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..

Bengala, C; Bettelli, Stefania Raffaella; Salvi, S; Chiara, S; Sonaglio, C; Losi, Lorena; Bigiani, N; Sartori, G; Dealis, Cristina; Malavasi, Norma; D'Amico, Roberto; Luppi, G; Gatteschi, B; Maiorana, Antonino; Conte, Pierfranco

doi:10.1093/annonc/mdn647

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.PMID: 19095777 [PubMed - indexed for MEDLINE]Related articlesNeoadjuvant treatment with single-agent cetuximab followed by 5-FU, cetuximab, and pelvic radiotherapy: a phase II study in locally advanced rectal cancer. Int J Radiat Oncol Biol Phys. 2009 Feb 1; 73(2):466-72. Epub 2008 Nov 10. [Int J Radiat Oncol Biol Phys. 2009]Expression of epiregulin and amphiregulin and K-ras mutation status predict disease control in metastatic colorectal cancer patients treated with cetuximab. J Clin Oncol. 2007 Aug 1; 25(22):3230-7. [J Clin Oncol. 2007]A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment. BMC Cancer. 2008 Jun 10; 8:169. Epub 2008 Jun 10. [BMC Cancer. 2008]Review[The RAS paradox of the EGFR-targeted therapy in colorectal cancer] Magy Onkol. 2008 Jun; 52(2):185-91. [Magy Onkol. 2008]ReviewAssessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer. Lancet Oncol. 2008 Oct; 9(10):962-72. Epub 2008 Sep 17. [Lancet Oncol. 2008]» See reviews... | » See all... Patient Drug InformationFluorouracil (Adrucil®) Your doctor has ordered the drug fluorouracil to help treat your illness. The drug is given by injection into a vein. Source: AHFS Consumer Medication Information

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. / Bengala, C; Bettelli, Stefania Raffaella; Salvi, S; Chiara, S; Sonaglio, C; Losi, Lorena; Bigiani, N; Sartori, G; Dealis, Cristina; Malavasi, Norma; D'Amico, Roberto; Luppi, G; Gatteschi, B; Maiorana, Antonino; Conte, Pierfranco. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - STAMPA. - 20:3(2009), pp. 469-474. [10.1093/annonc/mdn647]