Colon cancer, RAS wild-type

Section editor
	Travis Zack, MD, PhD University of California San Francisco San Francisco, CA, USA LinkedIn

Note: the page has adjuvant regimens specific to RAS wild-type colon cancer. Also note that most of the regimens were evaluated on patients tested for KRAS mutations only, and that the definition of wild-type has evolved over time. See individual regimen biomarker eligibility criteria for more details.

• See the main colon cancer page for general regimens.

2 regimens on this page 2 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any article published 5+ years ago to be for historical purposes, only.

ESMO

• 2013: Early Colon Cancer: ESMO Clinical Practice Guidelines PubMed
• 2013: Familial risk-colorectal cancer: ESMO Clinical Practice Guidelines. PubMed

Japanese Society for Cancer of the Colon and Rectum

• 2016: Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer PubMed

NCCN

• NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Colon Cancer.

Adjuvant therapy

mFOLFOX6

mFOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Alberts et al. 2012 (N0147)	2004-2009	Phase 3 (C)	mFOLFOX6 & Cetuximab	Might have superior DFS DFS36: 74.6% vs 71.5% (HR 0.83, 95% CI 0.67-1.02)

Preceding treatment

• Surgery, within 10 weeks

Chemotherapy

• Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 2400 mg/m² IV continuous infusion over 46 to 48 hours, given second (total dose per cycle: 2800 mg/m²)
• Leucovorin (Folinic acid) 400 mg/m² IV over 2 hours once on day 1, given first, with oxaliplatin
• Oxaliplatin (Eloxatin) 85 mg/m² IV over 2 hours once on day 1, given first, with folinic acid

14-day cycle for 12 cycles

References

1. N0147: Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, Smyrk TC, Sinicrope FA, Chan E, Gill S, Kahlenberg MS, Shields AF, Quesenberry JT, Webb TA, Farr GH Jr, Pockaj BA, Grothey A, Goldberg RM. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00079274

mFOLFOX6 & Cetuximab

mFOLFOX6 & Cetuximab: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Cetuximab

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Alberts et al. 2012 (N0147)	2004-2009	Phase 3 (E-esc)	mFOLFOX6	Might have inferior DFS (primary endpoint) DFS36: 71.5% vs 74.6% (HR 1.21, 95% CI 0.98-1.49)

Some guidelines do not recommend using cetuximab as adjuvant therapy outside of a clinical trial.

Preceding treatment

• Surgery, within 10 weeks

Chemotherapy

• Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 2400 mg/m² IV continuous infusion over 46 to 48 hours (total dose per cycle: 2800 mg/m²)
• Leucovorin (Folinic acid) 400 mg/m² IV over 2 hours once on day 1
• Oxaliplatin (Eloxatin) 85 mg/m² IV over 2 hours once on day 1

Targeted therapy

• Cetuximab (Erbitux) as follows:
  • Cycle 1: 400 mg/m² IV over 2 hours once on day 1, then 250 mg/m² IV over 60 minutes once on day 8
  • Cycles 2 to 12: 250 mg/m² IV over 2 hours once per day on days 1 & 8

14-day cycle for 12 cycles

References

1. N0147: Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, Smyrk TC, Sinicrope FA, Chan E, Gill S, Kahlenberg MS, Shields AF, Quesenberry JT, Webb TA, Farr GH Jr, Pockaj BA, Grothey A, Goldberg RM. 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. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00079274