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

被引：11

作者：

Loupakis, F. ^{[1
,2
]}

Antoniotti, C. ^{[1
,2
]}

Cremolini, C. ^{[1
,2
]}

Zhang, W. ^{[3
]}

Yang, D. ^{[3
]}

Wakatsuki, T. ^{[3
]}

Bohanes, P. ^{[3
]}

Schirripa, M. ^{[1
,2
]}

Salvatore, L. ^{[1
,2
]}

Masi, G. ^{[1
,2
]}

Ricci, V. ^{[4
]}

Graziano, F. ^{[5
]}

Ruzzo, A. ^{[6
]}

Benhaim, L. ^{[3
]}

Marmorino, F. ^{[1
,2
]}

Ning, Y. ^{[3
]}

El-Khoueiry, R. ^{[3
]}

Falcone, A. ^{[1
,2
]}

Lenz, H-J ^{[3
]}

机构：

[1] Azienda Osped Univ Pisana, UO Oncol Med Univ 2, I-56126 Pisa, Italy

[2] Ist Toscano Tumori, Florence, Italy

[3] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Med Oncol, Los Angeles, CA 90033 USA

[4] Ist Sci San Raffaele, Unita Oncol, Milan, Italy

[5] Hosp Pesaro, Med Oncol Unit, Pesaro, Italy

[6] Univ Urbino, Dept Biomol Sci, Sect Biochem & Mol Biol, I-61029 Urbino, Italy

来源：

PHARMACOGENOMICS JOURNAL | 2014年 / 14卷 / 04期

关键词：

cetuximab; colorectal cancer; EGFR intron 1; polymorphism; predictive biomarkers; GROWTH-FACTOR-RECEPTOR; EVERY 2ND WEEK; BIWEEKLY CETUXIMAB; 1ST-LINE TREATMENT; K-RAS; KRAS; POLYMORPHISMS; THERAPY; CHEMOTHERAPY; SURVIVAL;

D O I：

10.1038/tpj.2014.1

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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 presenting < and >= 20 CA repeats were defined as short (S) and long (L), respectively. One hundred and fifteen patients 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.

引用

页码：322 / 327

页数：6

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