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New possibilities in chemotherapy for colorectal cancer.

Colorectal cancer is the second leading cause of cancer death. Approximately 26,000 new cases are diagnosed yearly in France, resulting in more than 10,000 deaths, and 5-year survival remains low, at 40%. This poor prognosis is partly due to the fact that, in 30% of cases, colorectal cancer is metastatic or at a locally advanced stage when discovered. Moreover, visceral metastases complicate the development of the cancer after resection of the primary tumour in 40% to 50% of cases. The liver is the most frequently involved, followed by the abdominal lymph nodes, the peritoneum, the lungs, and far more rarely, the bones, adrenal glands or brain. Metastasis, whether synchronous or metachronous, most frequently occurs in the liver (around 40% of cases), thus exacerbating mortality [1,2]. The prognosis is poor for patients with visceral metastasis, and depends on such factors as the patient's general condition and the number and sites of metastatic disease. Nevertheless, several studies have shown that the prognosis for metastatic disease can be improved if treatment is aimed at 'curing' patients. Surgical resection of metastases, which is the first treatment option, is feasible, either immediately or after chemotherapy in only 10% of cases. The other cases are often candidates for systemic or locoregional chemotherapy treatment. The metastatic potential of colorectal carcinoma seems to correlate with the expression of certain oncoproteins involved in regulating apoptosis and the cell cycle. The presence of the p53 protein in the primary tumour is an indicator of liver and lymph node metastases. Also, overexpression of c-erb B2 in the primary tumour may be an indicator of potential metastasis, particularly in the liver [3]. Once the recently acquired knowledge in the molecular biology of colorectal cancer has been formally recognised as a factor for prognosis/prediction of natural history and/or tumoural response, this will lead to great changes in medical practice. During the last few decades, steady progress has been made in cancer treatment in terms of curability, survival duration and quality of life. This progress has varied according to the type of cancer. Major advances were made in the 1970s in the treatment of breast, testicular and childhood cancer; the end of the century will probably see advances in colorectal cancer treatment also. Improved diagnostic techniques, such as MRI (magnetic resonance imaging), PET (positron emission tomography), and CEA (Carcino-Embryonic Antigen) scanning, and the introduction of new chemotherapeutic agents, are no less important than improved knowledge about the disease. As a result of such innovations, a new multidisciplinary approach to colorectal cancer treatment has emerged, with new goals that replace those associated with standard treatment.