EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer

J Van den Brande, P Schöffski, J H M Schellens, A D Roth, F Duffaud, K Weigang-Köhler, F Reinke, J Wanders, R F de Boer, J B Vermorken, P Fumoleau, J Van den Brande, P Schöffski, J H M Schellens, A D Roth, F Duffaud, K Weigang-Köhler, F Reinke, J Wanders, R F de Boer, J B Vermorken, P Fumoleau

Abstract

Cancer of the colon and rectum is one of the most frequent malignancies both in the US and Europe. Standard palliative therapy is based on 5-fluorouracil/folinic acid combinations, with or without oxaliplatin or irinotecan, given intravenously. Oral medication has the advantage of greater patient convenience and acceptance and potential cost savings. S-1 is a new oral fluorinated pyrimidine derivative. In a nonrandomized phase II study, patients with advanced/metastatic colorectal cancer were treated with S-1 at 40 mg m-2 b.i.d. for 28 consecutive days, repeated every 5 weeks, but by amendment the dose was reduced to 35 mg m-2 during the study because of a higher than expected number of severe adverse drug reactions. In total 47 patients with colorectal cancer were included. In the 37 evaluable patients there were nine partial responses (24%), 17 stable diseases (46%) and 11 patients had progressive disease (30%). Diarrhoea occurred frequently and was often severe: in the 40 and 35 mg m-2 group, respectively, 38 and 35% of the patients experienced grade 3-4 diarrhoea. The other toxicities were limited and manageable. S-1 is active in advanced colorectal cancer, but in order to establish a safer dose the drug should be subject to further investigations.

Figures

Figure 1
Figure 1
Composition of S-1.
Figure 2
Figure 2
Mechanism of S-1.

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