New developments in systemic chemotherapy in advanced colorectal cancer

The majority of patients with newly diagnosed colorectal cancer who present with concurrent metastases are considered to be incurable from the disease. For their treatment, these patients depend on systemic anticancer therapy and supportive care.

This article reviews recent developments in systemic treatment of disseminated colorectal cancer.

Until recently, the fluoropyrimidines were the only cytotoxic drugs available, but during recent years three other classes of active conventional cytotoxic drugs and a new class of target-directed drugs have become available. New cytotoxic drug therapies include raltitrexed, irinotecan and oxaliplatin. Patients receiving irinotecan experience a better quality of life than those treated with best supportive care alone. Irinotecan or oxaliplatin in combination with 5-fluoro-uracil (5-FU) and leucovorin are currently the most active treatment regimens. Oral prodrugs of 5-FU, such as capecitabine and uracil, have been developed in order to mimic the protracted infusion schedule of 5-FU, and these drugs may change the daily practice of palliative chemotherapy for colorectal cancer in the coming years. Therapeutic agents that target specific molecular processes that promote proliferation, vascularization and metastasis, and inhibit apoptosis, are being designed and may offer a rational approach to anticancer therapy. Examples of this novel approach are monoclonal antibodies and small molecules adhering to the epithelial growth factor receptor and vascular endothelial growth factor receptor in order to inhibit growth stimulation and angiogenesis.

The current debate is no longer whether to use palliative chemotherapy in metastatic colorectal, but which patient will benefit from which combination and in what sequence.