title: EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer.
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.
authors.affiliation: Department of Medical Oncology, University Hospital Antwerp, Wilrijkstraat, Edegem, Belgium. jan.van.den.brande@uza.be
authors.forename: J
authors.initials: J
authors.lastname: Van den Brande
authors.forename: P
authors.initials: P
authors.lastname: Schöffski
authors.forename: J H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: A D
authors.initials: AD
authors.lastname: Roth
authors.forename: F
authors.initials: F
authors.lastname: Duffaud
authors.forename: K
authors.initials: K
authors.lastname: Weigang-Köhler
authors.forename: F
authors.initials: F
authors.lastname: Reinke
authors.forename: J
authors.initials: J
authors.lastname: Wanders
authors.forename: R F
authors.initials: RF
authors.lastname: de Boer
authors.forename: J B
authors.initials: JB
authors.lastname: Vermorken
authors.forename: P
authors.initials: P
authors.lastname: Fumoleau
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid