Phase II study of gefitinib, fluorouracil, leucovorin, and oxaliplatin therapy in previously treated patients with metastatic colorectal cancer

Purpose To investigate the gefitinib, fluorouracil (FU), leucovorin, and oxaliplatin regimen (IFOX) in previously treated patients with metastatic colorectal cancer. Patients and Methods Eligible patients had stage IV colorectal adenocarcinoma and had demonstrated progression or intolerance to a prior chemotherapy regimen not including oxaliplatin. Each cycle consisted of 14 days. Cycle I consisted of oxaliplatin 85 mg/m(2) intravenously (IV) during 2 hours on day 1, hours 0 to 2; leucovorin 200 mg/m(2) IV on days I and 2, hours 0 to 2; FU 400 mg/m(2) IV push on days I and 2; and FU 600 mg/m(2) IV on days I and 2, hours 2 to 24 (FOLFOX-4). All subsequent cycles consisted of FOLFOX-4 with gefitinib at 500 mg/d administered orally throughout the 14-day cycle. Results Twenty-seven patients were enrolled onto the study. The median number of prior chemotherapy regimens was two, and 74% of all patients received prior irinotecan. Nine of the 27 patients (33%) and six of the 20 patients (30%) who had prior FU and irinotecan had a partial response by Response Evaluation Criteria in Solid Tumors Group criteria. Median overall survival was 12.0 months. Median event-free survival was 5.4 months. Grade 3 to 4 toxicities included neutropenia (48%), diarrhea (48%), nausea (22%), and vomiting (15%). Conclusion IFOX is an active regimen in patients with previously treated metastatic colorectal adenocarcinoma, demonstrating higher response rates than those reported with FOLFOX-4 alone in a similar patient population.