Journal of Clinical Oncology, Vol 21, Issue 1
(January), 2003: 54-59
© 2003 American Society for Clinical Oncology
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)
Atsushi Ohtsu,
Yasuhiro Shimada,
Kuniaki Shirao,
Narikazu Boku,
Ichinosuke Hyodo,
Hiroshi Saito,
Noboru Yamamichi,
Yoshinori Miyata,
Nobumasa Ikeda,
Seiichiro Yamamoto,
Haruhiko Fukuda,
Shigeaki Yoshida
From the Division of Gastrointestinal Oncology/Digestive Endoscopy, National Cancer Center Hospital East, Kashiwa; Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo; Department of Internal Medicine, National Shikoku Cancer Center, Matsuyama; Department of Internal Medicine, Yamagata Prefectural Central Hospital, Yamagata; Department of Surgery, Fukui Prefectural Center for Adult Disease, Fukui; Department of Internal Medicine, Saku Central Hospital, Nagano; Department of Internal Medicine, Mitoyo General Hospital, Kagawa; and JCOG Data Center, Cancer Information and Epidemiology Division, National Cancer Center Research Institute, Tokyo, Japan.
Address reprint requests to Atsushi Ohtsu, MD, Division of Gastrointestinal Oncology/Digestive Endoscopy, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, Chiba, 277-8577 Japan; email: aohtsu{at}east.ncc.go.jp.
Purpose: 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.
Patients and 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.
Conclusion: 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.
This work was supported by Grant-in-Aid (5S-1, 8S-1, 11S-3, 11S-4) from the Ministry of Health, Labour, and Welfare, Japan.
Presented in part at the Thirty-fifth Annual Meeting of the American Society of Clinical Oncology, 1999.
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