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

Van den Brande J, Schöffski P, Schellens JH, Roth AD, Duffaud F, Weigang-Köhler K, Reinke F, Wanders J, de Boer RF, Vermorken JB, Fumoleau P - Br. J. Cancer (2003)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium. jan.van.den.brande@uza.be

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.

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Composition of S-1.
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fig1: Composition of S-1.

Mentions: Therefore, new and better treatments and ways of delivering them are necessary. Oral medication has the advantage of greater patient convenience and acceptance and potential cost savings (DeMario and Ratain, 1998; Borner et al, 2002). 5-Fluorouracil itself is not suitable for oral administration because of the inability to achieve plasma concentrations of sufficient magnitude and the variability in oral bioavailability. Currently, there are several oral fluoropyrimidines in clinical practice or in advanced stages of development (Sharma et al, 2000). One of these agents is S-1. S-1 is a new oral fluorinated pyrimidine derivative, in which tegafur (FT) has been combined with two 5-FU modulating substances: 5-chloro-2,4-dihydroxypyridine (gimestat (Gimeracil®), CDHP), and potassium oxonate (otastat potassium (Oteracil®), Oxo), in a molar ratio of FT : CDHP : Oxo=1 : 0.4 : 1 (Figure 1Figure 1


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

Van den Brande J, Schöffski P, Schellens JH, Roth AD, Duffaud F, Weigang-Köhler K, Reinke F, Wanders J, de Boer RF, Vermorken JB, Fumoleau P - Br. J. Cancer (2003)

Composition of S-1.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376342&req=5

fig1: Composition of S-1.
Mentions: Therefore, new and better treatments and ways of delivering them are necessary. Oral medication has the advantage of greater patient convenience and acceptance and potential cost savings (DeMario and Ratain, 1998; Borner et al, 2002). 5-Fluorouracil itself is not suitable for oral administration because of the inability to achieve plasma concentrations of sufficient magnitude and the variability in oral bioavailability. Currently, there are several oral fluoropyrimidines in clinical practice or in advanced stages of development (Sharma et al, 2000). One of these agents is S-1. S-1 is a new oral fluorinated pyrimidine derivative, in which tegafur (FT) has been combined with two 5-FU modulating substances: 5-chloro-2,4-dihydroxypyridine (gimestat (Gimeracil®), CDHP), and potassium oxonate (otastat potassium (Oteracil®), Oxo), in a molar ratio of FT : CDHP : Oxo=1 : 0.4 : 1 (Figure 1Figure 1

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium. jan.van.den.brande@uza.be

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.

Show MeSH
Related in: MedlinePlus