{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T09:00:19Z","timestamp":1791018019259,"version":"4.1.0"},"reference-count":55,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2008,3,20]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Regulation of epidermal growth factor receptor (EGFR) signaling pathways may play a relevant role in determining the activity of cetuximab therapy in patients with metastatic colorectal cancer (MCRC). We investigated possible associations between genetic variants and clinical outcomes of MCRC patients treated with cetuximab-irinotecan salvage therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>Patients who underwent cetuximab-irinotecan salvage therapy after disease progression during or after first-line bolus\/infusional fluorouracil, leucovorin, and oxaliplatin chemotherapy and a second-line irinotecan-based regimen were considered eligible for analysis of polymorphisms with putative influence on cetuximab-related pathways. Epidermal growth factor (EGF) 61A&gt;G, EGF receptor (EGFR) 216G&gt;T, EGFR 497G&gt;A, EGFR intron-1 (CA)<jats:sub>n<\/jats:sub>dinucleotide short (S)\/long (L) variant, cyclin-D1 870A&gt;G, immunoglobulin-G fragment-C receptors RIIIa 158G&gt;T, and RIIa 131G&gt;A were studied for a possible association with overall survival (OS) as the primary end point. Additional analyses were addressed at possible associations among polymorphisms and EGFR expression, toxicity, and response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 110 assessable patients, significant association with favorable OS was observed for EGFR intron-1 S\/S and EGF 61 G\/G genotypes. In the multivariate model, EGFR intron-1 S\/S and EGF 61 G\/G genotypes showed a hazard ratio of 0.41 (95% CI, 0.21 to 0.78; P = .006) and 0.44 (95% CI, 0.23 to 0.84; P = .01), respectively. EGFR intron-1 S\/S carriers showed more frequent G2-G3 skin toxicity (\u03c7<jats:sup>2<\/jats:sup>test = 12.7; P = .001) and treatment response (\u03c7<jats:sup>2<\/jats:sup>test = 9.45; P = .008) than EGFR intron-1 L\/L carriers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Although additional studies are required for confirmation, our findings could optimize the use of cetuximab in MCRC patients.<\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2007.12.4602","type":"journal-article","created":{"date-parts":[[2008,3,18]],"date-time":"2008-03-18T22:23:52Z","timestamp":1205879032000},"page":"1427-1434","source":"Crossref","is-referenced-by-count":105,"title":["Pharmacogenetic Profiling for Cetuximab Plus Irinotecan Therapy in Patients With Refractory Advanced Colorectal Cancer"],"prefix":"10.1200","volume":"26","author":[{"given":"Francesco","family":"Graziano","sequence":"first","affiliation":[{"name":"From the Medical Oncology Unit, Hospital of Pesaro, Pesaro; Institute of Biochemistry \u201cG. Fornaini,\u201d and Institute of Biotechnology, University of Urbino, Urbino; Medical Oncology Unit, Azienda USL-6 Livorno, Livorno; University of Pisa, Istituto Toscano Tumori, Pisa; Medical Oncology Unit, University Campus Biomedico, Rome; Medical Oncology Unit, Hospital of Fermo, Fermo; Medical Oncology Unit, Hospital of Macerata, Macerata; Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; and Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annamaria","family":"Ruzzo","sequence":"additional","affiliation":[{"name":"From the Medical Oncology Unit, Hospital of Pesaro, Pesaro; Institute of Biochemistry \u201cG. Fornaini,\u201d and Institute of Biotechnology, University of Urbino, Urbino; Medical Oncology Unit, Azienda USL-6 Livorno, Livorno; University of Pisa, Istituto Toscano Tumori, Pisa; Medical Oncology Unit, University Campus Biomedico, Rome; Medical Oncology Unit, Hospital of Fermo, Fermo; Medical Oncology Unit, Hospital of Macerata, Macerata; Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; and Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fotios","family":"Loupakis","sequence":"additional","affiliation":[{"name":"From the Medical Oncology Unit, Hospital of Pesaro, Pesaro; Institute of Biochemistry \u201cG. 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Fornaini,\u201d and Institute of Biotechnology, University of Urbino, Urbino; Medical Oncology Unit, Azienda USL-6 Livorno, Livorno; University of Pisa, Istituto Toscano Tumori, Pisa; Medical Oncology Unit, University Campus Biomedico, Rome; Medical Oncology Unit, Hospital of Fermo, Fermo; Medical Oncology Unit, Hospital of Macerata, Macerata; Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; and Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Santini","sequence":"additional","affiliation":[{"name":"From the Medical Oncology Unit, Hospital of Pesaro, Pesaro; Institute of Biochemistry \u201cG. 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Fornaini,\u201d and Institute of Biotechnology, University of Urbino, Urbino; Medical Oncology Unit, Azienda USL-6 Livorno, Livorno; University of Pisa, Istituto Toscano Tumori, Pisa; Medical Oncology Unit, University Campus Biomedico, Rome; Medical Oncology Unit, Hospital of Fermo, Fermo; Medical Oncology Unit, Hospital of Macerata, Macerata; Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; and Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renato","family":"Bisonni","sequence":"additional","affiliation":[{"name":"From the Medical Oncology Unit, Hospital of Pesaro, Pesaro; Institute of Biochemistry \u201cG. Fornaini,\u201d and Institute of Biotechnology, University of Urbino, Urbino; Medical Oncology Unit, Azienda USL-6 Livorno, Livorno; University of Pisa, Istituto Toscano Tumori, Pisa; Medical Oncology Unit, University Campus Biomedico, Rome; Medical Oncology Unit, Hospital of Fermo, Fermo; Medical Oncology Unit, Hospital of Macerata, Macerata; Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy; and Cancer..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Torresi","sequence":"additional","affiliation":[{"name":"From the Medical Oncology Unit, Hospital of Pesaro, Pesaro; Institute of Biochemistry \u201cG. 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