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Prospective study of EGFR intron 1 (CA)n repeats variants as predictors of benefit from cetuximab and irinotecan in chemo-refractory metastatic colorectal cancer (mCRC) patients.
Loupakis, F; Antoniotti, C; Cremolini, C; Zhang, W; Yang, D; Wakatsuki, T; Bohanes, P; Schirripa, M; Salvatore, L; Masi, G; Ricci, V; Graziano, F; Ruzzo, A; Benhaim, L; Marmorino, F; Ning, Y; El-Khoueiry, R; Falcone, A; Lenz, H-J.
Affiliation
  • Loupakis F; 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
  • Antoniotti C; 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
  • Cremolini C; 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
  • Zhang W; Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • Yang D; Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • Wakatsuki T; Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • Bohanes P; Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • Schirripa M; 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
  • Salvatore L; 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
  • Masi G; 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
  • Ricci V; Unità di Oncologia, Istituto Scientifico San Raffaele, Milano, Italy.
  • Graziano F; Medical Oncology Unit, Hospital of Pesaro, Pesaro, Italy.
  • Ruzzo A; Section of Biochemistry and Molecular Biology, Department of Biomolecular Sciences, University of Urbino, Urbino, Italy.
  • Benhaim L; Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • Marmorino F; 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
  • Ning Y; Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • El-Khoueiry R; Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
  • Falcone A; 1] U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliera-Universitaria Pisana, Pisa, Italy [2] Istituto Toscano Tumori (ITT), Firenze, Italy.
  • Lenz HJ; Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA, USA.
Pharmacogenomics J ; 14(4): 322-7, 2014 Aug.
Article in En | MEDLINE | ID: mdl-24513691
ABSTRACT
The number of CA tandem repeats (CA)n in a highly polymorphic region of EGFR (epidermal growth factor receptor) intron 1 may affect gene transcription; the potential impact of allelic variants on the efficacy of cetuximab in metastatic colorectal cancer (mCRC) patients is debated for long. This study aimed at prospectively estimating the impact of EGFR intron 1 (CA)n variants on clinical outcome in KRAS exon 2 and BRAF wild-type chemo-refractory mCRC patients, receiving cetuximab and irinotecan. Variants presentingpatients were included. No differences in progression-free survival or overall survival were observed between L- and SS genotypes (hazard ratio (HR)=1.00 (95% confidence interval (CI) 0.67-1.50), P=0.991; HR=1.32 (95% CI 0.81-2.16), P=0.261). Exploratory analyses adopting other cutoff values previously described led to similar results. This prospective study did not confirm any previous retrospective finding, reporting a predictive or prognostic effect of EGFR (CA)n repeats allelic variants in chemo-refractory mCRC patients receiving cetuximab and irinotecan.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Camptothecin / Introns / Colorectal Neoplasms / Antibodies, Monoclonal, Humanized / ErbB Receptors Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: Pharmacogenomics J Journal subject: BIOLOGIA MOLECULAR / FARMACOLOGIA Year: 2014 Type: Article Affiliation country: Italy
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Camptothecin / Introns / Colorectal Neoplasms / Antibodies, Monoclonal, Humanized / ErbB Receptors Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: En Journal: Pharmacogenomics J Journal subject: BIOLOGIA MOLECULAR / FARMACOLOGIA Year: 2014 Type: Article Affiliation country: Italy