EGFR ligands as pharmacodynamic biomarkers in metastatic colorectal cancer patients treated with cetuximab and irinotecan
| Autor: | Paola Orlandi, Lisa Salvatore, Cristiana Lupi, Teresa Di Desidero, Guido Bocci, Antonello Di Paolo, Anna Fioravanti, Fulvio Basolo, Bastianina Canu, Elisa Sensi, Romano Danesi, Fotios Loupakis, Alfredo Falcone, Gianluca Masi, Gabriella Fontanini, Chiara Cremolini, Carlotta Antoniotti, Marta Schirripa, Pinuccia Faviana |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Adult
Male Proto-Oncogene Proteins B-raf Oncology Cancer Research medicine.medical_specialty Colorectal cancer Antibodies Monoclonal Humanized Ligands medicine.disease_cause Irinotecan Disease-Free Survival Proto-Oncogene Proteins p21(ras) Amphiregulin Epidermal growth factor Proto-Oncogene Proteins Internal medicine Antineoplastic Combined Chemotherapy Protocols cetuximab Biomarkers Tumor Humans Medicine Pharmacology (medical) Prospective Studies Progression-free survival Epidermal growth factor receptor Neoplasm Metastasis neoplasms Aged Aged 80 and over biology Cetuximab business.industry Middle Aged medicine.disease digestive system diseases ErbB Receptors ras Proteins biology.protein Camptothecin Female KRAS Colorectal Neoplasms business medicine.drug |
| Popis: | This study was conducted to describe the modulation of plasma epidermal growth factor receptor (EGFR) ligands in EGFR-positive metastatic colorectal cancer (mCRC) patients during treatment with cetuximab and irinotecan and to explore the clinical implication of plasma levels' variations as potential biomarkers of benefit. Plasma amphiregulin (AR), epidermal growth factor (EGF), transforming growth factor-α, and heparin binding-EGF were assessed by ELISA in 45 chemorefractory mCRC patients, treated with cetuximab and irinotecan. Plasma levels were measured before and 1 h after the first administration of cetuximab, before and 1 h after the second administration, and before the third and the fifth cycles. KRAS and BRAF mutational status were determined. EGFR ligands' levels were differently modulated according to tumor KRAS and BRAF mutational status. In KRAS wild-type patients (n = 34), AR and EGF early increased and higher increases were significantly associated with worse clinical outcome. By adopting a specific cut-off value, patients with higher levels of AR 1 h after the first administration had significantly worse response rate, progression free survival, and overall survival. This hypothesis-generating study shows that EGFR ligands are significantly modulated by cetuximab plus irinotecan according to KRAS and BRAF mutational status, and they warrant further investigation as pharmacodynamic markers of resistance to anti-EGFRs. |
| Databáze: | OpenAIRE |
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