What is the recommended adjuvant treatment for stage III colon cancer patients with Microsatellite Instability (MSI)-high status?

From the Guidelines

For stage III colon cancer patients with Microsatellite Instability (MSI)-high status, the recommended adjuvant treatment is typically single-agent fluoropyrimidine therapy, specifically capecitabine (1250 mg/m² twice daily for 14 days, followed by 7 days off) or 5-fluorouracil (5-FU) with leucovorin for a total duration of 6 months. This recommendation is based on the understanding that MSI-high tumors have deficient mismatch repair mechanisms, which creates a hypermutated phenotype that responds differently to chemotherapy agents 1.

Key Considerations

• The American Society of Clinical Oncology (ASCO) guidelines suggest that for patients with completely resected stage III colon cancer, adjuvant chemotherapy with oxaliplatin and a fluoropyrimidine may be offered for a duration of 6 months for high-risk patients (T4 and/or N2), but for low-risk patients, either 6 months or a shorter duration of 3 months may be considered 1.
• However, for MSI-high tumors, the benefit from oxaliplatin-based combination chemotherapy is less compared to fluoropyrimidine monotherapy, making single-agent fluoropyrimidine therapy a preferred option.
• Patients should be monitored for side effects including diarrhea, hand-foot syndrome, mucositis, and myelosuppression.
• Regular follow-up with carcinoembryonic antigen (CEA) testing, imaging, and colonoscopy is essential after completion of adjuvant therapy to monitor for recurrence.

Treatment Approach

• The choice between capecitabine and 5-FU with leucovorin should be based on patient factors, including tolerance to potential side effects and convenience of administration.
• A shared decision-making approach is recommended, taking into account patient characteristics, values, and preferences, as well as the potential benefits and risks associated with treatment duration 1.

From the FDA Drug Label

Oxaliplatin Injection, in combination with infusional fluorouracil and leucovorin, is indicated for: adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor.

The recommended adjuvant treatment for stage III colon cancer patients is oxaliplatin in combination with infusional fluorouracil and leucovorin.

• Key components of the treatment:
  • Oxaliplatin 85 mg/m2 as an intravenous infusion over 120 minutes
  • Leucovorin 200 mg/m2 as an intravenous infusion over 120 minutes
  • Fluorouracil 400 mg/m2 as intravenous bolus over 2-4 minutes, followed by fluorouracil 600 mg/m2 as a 22-hour continuous infusion
• Treatment duration: up to 12 cycles or unacceptable toxicity 2

From the Research

Adjuvant Treatment for Stage III Colon Cancer with MSI-High Status

• The recommended adjuvant treatment for stage III colon cancer patients with Microsatellite Instability (MSI)-high status is a combination of fluoropyrimidine and oxaliplatin chemotherapy 3.
• The "French National Thesaurus of Digestive Oncology" suggests adjuvant chemotherapy combining fluoropyrimidine and oxaliplatin for stage III MSI colon cancer 3.
• Oxaliplatin-based chemotherapy (FOLFOX or XELOX) for 6 months is the current standard for adjuvant therapy of stage III colon cancer patients with good performance status 4.
• However, a reduced duration of adjuvant therapy (3 months) may be considered to reduce overall toxicity while maintaining overall clinical efficacy, depending on patient-based risk factors 4, 5, 6.

Duration of Adjuvant Treatment

• The International Duration Evaluation of Adjuvant (IDEA) study aimed to evaluate the noninferiority of 3-month compared with 6-month adjuvant oxaliplatin-based treatment in stage III colon cancer 4.
• The results of the IDEA study and other trials suggest that the choice of regimen and duration should depend on patient characteristics and be balanced against the extra toxicity of longer therapy 5, 6.

Efficacy of Adjuvant Chemotherapy in MSI-High Stage III Colon Cancer

• A study found that FOLFOX chemotherapy can be considered to treat stage III colon cancer patients with MSI-H after surgery, with no significant difference in 5-year disease-free and overall survival compared to MSI-L/MSS colon cancer 7.
• Another study suggests that the MSI status would also be a biomarker able to predict the lack of efficacy of adjuvant 5-fluorouracil (5FU) chemotherapy, and that MSI tumors would have a survival benefit with the addition of oxaliplatin to adjuvant 5FU chemotherapy 3.