Novel platinum compounds have been sought with the goal of identifying molecules active in cisplatin-resistant cancers such as colorectal cancer. Some 30 years ago it was shown that varying the structure of the coordination complex could enhance the activity of platinum compounds against preclinical models. The diaminocyclohexane ligand, now embodied in the structure of oxaliplatin, was the most promising of a series of such analogues. Oxaliplatin has recently been approved in the United States for the treatment of refractory colorectal cancer. Studies in the initial treatment of advanced disease indicate that its activity when used in combination with 5-fluorouracil (5-FU) is at least as good as standard therapy for this stage of the disease. Novel combinations have been reported in phase II studies, and adjuvant trials have been completed in the United States and Europe. It is reasonable to conclude that there are now two accepted regimens for the treatment of colorectal cancer, irinotecan/5-FU and oxaliplatin/5-FU. Early studies using both regimens sequentially are of interest, and phase I trials of three-drug combinations have been presented. Current efforts are directed toward individualizing therapy through predictive analyses of the targets and metabolic pathways of all three agents in pharmacogenetic and pharmacogenomic studies.
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