Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205).
OBJECTIVE
To compare fluorouracil (FU) alone with FU plus cisplatin (FP) and with uracil and tegafur plus mitomycin (UFTM) for patients with advanced gastric cancer in a prospective, randomized, controlled trial.


METHODS
A total of 280 patients with advanced gastric cancer were randomly allocated and analyzed for survival, response, and toxicity. The survival curves were compared between groups by log-rank test on an intent-to-treat basis.


RESULTS
At the interim analysis, the UFTM arm showed a significantly inferior survival with higher incidences of hematologic toxic effects than did control arm FU alone, and the registration to UFTM was terminated. Both investigational regimens, FP and UFTM, had a significantly higher incidence of hematologic toxic effects than FU alone, although the effects were manageable. The overall response rates of the FU-alone, FP, and UFTM arms were 11%, 34%, and 9%, respectively. The median progression-free survival was 1.9 months with FU alone, 3.9 months with FP, and 2.4 months with UFTM, respectively. Although FP demonstrated a higher response rate (P <.001) and longer progression-free survival than did FU alone (P <.001), no differences in overall survival were observed between the arms. The median survival times and 1-year survival rates were 7.1 months and 28% with FU, 7.3 months and 29% with FP, and 6.0 months and 16% with UFTM, respectively.


CONCLUSIONS
Neither investigational regimen, FP nor UFTM, showed a survival advantage as compared with FU alone. FU alone will remain a reference arm in our future trial for advanced gastric cancer.
Ohtsu
Atsushi
A
Division of Gastrointestinal Oncology/Digestive Endoscopy, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. aohtsu@east.ncc.go.jp
Shimada
Yasuhiro
Y
Shirao
Kuniaki
K
Boku
Narikazu
N
Hyodo
Ichinosuke
I
Saito
Hiroshi
H
Yamamichi
Noboru
N
Miyata
Yoshinori
Y
Ikeda
Nobumasa
N
Yamamoto
Seiichiro
S
Fukuda
Haruhiko
H
Yoshida
Shigeaki
S
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015996:Survival Rate; D005641:Tegafur / Q000627:therapeutic use; D014498:Uracil / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D005641:Tegafur; D016685:Mitomycin; D014498:Uracil; D002945:Cisplatin; D005472:Fluorouracil