Phase II study of sequential methotrexate and 5-fluorouracil chemotherapy against peritoneally disseminated gastric cancer with malignant ascites: a report from the Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group, JCOG 9603 Trial.

BACKGROUND: The efficacy of systemic chemotherapy against peritoneal dissemination from advanced gastric cancer (AGC) remains unclear, because the peritoneal dissemination was not defined as a measurable lesion in conventional phase II studies. In this study, we evaluated the efficacy and toxicity of sequential MTX and 5FU therapy (MF) in chemotherapy-naive patients with AGC accompanied by malignant ascites in a phase II setting. METHODS: The treatment schedule comprised weekly administration of MTX (100 mg/m2, i.v. bolus) followed by 5FU (600 mg/m2, i.v. bolus) with a 3 h interval. Leucovorin rescue (10 mg/m2 every 6 h, for a total of six times) was commenced 24 h after MTX administration. RESULTS: Thirty-seven chemotherapy-naive patients with AGC presenting with malignant ascites were enrolled in this trial. The median age was 60 years (range, 25-74 years) and most patients (86%) had a performance status of 0-1. In total, 355 administrations of the sequential MTX/5FU therapy were performed. Major toxicity consisted of myelosuppression and gastrointestinal toxicity. Grade 4 neutropenia occurred in 10.8% of the patients. The overall objective response rate was 5.7% (two partial responses in 35 patients; 95% confidence interval: 0.7-19.2%). However, the response rate of ascites was 35.1% (complete disappearance in three patients and apparent decrease in 10 patients; 95% confidence interval: 20.2-52.5%). CONCLUSIONS: Sequential MTX/5FU therapy is effective against AGC with malignant ascites with acceptable toxicity and warrants further investigations in a phase III setting.

A preliminary study of preoperative chemotherapy combining irinotecan and cisplatin in patients with gastric cancer with unresectable para-aortic lymph node metastases.

BACKGROUND: A high response rate has been reported for chemotherapy combining irinotecan (CPT-11) and cisplatin (CDDP) against advanced gastric cancer. The strong anti-tumor activity of this regimen makes it very attractive as a preoperative chemotherapy. We conducted a preliminary study on preoperative chemotherapy with this regimen in patients with unresectable gastric cancer with para-aortic lymph node metastases to evaluate the feasibility of it as a treatment strategy. METHODS: Patients with unresectable para-aortic lymph node metastasis without distant hematogenous metastasis (H0, M0 and M1 LYM) and peritoneal dissemination (P0) were eligible for entry. The preoperative chemotherapy consisted of at least three cycles of CPT-11 (70 mg/m(2)) on days 1 and 15 and CDDP (80 mg/m(2)) on day 15, repeated every 4-6 weeks. Chemotherapy was followed by surgery with extended lymph node dissection in patients who achieved complete or partial responses and whose cancers were judged to be resectable. RESULTS: Six patients were entered into the study. In total, 18 cycles of chemotherapy were performed and five patients received at least three cycles. Objective partial responses were achieved in four patients. The major toxicities in the chemotherapy were neutropenia and diarrhea, but these were clinically acceptable. Four patients underwent surgery after the chemotherapy, and macroscopically complete resections with extended lymph node dissection were achieved in two patients. There were no therapy-related deaths. We found no pathological complete responses, but observed a definite histopathological effect caused by the chemotherapy in surgical specimens. The median survival time of all patients was 12 months. The longest survival without relapse is >6 years from the start of therapy. CONCLUSIONS: We conclude that preoperative chemotherapy with CPT-11/CDDP therapy is feasible in patients with advanced gastric cancer and that the regimen is safe when followed by surgery. Further clinical studies with larger numbers of patients are warranted to evaluate the efficacy of this strategy.