Background: Scientific data provide today the evidence that secondary K-RAS mutations do not occur during anti-EGFR therapy in CRC patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. Patients and Methods: we enrolled 39 irinotecan refractory patients who had a clinical benefit after a line of Cetuximab plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were re-treated with the same Cetuximab plus Irinotecan based therapy. Results: Median number of therapeutic lines before accrual was 4. Median interval time between last cycle of first cetuximab-based therapy and first cycle of the retreatment was 6 months. Overall response rate was 53.8% with 19 partial responses (48.7%) and 2 complete responses (5.1%). Disease stabilization was obtained in 35.9% of patients and progression in 4 patients (10.2%). Median time to progression was 6.6 months. The correlation between skin toxicity during first cetuximab therapy and during cetuximab rechallenge was significant (p= .01). Conclusions: Rechallenge with the same cetuximab-based therapy may achieve a new important clinical benefit further delaying the progression of disease and improving the therapeutic options
