Capecitabine and oxaliplatin in the adjuvant treatment of stage III (Dukes' C) colon cancer

Colon cancer is a malignant neoplasm arising from the lining (mucosa) of the large intestine (colon). Colorectal cancer (including cancers of the rectum as well as cancers of the colon) is the third most common cancer in the UK. Almost 30,000 new cases were registered in England and Wales in 2002, representing over 12% of all new cancer cases. The incidence of colorectal cancer increases with age. In people between the ages of 45 and 49 years the incidence is about 20 per 100,000. Among those aged 75 and above, the rate is over 300 per 100,000 per year for men and over 200 per 100,000 per year for women.

In the UK, about 26% of patients diagnosed with colorectal cancer are classified as having stage III (or C1, C2 according to the modified Dukes' classification – patients whose tumour has spread to lymph nodes) disease at the time of presentation. These patients have an overall 5-year survival rate of between 25% and 60%. About two thirds of tumours develop in the colon and the remainder in the rectum. After a complete surgical resection (undertaken with curative intent), patients with stage III colon cancer have a 50% to 60% chance of developing recurrent disease.

NICE's cancer service guideline on improving outcomes in colorectal cancer recommends that systemic chemotherapy should be offered to all patients who, after surgery for Dukes' stage C colon or rectal cancer, are fit enough to tolerate it; that a multidisciplinary team should ensure that adjuvant chemotherapy is scheduled to begin within 6 weeks of surgery; and that standard treatment is a 6-month course of 5-fluorouracil and folinic acid (5-FU/FA), given intravenously. 5-FU/FA can be given in regimens involving bolus doses or continuous infusions.

In clinical trials of adjuvant chemotherapy for colon cancer, the outcome of treatment is usually reported in terms of disease-free survival. This is commonly defined as the time from randomisation to either the first relapse, a second primary colon cancer, death from any cause (with no evidence of relapse), or when the patient is disease free (censoring time). In some trials, relapse-free survival is used as a secondary outcome measure and is defined in the same way as disease-free survival, but excludes death unrelated to disease progression or treatment. Overall survival is also often reported as a secondary endpoint, but has disadvantages as an indicator of effectiveness. (In recurrent or advanced disease the activity of the adjuvant therapy may be masked by differences in subsequent therapy.) Pooled data suggest that 5-FU/FA regimens will increase disease-free survival at 5 years from 42% to 58%, and overall survival from 51% to 64%, when compared with surgery alone.