Chemotherapy with leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) is most appropriate for this patient with stage III colon cancer. Stage III colon cancer is potentially curable, and the likelihood of cure is modestly but statistically significantly increased by the use of adjuvant chemotherapy. Administration of leucovorin plus 5-fluorouracil (5-FU) was established as an appropriate standard adjuvant treatment for stage III colon cancer in the 1990s. However, in 2004, a large randomized trial comparing adjuvant leucovorin and 5-FU with FOLFOX adjuvant chemotherapy showed that the FOLFOX regimen led to improved disease-free and overall survival. Capecitabine is an oral prodrug that is converted to 5-FU in the body. The combination of capecitabine plus intravenous oxaliplatin (CAPOX) is also an acceptable regimen for adjuvant treatment of patients with stage III colon cancer.

Because local recurrence of colon cancer rarely develops and because it can be difficult to isolate the small bowel from the radiation field, radiation therapy, either alone or in combination with chemotherapy, does not have a role in the routine management of patients with stage III colon cancer. In addition, radiation to the small bowel may cause substantial toxicity. However, because local recurrence is a greater problem in patients with rectal cancer and because it is far easier to isolate the small bowel from the radiation field when treating rectal cancer, the combination of radiation therapy and chemotherapy, preferably preoperatively, is routinely used for treating patients with stage II and III rectal cancer.

Stage III colon cancer is potentially curable with surgery and adjuvant chemotherapy. For patients with good performance status, adjuvant chemotherapy with its associated survival advantage is preferred to observation alone.