Epidermal growth factor receptor gene copy number, K-ras mutation and pathological response to preoperative cetuximab, 5-FU and radiation therapy in locally advanced rectal cancer

Carmelo Bengala, S. Bettelli, F. Bertolini, S. Salvi, S. Chiara, C. Sonaglio, L. Losi, N. Bigiani, G. Sartori, C. Dealis, N. Malavasi, R. D'Amico, G. Luppi, B. Gatteschi, A. Maiorana, P. F. Conte

Research output: Contribution to journalArticle

Abstract

Background: Cetuximab improves activity of chemotherapy in metastatic colorectal cancer (mCRC). Gene copy number (GCN) of epidermal growth factor receptor (EGFR) has been suggested to be a predictive factor of response to cetuximab in patients (pts) with mCRC; on the contrary, K-ras mutation has been associated with cetuximab resistance. Patients and methods: We have conducted a phase II study with cetuximab administered weekly for 3 weeks as single agent and then with 5-fluorouracil and radiation therapy as neo-adjuvant treatment for locally advanced rectal cancer (LARC). EGFR immunohistochemistry expression, EGFR GCN and K-ras mutation were evaluated on diagnostic tumor biopsy. Dworak's tumor regression grade (TRG) was evaluated on surgical specimens. Results: Forty pts have been treated; 39 pts are assessable. TRG 3 and 4 were achieved in nine (23.1%) and three pts (7.7%) respectively; TRG 3-4 rate was 55% and 5.3% in case of high and low GCN, respectively (P 0.0016). Pts with K-ras mutated tumors had lower rate of high TRG: 11% versus 36.7% (P 0.12). In pts with wild-type K-ras, TRG 3-4 rate was 58.8% versus 7.7% in case of high or low GCN, respectively (P 0.0012). Conclusions: In pts with LARC, EGFR GCN is predictive of high TRG to cetuximab plus 5-FU radiotherapy. Moreover, our data suggest that a wild-type K-ras associated with a high EGFR GCN can predict sensitivity to cetuximab-based treatment.

Original languageEnglish
Pages (from-to)469-474
Number of pages6
JournalAnnals of Oncology
Volume20
Issue number3
DOIs
Publication statusPublished - 2009

Keywords

  • Cetuximab
  • EGFR
  • KRAS
  • Neoadjuvant chemo-radiotherapy
  • Rectal cancer

ASJC Scopus subject areas

  • Oncology
  • Hematology

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