Phase II trial of 5-fluorouracil (5FU)/leucovorin (LV), irinotecan, and oxaliplatin (FOLFOXIRI) plus cetuximab in patients with metastatic colorectal cancer (mCRC).

e14027 Background: To evaluate the safety and efficacy of cetuximab combined with 5FU/LV, irinotecan and oxaliplatin (FOLFOXIRI) as initial treatment for patients with unresectable, KRAS wt mCRC. Methods: Primary end point was overall response rate while secondary endpoints were the percentage of R0 secondary resection, time to tumor progression (TTP), median overall survival (mOS) and the safety profile of the combination. From July 2007 to August 2010, thirty patients < 70 years old with PS (ECOG) 0-1 and unresectable, KRAS wt mCRC were enrolled in the study. The patients were treated with cetuximab 500 mg/m2 followed by the administration of FOLFOXIRI (d1: Irinotecan 150 mg/m2; d2 L-OHP 65 mg/m2; d2-3 LV 200 mg/m2; and d3? 5-FU 400 mg/m2 as i.v. bolus and 600 mg/m2as 22 h i.v. continuous infusion). The treatment was administered every 2 weeks. Results: The median age of the patients was 64, 16 (53%) were male and 16 of them had disease limited to the liver. Main toxic effects included grade 3-4 neutropenia (23%), grade 3/4 diarrhea (53%), grade 2-3 skin rash (43%) and grade 2-3 neurotoxicity (18%). One toxic death was observed during the study due to diarrhea and sepsis in a female patient with peritoneal disease. Four (13%) complete and seventeen (57%) partial responses were achieved (ORR: 70%; 95% confidence interval: 55% to 86%), whereas 8 (27%) patients had stable disease. Secondary R0 liver resection was performed in 9 patients (30% of the total population, 57% of the patients with liver limited disease). After a median follow-up of 15.1 months the median TTP was 11 months, the mOS had not yet been reached, and the probability of 1-year survival was 53.4%. Conclusions: The combination of cetuximab plus FOLFOXIRI is highly active with significantly high percentage of R0 secondary resection. Due to the high incidence of diarrhea the treatment should be administered in selective patients and mainly in those with liver limited disease.