Adjuvant therapy for stage III colon cancer

From Cancer Guidelines Wiki

Background

Patients with stage III (T1 to T4, N1-2) or Dukes C colon cancer have 5-year disease-free survival of around 49%, improving to 64% with the addition of adjuvant chemotherapy.[1] The benefit of adjuvant treatment has been demonstrated,[2] meaning 6 months of adjuvant chemotherapy should be offered to patients with stage III colon cancer, unless medically unfit, with the aim of improving relapse free and overall survival.[3]Back to top

Overview of evidence (non-systematic literature review)

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

Addition of oxaliplatin to 5FU-based regimens

The efficacy of oxaliplatin plus 5-fluorouracil5-fluorouracil is a systemic chemotherapy using fluorouracil. (5FU) as adjuvant therapy for stage III disease was demonstrated in two pivotal randomised controlled trials (RCTs): the MOSAIC study[4] and the NSABP C07 study.[5] Both studies included stage II and III patients.

In the MOSAIC trial,[4] 2246 patients were randomised to receive a combined bolus/infusional leucovorin (LV) plus 5FU regimen (LV5FU2) alone, or with oxaliplatin (FOLFOX4), for 6 months. On final analysis, the 10-year overall survival rates for patients with stage III disease were 59.0% and 67.1%, respectively (hazard ratio [HR] 0.80; p = .016).[4]

The NSABP C07 trial[5] randomised 2492 patients to either 5FU 500 mg/m2, plus LV 500 mg/m2 both IV weekly for 6 weeks during each 8-week cycle (Roswell Park regimen) for three cycles, or the same 5FU-LV regimen with oxaliplatin 85 mg/m2 IV administered on weeks one, three and five of each 8-week cycle for three cycles. This study confirmed the additional disease-free survival benefit provided by oxaliplatin, as observed in the MOSAIC trial.[5] No benefit for overall survival was found.

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Addition of oxaliplatin to capecitabine (XELOX)

A subsequent RCTA study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control., the NO1968 study, compared capecitabine plus oxaliplatin (XELOX; oxaliplatin 130 mg/m2 on day one plus capecitabine 1000 mg/m2 b.i.d on days one to 14, every 3 weeks for 24 weeks) with a control arm of bolus 5FU-LV (Mayo Clinic for 24 weeks or Roswell Park for 32 weeks) in patients with stage III colon cancer.[6] The 3-year disease-free survival rate was 70.9% with XELOX and 66.5% with 5FU-LV (HR 0.80, p < 0.005).[6] XELOX is thus considered an additional adjuvant treatment option for patients with stage III colon cancer.


Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Oxaliplatin in combination with a fluoropyrimidine is standard therapy for young patients (< 70 years) with stage III colon cancer.

Practice pointA recommendation on a subject that is outside the scope of the search strategy for the systematic review, based on expert opinion and formulated by a consensus process.Question mark transparent.png

Capecitabine plus oxaliplatin (XELOX) can be considered as an alternative to FOLFOXSystemic chemotherapy using a combination of the drugs Leucovorin (folinic acid), Fluorouracil, and Oxaliplatin. for adjuvant treatment for patients with stage III colon cancer.

Next section: adjuvant therapy elderly stage III CRC
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References

  1. Böckelman C, Engelmann BE, Kaprio T, Hansen TF, Glimelius B. Risk of recurrence in patients with colon cancer stage II and III: a systematic review and meta-analysis of recent literature. Acta Oncol 2015 Jan;54(1):5-16 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25430983.
  2. Lombardi L, Gebbia V, Silvestris N, Testa A, Colucci G, Maiello E. Adjuvant therapy in colon cancer. Oncology 2009;77 Suppl 1:50-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20130432.
  3. National Comprehensive Cancer Network. NCCN Guidelines: Colon Cancer. National Comprehensive Cancer Network; 2016.
  4. 4.04.14.2 André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, et al. Adjuvant Fluorouracil, Leucovorin, and Oxaliplatin in Stage II to III Colon Cancer: Updated 10-Year Survival and Outcomes According to BRAF Mutation and Mismatch Repair Status of the MOSAIC Study. J Clin Oncol 2015 Dec 10;33(35):4176-87 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26527776.
  5. 5.05.15.2 Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, 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 Oct 1;29(28):3768-74 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21859995.
  6. 6.06.1 Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, et al. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 2011 Apr 10;29(11):1465-71 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21383294.
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