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 efficacyof 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 recurrentadenocarcinoma of the gastroesophageal junction (GEJ) or stomach wereentered onto this study. Previous chemotherapy for metastatic diseasewas not allowed. Treatment consisted of repeated 6-week cyclescomprising CPT-11 125 mg/m² intravenously (i.v.) followedimmediately by LCV 20 mg/m² i.v. and 5-FU 500mg/m² i.v., all given weekly for four weeks followed by atwo-week rest.Results:Thirty-eight patients wereenrolled and 36 eligible patients received protocol therapy. Grade3–5 toxicities consisted primarily of neutropenia (36%) anddiarrhea (28%). Neutropenic infection was observed in 14%of patients, with 3 (8%) dying of neutropenic sepsis. The overallresponse rate was 22% (95% confidence interval [CI]8.5% to 35.5%). Median survival was 7.6 months, and mediantime to progression was 4.4 months.Conclusion:Thisweekly regimen of CPT-11 with bolus 5-FU/LCV is active in patients withadvanced adenocarcinomas of the stomach or gastroesophageal junction.While rates of grade 3–4 neutropenia and diarrhea were similar tothose observed historically in patients receiving this regimen forcolorectal cancer, neutropenic fever/sepsis appeared to be morefrequent, and dose modifications were substantial. Future trials of thiscombination in patients with gastric cancer should decrease the absolutestarting drug doses and/or employ altered scheduling that betteraccommodates the pattern of toxicity.