Colorectal cancer: the challenge

Colorectal cancer is a common cancer and a common cause of death. The incidence varies widely and is highest in industrialised Western countries. Surgery remains the mainstay of treatment of localised tumours and, in addition, may also play a role in some patients with local recurrence and/or isolated liver or lung metastases. Chemotherapy is required to improve the results of surgery and to treat patients with disseminated disease. For more than 30 years, 5-fluorouracil (5-FU) has been the only active agent in advanced colorectal cancer with an overall response rate of less than 15%. Biomodulation of 5-FU with leucovorin has led to a substantial increase in the response rate, but only a modest benefit in survival. Improvement in palliative effects has also been observed. In adjuvant treatment after curative surgery, 5-FU with levamisole or leucovorin has shown approximately a 10% absolute increase in survival, compared with controls. Despite this progress, there is evidence that an important proportion of colorectal cancer patients remains untreated. New treatments, such as the direct and specific thymidylate synthase inhibitors (e.g. 'Tomudex'--raltitrexed, previously known as ZD1694) in first-line therapy, or CPT-11 or oxaliplatin, along with increased referral and a more consistent treatment approach could improve the outcome of patients with advanced colorectal cancer.