Phase II trial with S-1 in chemotherapy-naïve patients with gastric cancer. A trial performed by the EORTC Early Clinical Studies Group (ECSG).
S-1 is a new oral fluorinated pyrimidine derivate, in which the oral 5-fluorouracil (5-FU) prodrug, tegafur, was combined with two 5-FU-modulating substances, 5-chloro-2,4-dihydroxypyridine (gimeracil), and potassium oxonate (oteracil), at a molar ratio of 1:0.4:1. The final mechanism of action is exerted by 5-FU. The present study is the first European phase II trial of S-1 in gastric cancer. The primary study objectives were the safety, toxicity and activity of S-1 in non-pretreated patients with gastric cancer. The secondary objective was the duration of response. Patients had to have histologically- or cytologically-verified metastatic or locally advanced, unresectable gastric cancer; S-1 was administered orally twice daily at 40, then 35 mg/m(2) for 28 days every 5 weeks. The starting dose of 40 mg/m(2) was found to be intolerable due to significant non-haematological toxicity, and this dose was rapidly reduced to 35 mg/m(2) twice daily. Of the 7 patients enrolled at the 40 mg/m(2) level, only 3 were evaluable. At 35 mg/m(2), a response rate of 26.1% (95% Confidence Interval (CI) 12.0-45.1%) in 23 enrolled patients, and 31.6% (C.I. 14.7-53.0%) in 19 evaluable patients according to an independent radiology review, was found. The median duration of response at 35 mg/m(2) (6 patients) was 223 days (range, 108-828 days), and of stable disease was 111 days (range 68-411 days). S-1 can be administered with an acceptable safety and toxicity in European patients at a dose of 35 mg/m(2) days 1 - 28 every 5 weeks and is associated with a moderate response rate similar to the results achieved with other fluoropyrimidines.
Chollet
P
P
Department of Medical Oncology, Centre Jean-Perrin, 58 Rue Montalembert, F-63011, Cedex 1, Clermont-Ferrand, France. recherche.clinique@cjp.u-clermont1.fr
Schöffski
P
P
Weigang-Köhler
K
K
Schellens
J H M
JH
Cure
H
H
Pavlidis
N
N
Grünwald
V
V
De Boer
R
R
Wanders
J
J
Fumoleau
P
P
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid