Japanese Journal of Clinical Oncology Advance Access originally published online on May 30, 2008
Japanese Journal of Clinical Oncology 2008 38(6):432-437; doi:10.1093/jjco/hyn043
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© The Author (2008). Published by Oxford University Press. All rights reserved
A Phase II Study of Sequential Methotrexate and 5-fluorouracil Chemotherapy in Previously Treated Gastric Cancer: A Report from the Gastrointestinal Oncology Group of the Japan Clinical Oncology Group, JCOG 9207 Trial
1 Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo
2 Department of Surgery, Fukui Prefectural Hospital, Fukui
3 Department of Internal Medicine, National Hospital Organization, Shikoku Cancer Center, Ehime
4 Department of Internal Medicine, Kitasato University East Hospital, Kanagawa
5 Department of Internal Medicine, Saku Central Hospital, Nagano
6 Department of Gastroenterology, Sapporo-Kosei General Hospital, Hokkaido
7 Department of Gastroenterology, National Hospital Organization, Hokkaido Cancer Center, Hokkaido
8 Division of Gastrointestinal Oncology/Digestive Endoscopy, National Cancer Center Hospital East, Chiba
9 Department of Internal Medicine, Kure Kyosai Hospital, Hiroshima
10 Cancer Information Services and Surveillance Division, Center for Cancer Control and Information Services, National Cancer Center, Tokyo
11 Clinical Trials and Practice Support Division, Center for Cancer Control and Information Services, National Cancer Center, Tokyo, Japan
12 Director, National Cancer Center Hospital East, Chiba
13 Department of Medical Oncology, Oita University, Faculty of Medicine, Oita, Japan
For reprints and all correspondence: Kuniaki Shirao, Department of Medical Oncology, Oita University, Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-city, Oita 879-5593, Japan. E-mail: kshirao{at}med.oita-u.ac.jp
Received February 26, 2008; accepted May 7, 2008
Objective: As prognosis of advanced gastric cancer is still poor, a standard regimen after first-line fluorouracil (FU)-based chemotherapy has not yet been established. Therefore, we conducted a phase II study to evaluate the efficacy and toxicity of sequential treatment with methotrexate (MTX) and also 5-FU as second-line chemotherapy in patients with advanced gastric cancer.
Methods: Treatment consisted of weekly doses of MTX (100 mg/m2, i.v. bolus), followed by 5-FU (600 mg/m2, i.v. bolus) 3 h after MTX administration. Leucovorin rescue therapy (six doses of 10 mg/m2, given at 6-h intervals) was commenced 24 h after a treatment with MTX. The primary endpoint was the response rate.
Results: Between December 1992 and June 1995, 56 patients were registered in this study and one was ineligible. All registered patients were included in all analyses. The median age of the patients was 60 years (20–75 years). Most patients (75%) had a performance status of 0 or 1, and 51 (90%) received 5-FU-based chemotherapy as first-line treatment. The major adverse events were myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 6.3% of the patients. The overall objective response rate was 9.0% [five partial responses among 56 patients, 95% confidence interval (CI): 3.0–20%]. The median overall survival time was 237 days, and the 1-year survival proportion was 21.4%.
Conclusions: Sequential MTX/5-FU therapy provides good survival outcomes with tolerable toxicity despite a limited response in patients with previously treated advanced gastric cancer. This regimen is now being evaluated in a randomized study in patients with pretreated advanced gastric cancer, by the Japan Clinical Oncology Group.
Key Words: methotrexate • 5-fluorouracil • gastric cancer • second-line chemotherapy