Nuclear factor-kB tumor expression predicts response and survival in irinotecan-refractory metastatic colorectal cancer treated with cetuximab-irinotecan therapy

Purpose NF- kB expression has been shown to be responsible for resistance to antineoplastic agents and it also plays a part in the activation of the epidermal growth factor receptor downstream signaling pathway in colorectal tumors. The aim of our analysis was to investigate a correlation between NF- kB expression, response rate, time to progression, and survival in advanced colorectal cancer patients receiving cetuximab and irinotecan. Patients and Methods We analyzed retrospectively the immunoreactivity for NF- kB in irinotecan- refractory patients receiving cetuximab and irinotecan. Results Seventy- six patients were analyzed. Cetuximab and irinotecan were administered as second- line chemotherapy in 19 patients and after >= two lines of chemotherapy in the remaining 57 patients. We observed a partial response ( PR) in 16 patients for an overall response rate of 24%. Thirty- two patients ( 48%) experienced progressive disease; median time to progression ( TTP) was 3.6 months and median overall survival was 10.3 months. NF- kB was positive in 46 patients ( 60%). All main clinical characteristics were well balanced between NF-kB-positive and NF-kB-negative patients. The response rate was 10% ( four PRs) versus 48% ( 12 PRs; P =.0007) in NF-kB-positive and NF-kB-negative tumors, respectively. Median TTP in NF-kB-positive patients was 3 v 6.4 months in the remaining patients ( P =.021). Median overall survival was 9.5 v 15.8 months for NF-kB-positive and NF-kB-negative patients, respectively ( P =.036) Conclusion The difference in median TTP, overall survival, and response rate seem to confirm that NF- kB may play a crucial role in predicting the efficacy of cetuximab and irinotecan in advanced colorectal tumors.