Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine.
BACKGROUND
Advanced gastric cancer can respond to S-1, an oral fluoropyrimidine. We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer.


METHODS
Patients in Japan with stage II or III gastric cancer who underwent gastrectomy with extended (D2) lymph-node dissection were randomly assigned to undergo surgery followed by adjuvant therapy with S-1 or to undergo surgery only. In the S-1 group, administration of S-1 was started within 6 weeks after surgery and continued for 1 year. The treatment regimen consisted of 6-week cycles in which, in principle, 80 mg of oral S-1 per square meter of body-surface area per day was given for 4 weeks and no chemotherapy was given for the following 2 weeks. The primary end point was overall survival.


RESULTS
We randomly assigned 529 patients to the S-1 group and 530 patients to the surgery-only group between October 2001 and December 2004. The trial was stopped on the recommendation of the independent data and safety monitoring committee, because the first interim analysis, performed 1 year after enrollment was completed, showed that the S-1 group had a higher rate of overall survival than the surgery-only group (P=0.002). Analysis of follow-up data showed that the 3-year overall survival rate was 80.1% in the S-1 group and 70.1% in the surgery-only group. The hazard ratio for death in the S-1 group, as compared with the surgery-only group, was 0.68 (95% confidence interval, 0.52 to 0.87; P=0.003). Adverse events of grade 3 or grade 4 (defined according to the Common Toxicity Criteria of the National Cancer Institute) that were relatively common in the S-1 group were anorexia (6.0%), nausea (3.7%), and diarrhea (3.1%).


CONCLUSIONS
S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer. (ClinicalTrials.gov number, NCT00152217 [ClinicalTrials.gov].).
Sakuramoto
Shinichi
S
Department of Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. sakura@med.kitasato-u.ac.jp
Sasako
Mitsuru
M
Yamaguchi
Toshiharu
T
Kinoshita
Taira
T
Fujii
Masashi
M
Nashimoto
Atsushi
A
Furukawa
Hiroshi
H
Nakajima
Toshifusa
T
Ohashi
Yasuo
Y
Imamura
Hiroshi
H
Higashino
Masayuki
M
Yamamura
Yoshitaka
Y
Kurita
Akira
A
Arai
Kuniyoshi
K
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004338:Drug Combinations; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009367:Neoplasm Staging; D010094:Oxonic Acid / Q000009:adverse effects / Q000627:therapeutic use*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D015996:Survival Rate; D005641:Tegafur / Q000009:adverse effects / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid