, and comes with the risks of real and rarely fatal complications of chemotherapy.

Keywords

stage II colon cancer - adjuvant therapy - chemotherapy
 

  • References

  • 1 Moertel CG, Fleming TR, Macdonald JS , et al. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med 1995; 122 (5) 321-326
    CrossrefPubMedGoogle Scholar
  • 2 André T, Boni C, Mounedji-Boudiaf L , et al; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004; 350 (23) 2343-2351
    CrossrefPubMedGoogle Scholar
  • 3 Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65: 5-29
    CrossrefPubMedGoogle Scholar
  • 4 Gunderson LL, Jessup JM, Sargent DJ, Greene FL, Stewart AK. Revised TN categorization for colon cancer based on national survival outcomes data. J Clin Oncol 2010; 28 (2) 264-271
    CrossrefPubMedGoogle Scholar
  • 5 International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol 1999; 17 (5) 1356-1363
    CrossrefPubMedGoogle 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 (10) 1797-1806
    CrossrefPubMedGoogle Scholar
  • 7 NCCN Clinical Practice Guidelines in Oncology: Colon Cancer, National Comprehensive Cancer Network Colon Cancer (Version 3, 2015). http://www.nccn.org/professionals/physician_gls/pdf/colon.pdf . Accessed September 9, 2015
    PubMedGoogle Scholar
  • 8 Benson III 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 (16) 3408-3419
    CrossrefPubMedGoogle Scholar
  • 9 Labianca R, Nordlinger B, Beretta GD , et al; ESMO Guidelines Working Group. Early colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013; 24 (Suppl. 06) vi64-vi72
    PubMedGoogle Scholar
  • 10 Schrag D, Rifas-Shiman S, Saltz L, Bach PB, Begg CB. Adjuvant chemotherapy use for Medicare beneficiaries with stage II colon cancer. J Clin Oncol 2002; 20 (19) 3999-4005
    CrossrefPubMedGoogle Scholar
  • 11 Wolmark N, Fisher B, Rockette H , et al. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01. J Natl Cancer Inst 1988; 80 (1) 30-36
    CrossrefPubMedGoogle Scholar
  • 12 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 (9) 1466-1475
    PubMedGoogle Scholar
  • 13 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 (10) 1879-1887
    CrossrefPubMedGoogle Scholar
  • 14 Wolmark NRH, Rockette H, Mamounas EP , et al. The relative efficacy of 5-FU + leucovorin (FU-LV), 5-FU+levamisole (FU-LEV), and 5-FU + leucovorin + levamisole (FU-LV-LEV) in patients with Dukes' B and C carcinoma of the colon. Proc Am Soc Clin Oncol 1996; 15: 205
    PubMedGoogle Scholar
  • 15 Mamounas E, Wieand S, Wolmark N , et al. Comparative efficacy of adjuvant chemotherapy in patients with Dukes' B versus Dukes' C colon cancer: results from four National Surgical Adjuvant Breast and Bowel Project adjuvant studies (C-01, C-02, C-03, and C-04). J Clin Oncol 1999; 17 (5) 1349-1355
    PubMedGoogle Scholar
  • 16 Harrington DP. The tea leaves of small trials. J Clin Oncol 1999; 17 (5) 1336-1338
    PubMedGoogle Scholar
  • 17 Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ ; Quasar Collaborative Group. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet 2007; 370 (9604) 2020-2029
    CrossrefPubMedGoogle Scholar
  • 18 André T, Boni C, Navarro M , et al. 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 2009; 27 (19) 3109-3116
    CrossrefPubMedGoogle Scholar
  • 19 Tournigand C, André T, Bonnetain F , et al. Adjuvant therapy with fluorouracil and oxaliplatin in stage II and elderly patients (between ages 70 and 75 years) with colon cancer: subgroup analyses of the Multicenter International Study of Oxaliplatin, Fluorouracil, and Leucovorin in the Adjuvant Treatment of Colon Cancer trial. J Clin Oncol 2012; 30 (27) 3353-3360
    CrossrefPubMedGoogle Scholar
  • 20 Kuebler JP, Wieand HS, O'Connell MJ , et al. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol 2007; 25 (16) 2198-2204
    CrossrefPubMedGoogle Scholar
  • 21 Yothers G, O'Connell MJ, Allegra CJ , et al. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol 2011; 29 (28) 3768-3774
    CrossrefPubMedGoogle Scholar
  • 22 O'Connor ES, Greenblatt DY, LoConte NK , et al. Adjuvant chemotherapy for stage II colon cancer with poor prognostic features. J Clin Oncol 2011; 29 (25) 3381-3388
    CrossrefPubMedGoogle Scholar
  • 23 Hutchins G, Southward K, Handley K , et al. Value of mismatch repair, KRAS, and BRAF mutations in predicting recurrence and benefits from chemotherapy in colorectal cancer. J Clin Oncol 2011; 29 (10) 1261-1270
    CrossrefPubMedGoogle Scholar
  • 24 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 (3) 247-257
    CrossrefPubMedGoogle Scholar
  • 25 Sargent DJ, Marsoni S, Monges G , et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 2010; 28 (20) 3219-3226
    CrossrefPubMedGoogle Scholar
  • 26 Ng K, Schrag D. Microsatellite instability and adjuvant fluorouracil chemotherapy: a mismatch?. J Clin Oncol 2010; 28 (20) 3207-3210
    CrossrefPubMedGoogle Scholar
  • 27 Kim ST, Lee J, Park SH , et al. Clinical impact of microsatellite instability in colon cancer following adjuvant FOLFOX therapy. Cancer Chemother Pharmacol 2010; 66 (4) 659-667
    CrossrefPubMedGoogle Scholar
  • 28 Iwashyna TJ, Lamont EB. Effectiveness of adjuvant fluorouracil in clinical practice: a population-based cohort study of elderly patients with stage III colon cancer. J Clin Oncol 2002; 20 (19) 3992-3998
    CrossrefPubMedGoogle Scholar
  • 29 Sargent DJ, Goldberg RM, Jacobson SD , et al. A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 2001; 345 (15) 1091-1097
    CrossrefPubMedGoogle Scholar
  • 30 Gray RG, Quirke P, Handley K , et al. Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. J Clin Oncol 2011; 29 (35) 4611-4619
    CrossrefPubMedGoogle Scholar
  • 31 Kennedy RD, Bylesjo M, Kerr P , et al. Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue. J Clin Oncol 2011; 29 (35) 4620-4626
    CrossrefPubMedGoogle Scholar
  • 32 Salazar R, Roepman P, Capella G , et al. Gene expression signature to improve prognosis prediction of stage II and III colorectal cancer. J Clin Oncol 2011; 29 (1) 17-24
    CrossrefPubMedGoogle Scholar