Systemic treatment of advanced colorectal carcinoma

For advanced colorectal cancer (ACC), 5-fluorouracil (5-FU) based chemotherapy has been the standard for some decades. Attempts have been made to improve its results by biochemical modulation and schedule modulation of 5-FU which, in combination with leucovorin (LV), has been regarded as standard chemotherapy for almost two decades. The oral preparations capecitabine and uracil+ftorafur combined with LV may be regarded as a useful alternative to 5-FU/LV for the first line treatment of ACC. Irinotecan is widely accepted as the standard second line treatment Oxaliplatin + 5-FU/LV has been used in the neo-adjuvant setting in patients with initially irresectable liver metastasis. Both irinotecan and oxaliplatin + 5-FU/LV are also used in first line treatment However, it is still an open question whether the concomitant use of irinotecan or oxaliplatin with 5-FU/LV is really superior to the sequential use of these drugs. In patients with ACC anecdotal responses have been documented in small-scale studies with different types of cancer vaccines, either alone, or in combination as radioimmunotherapy. Favourable results were reported for the monoclonal antibody C225 (cetuximab) against the epidermal growth factor receptor in patients with ACC refractory to irinotecan. Vascular endothelial growth factor (VEGF) is an important angiogenic factor in colorectal cancer and is a marker for poor prognosis. Preliminary results of treatment with anti-VEGF antibody in combination with 5-FU/LV have shown encouraging results.