Gefitinib in combination with 5-fluorouracil (5-FU)/folinic acid and irinotecan in patients with 5-FU/oxaliplatin-refractory colorectal cancer: A phase I/II study of the arbeitsgemeinschaft fur internistische onkologie (AIO)

Background: Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor. It potentiates cytotoxic drug activity in human xenografts. This phase I/II dose-finding study evaluated gefitinib in combination with a 5-fluorouracil (5-FU)/folinic acid (FA)/irinotecan (FOLFIRI-AIO) regimen in patients with metastatic colorectal cancer. Patients and Methods: Patients received gefitinib 250 mg per day, and escalating doses of FOLFIRI-AIO i.v. (dose level (DL) 1: 1600/500/60 mg/m(2); DL2: 1600/500/80 mg/m(2); DL3: 2000/500/80 mg/m(2)) weekly x 6. Dose-limiting toxicity (DLT) was determined in patients who completed 1 cycle of therapy. Results: 13 patients were enrolled. 1 out of 6 patients on DL1 exhibited DLT (acute psychosis), and a total of 7 patients received DL2. Of those, 3 patients had DLT during cycle 1 (nausea/vomiting n = 2; diarrhea n = 1, fatigue n = 2). Recruitment was stopped at this DL because of the unfavorable toxicity profile observed during the first and subsequent treatment cycles (out of 7 patients: nausea/vomiting grade 3 n = 2, diarrhea grade 3 n = 2; fatigue n = 3). Only 1 patient showed a partial remission, and 2 patients experienced stabilization of disease. Conclusions: Dose escalation had to be stopped early because of gastrointestinal toxicity and fatigue. This treatment regimen did not seem advantageous with respect to efficacy in comparison with FOLFIRI-AIO alone.