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To evaluate the reliability and validity of serum carcinoembryonic antigen (CEA), tissue polypeptide-specific antigen (TPS), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in monitoring palliative chemotherapy in advanced colorectal cancer (ACRC).Serum was prospectively collected from 87 patients with ACRC treated with first-line 5-fluorouracil and leucovorin before and 2, 4 and 10 weeks after induction.Eight patients had normal baseline TPS levels, and these patients had a favourable outcome with prolonged survival and a higher rate of objective responses than patients with elevated TPS levels. At 10 weeks, all responders had a decreasing TPS value. The sensitivity for a decrease of >25% using TPS was 83% and 86% for objective and subjective responses, respectively, and the specificity was 65% and 72%, respectively. CEA had, in the same setting, a sensitivity of 45% and 46%, respectively, and the specificity was 88%. VEGF was elevated in 54% of the patients and bFGF in 15% of the patients. The VEGF values decreased during therapy in 94% of the patients, but the changes in serial VEGF values did not correlate with survival or response. Tumour markers used together did not enhance the predictive values of TPS alone.Repeated measurements of CEA, VEGF and bFGF in serum are of limited value in monitoring chemotherapy in ACRC. TPS seems to be of greater interest, but does not predict exactly which patients are going to have a positive outcome of palliative chemotherapy.