ABSTRACT
BACKGROUND: Cetuximab is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor and is able to reverse the resistance to irinotecan in patients with metastatic colorectal cancer (mCRC). This phase II trial evaluates the safety and efficacy of cetuximab combined with capecitabine and oxaliplatin (CAPOX) in the treatment of patients with mCRC progressing under oxaliplatin-based chemotherapy. PATIENTS AND TREATMENT: Forty patients with mCRC were treated with cetuximab (loading dose 400 mg/m(2) and then 250 mg/m(2) i.v. weekly) in combination with CAPOX (d(1): L-OHP 85 mg/m(2) and d(1-7) capecitabine 2000 mg/m(2) every 2 weeks). Thirty-one (77.5%) and nine (22.5%) patients had oxaliplatin-refractory and -resistant disease, respectively; in addition, 32 (80%) patients had also progressed on prior irinotecan-based chemotherapy. RESULTS: One hundred and thirty-four cycles were administered (median of four cycles per patient). Main toxic effects included grade 3-4 neutropenia (12.5%), grade 3/4 diarrhea (7.5%), grade 3 fatigue (2.5%), and grade 2-3 neurotoxicity (22.5%). One (2.5%) complete and seven (17.5%) partial responses were achieved [overall objective response rate (ORR): 20%; 95% confidence interval (CI): 9% to 32%)], whereas 11 (27.5%) patients had stable disease [disease control rate (DCR): 47.5%; 95% CI: 30.2% to 64.5%]. The ORR and DCR were 18.7% and 46.8%, respectively, in patients with oxaliplatin-refractory disease. The median time to tumor progression was 3 months, the median survival 10.7 months and the probability of 1-year survival rate 53.4%. CONCLUSIONS: The combination of cetuximab plus CAPOX is safe and has a promising activity in patients with mCRC refractory or resistant to oxaliplatin.