Phase II trial of irinotecan plus oxaliplatin and 5-fluorouracil/leucovorin in patients with untreated metastatic gastric adenocarcinoma

Background: This nonrandomized open label phase II study evaluated the efficacy and safety of FOLFOXIRI in metastatic or recurrent gastric cancer patients. Patients and methods: Patients with histologically proven, metastatic gastric adenocarcinoma, aged 18–70 years, performance status zero to two, no prior chemotherapy, and with signed written informed consent were eligible. Treatment consisted of irinotecan 150 mg/m2 day 1, oxaliplatin 85 mg/m2 day 1, leucovorin 100 mg/m2 day 1, and 5-fluorouracil 2000 mg/m2 as a 48-h continuous infusion starting on day 1, which was repeated every 2 weeks. Results: From August 2004 to August 2005, 48 patients were prospectively enrolled. The median age was 54 years (24–69). In total, 386 cycles were administered with a median of nine cycles per patient (range 1–12 cycles) and 45 of 48 patients were assessable for treatment response. An independent review of tumor responses resulted in overall response rate of 66.7% (95% confidence interval = 53.4% to 80.0%) by intent-to-treat analysis with one complete response and 31 partial responses. The median survival of all patients was 14.8 months and the median time to progression was 9.6 months. Most common grade 3/4 toxic effects were neutropenia (12% of all cycles) and emesis (8% of all cycles). Grade 2 peripheral neuropathy occurred in five patients. One (2%) patient had severe tumor bleeding and five (10%) patients experienced grade 3 diarrhea. Conclusions: The modified FOLFOXIRI combination chemotherapy showed a very promising preliminary antitumor activity and was generally well tolerated as a first-line treatment of patients with metastatic gastric cancer.