A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with previously untreated gastric adenocarcinoma

Background: A phase II study testing the safety and efficacy of irinotecan (CPT-11), 5-fluorouracil (5-FU), and leucovorin (LCV) was conducted in patients with advanced gastric adenocarcinomas. Patients and methods: Patients with metastatic or recurrent adenocarcinoma of the gastroesophageal junction (GEJ) or stomach were entered onto this study. Previous chemotherapy for metastatic disease was not allowed. Treatment consisted of repeated 6-week cycles comprising CPT-11 125 mg/m² intravenously (i.v.) followed immediately by LCV 20 mg/m² i.v. and 5-FU 500 mg/m² i.v., all given weekly for four weeks followed by a two-week rest. Results: Thirty-eight patients were enrolled and 36 eligible patients received protocol therapy. Grade 3-5 toxicities consisted primarily of neutropenia (36%) and diarrhea (28%). Neutropenic infection was observed in 14% of patients, with 3 (8%) dying of neutropenic sepsis. The overall response rate was 22% (95% confidence interval [CI] 8.5% to 35.5%). Median survival was 7.6 months, and median time to progression was 4.4 months. Conclusion: This weekly regimen of CPT-11 with bolus 5-FU/LCV is active in patients with advanced adenocarcinomas of the stomach or gastroesophageal junction. While rates of grade 3-4 neutropenia and diarrhea were similar to those observed historically in patients receiving this regimen for colorectal cancer, neutropenic fever/sepsis appeared to be more frequent, and dose modifications were substantial. Future trials of this combination in patients with gastric cancer should decrease the absolute starting drug doses and/or employ altered scheduling that better accommodates the pattern of toxicity.