Colorectal cancer

Irinotecan and targeted (biological) agents in adjuvant therapy for stage II and stage III colon cancer

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Clinical practice guidelines for the prevention, early detection and management of colorectal cancer > Irinotecan and targeted (biological) agents in adjuvant therapy for stage II and stage III colon cancer

Background[edit source]

Overview of evidence (non-systematic literature review)[edit source]

No systematic reviews were undertaken for this topic. Practice points were based on selected published evidence. See Guidelines development process.

Irinotecan[edit source]

Three prospective randomised trials[1][2][3] failed to demonstrate a benefit from the addition of irinotecan to fluorouracil in patients with stage II or III colon cancer.

Targeted (biological) therapies[edit source]

The addition of biologic agents to conventional adjuvant therapy has not led to any patient benefit.

The addition of the anti-angiogenic targeted therapy bevacizumab to FOLFOX failed to benefit patients with stage II or III colon cancer in two large phase III trials[4][5] and a similar lack of benefit was seen with the addition of bevacizumab to capecitabine[6]. These findings prompted the early closure of the Eastern Cooperative Oncology Group (ECOG) E5202 trial of adjuvant FOLFOX with and without bevacizumab in high-risk Stage II patients. No data from this study have been presented or published.

The pivotal phase III trial of adjuvant chemotherapy incorporating the anti-EGFR targeted therapy cetuximab (NCCTG-NO147) was also negative.[7] The trial had been modified to include patients with wild-type KRAS only when data regarding the predictive value of KRAS testing for response to the anti-EGFR antibodies became available, however in the wild-type KRAS subgroup the addition of cetuximab in the adjuvant setting did not confer benefit and analysis of the mutant KRAS population (enrolled prior to the amendment) showed a detrimental effect for the addition of cetuximab. The Pan-European PETACC-8 study with a similar randomisation to FOLFOX with or without cetuximab[8] has completed recruitment and again saw no impact on progression free survival in patients with wild-type KRAS.

Practice pointQuestion mark transparent.png

Neither Irinotecan nor a biological agent (either bevacizumab or cetuximab) should be used as adjuvant therapy for patients with stage II or III colon cancer.

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References[edit source]

  1. Saltz LB, Niedzwiecki D, Hollis D, Goldberg RM, Hantel A, Thomas JP, et al. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol 2007 Aug 10;25(23):3456-61 Available from:
  2. Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B, et al. 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 2009 Jul 1;27(19):3117-25 Available from:
  3. Ychou M, Raoul JL, Douillard JY, Gourgou-Bourgade S, Bugat R, Mineur L, et al. A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802). Ann Oncol 2009 Apr;20(4):674-80 Available from:
  4. Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Lopa SH, et al. Bevacizumab in stage II-III colon cancer: 5-year update of the National Surgical Adjuvant Breast and Bowel Project C-08 trial. J Clin Oncol 2013 Jan 20;31(3):359-64 Available from:
  5. de Gramont A, Van Cutsem E, Schmoll HJ, Tabernero J, Clarke S, Moore MJ, et al. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol 2012 Dec;13(12):1225-33 Available from:
  6. Kerr RS, Love S, Segelov E, Johnstone E, Falcon B, Hewett P, et al. Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial. Lancet Oncol 2016 Nov;17(11):1543-1557 Available from:
  7. Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, et al. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA 2012 Apr 4;307(13):1383-93 Available from:
  8. Taieb J, Tabernero J, Mini E, Subtil F, Folprecht G, Van Laethem JL, et al. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial. Lancet Oncol 2014 Jul;15(8):862-73 Available from:

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