Current chemotherapeutic possibilities in the treatment of colorectal cancer

To date, the best treatment modality for colorectal cancer is a surgical excision of the primary tumour. Adjuvant therapy can be added to the surgical treatment and can consist of adjuvant chemo-, immuno- or radiotherapy. In the U.S.A., adjuvant chemotherapy with 5-fluorouracil (5FU) and levamisole is advocated as standard treatment for patients with localised poor risk (Dukes stage C) colon cancer. Not every clinician is convinced of the usefulness of adjuvant chemotherapy. Therefore, confirmatory clinical trials are still ongoing to compare no adjuvant treatment with SFU/levamisole adjuvant treatment. Treatment with SFU/leucovorin has been shown to be effective as adjuvant therapy. In rectal cancer, radiotherapy can be added to the primary surgical treatment. It is still unproven whether radiotherapy should be given pre-, peri, or postoperatively, and whether chemotherapy should be added to this multimodality regimen. If chemotherapy is applied as a radio-sensitiser, a continuous infusion is preferable to daily bolus injection. Much effort has been put into the improvement of the response rate of 10-15% 5FU, used as a single agent in the treatment of advanced colorectal cancer. Biochemical modulation of 5FU with leucovorin and interferon, different schedules of 5FU administration and hepatic arterial therapy have all been attempted. Higher response rates have been reported with these treatment modalities, unfortunately without improvement of survival, except for the intra-arterial approach. Recently, two new drugs have shown efficacy in the treatment of advanced colorectal cancer. A phase II trial with Tomudex (ZD1694), a new antifolate thymidylate synthase inhibitor, produced a response rate of 25% in patients with advanced colorectal cancer. A phase II trial with CPT-11, a topoisomerase I inhibitor, produced a response rate of 27% in patients with advanced disease and 25% response in patients with prior chemotherapy.