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.
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/m(2), i.v. bolus), followed by 5-FU (600 mg/m(2), i.v. bolus) 3 h after MTX administration. Leucovorin rescue therapy (six doses of 10 mg/m(2), 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.
Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan.
Tetsuya
T
Hamaguchi
Kuniaki
K
Shirao
Noboru
N
Yamamichi
Ichinosuke
I
Hyodo
Wasaburo
W
Koizumi
Shigeki
S
Seki
Tetsuri
T
Imamura
Hisanobu
H
Honma
Atsushi
A
Ohtsu
Narikazu
N
Boku
Toshikazu
T
Mukai
Seiichiro
S
Yamamoto
Haruhiko
H
Fukuda
Shigeaki
S
Yoshida
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007275:Injections, Intravenous; D007564:Japan; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000139:chemically induced; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000627:therapeutic use
D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D014803:Vitamin B Complex; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate