For a 60-year-old man with high-risk stage II (pT4a N0 M0) mucinous adenocarcinoma of the cecum/ileocecal junction, is CAPOX (capecitabine + oxaliplatin) or FOLFOX (oxaliplatin + infusional 5-fluorouracil + leucovorin) the preferred adjuvant chemotherapy regimen?

CAPOX is the Preferred Regimen for This Patient

For a 60-year-old man with high-risk stage II (pT4a N0 M0) mucinous adenocarcinoma of the cecum/ileocecal junction, CAPOX is the preferred adjuvant chemotherapy regimen over FOLFOX. 1, 2

Guideline-Based Recommendation

The 2025 Chinese Society of Clinical Oncology guidelines explicitly prefer CAPOX (XELOX) over mFOLFOX6 for high-risk stage II colon cancer, giving it a Grade 1A recommendation. 1, 2 This patient meets multiple high-risk criteria that mandate oxaliplatin-based combination chemotherapy:

• T4a tumor (transmural invasion through the serosa) 1, 2
• Mucinous histology (associated with poor differentiation) 2
• Ileocecal junction location 2

Both NCCN and CSCO guidelines classify CAPOX and FOLFOX as equivalent Category 1 options for efficacy in high-risk stage II disease, but CAPOX offers practical advantages that make it the preferred choice. 1, 3, 2

Treatment Duration: Full 6 Months Required

This patient requires a full 6-month course of adjuvant chemotherapy regardless of regimen choice. 1, 2 The IDEA trial demonstrated that 3-month CAPOX is inferior to 6 months in high-risk populations (T4 disease), with a hazard ratio of 1.41 (95% CI 1.08-1.84). 2, 4 For high-risk stage II patients with T4 tumors, shortening treatment duration compromises efficacy. 4

Standard CAPOX Dosing (6 months)

• Oxaliplatin 130 mg/m² IV on day 1
• Capecitabine 1,000 mg/m² orally twice daily, days 1-14
• Repeat every 3 weeks for 8 cycles (total 6 months) 1, 2

Note: North American patients may require the lower starting dose of 1,000 mg/m² rather than 1,250 mg/m² due to increased toxicity compared to European cohorts. 3, 2

Why CAPOX Over FOLFOX for This Patient

Practical Advantages

• No central venous catheter required – eliminates catheter-related complications and infections 2
• No continuous infusion pump needed – improves patient convenience and quality of life 2
• Equivalent efficacy – both regimens achieve similar response rates, time to progression, and overall survival in high-risk stage II disease 3, 5

Toxicity Profile Considerations

While CAPOX shows higher rates of hand-foot syndrome (20%) and diarrhea (32%) compared to FOLFOX, it demonstrates significantly less myelosuppression. 1, 2 Grade 3-4 neutropenia occurs in only 7% of CAPOX patients versus higher rates with FOLFOX. 1 FOLFOX causes more mucositis and neutropenia. 2

Both regimens produce similar rates of oxaliplatin-induced peripheral neuropathy (approximately 85% any grade), which is the dose-limiting toxicity for both. 5

When FOLFOX Should Be Selected Instead

FOLFOX remains the appropriate choice if the patient has:

• Severe renal impairment (creatinine clearance < 30 mL/min) – capecitabine is contraindicated 3, 2
• Inability to tolerate oral medications – due to persistent nausea, dysphagia, or malabsorption 3, 2
• Concerns about medication adherence – twice-daily oral dosing may be problematic 3, 2

Critical Timing and Monitoring

Initiate chemotherapy within 8 weeks of surgery. 2 Delays beyond 8 weeks significantly increase mortality risk (HR 1.20; P = 0.001). 2 Treatment should begin around 3 weeks postoperatively once the patient has recovered adequately. 1

Required Monitoring

• Complete blood counts, liver function, and renal function before each cycle 3
• Assess for peripheral neuropathy before each oxaliplatin dose 3
• CEA every 3 months during treatment and for 2 years after, then every 6 months for years 3-5 3

Neuropathy Management

If grade ≥2 neurotoxicity develops after 3-4 months, discontinue oxaliplatin and continue fluoropyrimidine monotherapy to prevent permanent neuropathy. 3 Do not continue oxaliplatin beyond 3-4 months if significant neurotoxicity emerges. 3

Prohibited Additions

Do not add bevacizumab, cetuximab, panitumumab, or irinotecan to either CAPOX or FOLFOX in the adjuvant setting outside of clinical trials. 1, 3, 2 These agents have not demonstrated benefit and add unnecessary toxicity and cost.

MMR Status Consideration

Although not specified in this case, if this patient's tumor demonstrates deficient mismatch repair (dMMR) or MSI-H status, observation alone would be preferred over any chemotherapy, as dMMR stage II patients have excellent prognosis and do not benefit from fluoropyrimidine-based adjuvant therapy. 1 However, given the T4a status and mucinous histology, this tumor is more likely proficient MMR (pMMR), which supports the recommendation for oxaliplatin-based combination therapy.