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Nuclear Factor-kB Tumor Expression Predicts Response and Survival in Irinotecan-Refractory Metastatic Colorectal Cancer Treated With Cetuximab-Irinotecan Therapy

Mario Scartozzi, Italo Bearzi, Chiara Pierantoni, Alessandra Mandolesi, Fotios Loupakis, Alberto Zaniboni, Vincenzo Catalano, Antonello Quadri, Fausto Zorzi, Rossana Berardi, Tommasina Biscotti, Roberto Labianca, Alfredo Falcone, Stefano Cascinu

From the Clinica di Oncologia Medica and Anatomia Patologica, Azienda Ospedaliera Ospedali Riuniti-Università Politecnica delle Marche, Ancona; Oncologia Medica, Ospedale Civico, Livorno - Università degli Studi di Pisa, Pisa; Oncologia Medica and Anatomia Patologica Casa di Cura Poliambulanza, Brescia; Oncologia Medica, AO San Salvatore, Pesaro; and Oncologia Medica, Ospedali Riuniti, Bergamo, Italy

Address reprint requests to Stefano Cascinu, MD, Clinica di Oncologia Medica, AO Ospedali Riuniti, Università Politecnica delle Marche, Via Conca, 60020 Ancona, Italy; e-mail: cascinu{at}yahoo.com

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.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Related Correspondence

• Activated NF-kB in Colorectal Cancer: Predictive or Prognostic Factor?
  Giovanni Brandi, Maria A. Pantaleo, Guido Biasco, and Paola Paterini
  JCO 2008 26: 1388-1389 [Full Text]

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