Impact of ABCG2 polymorphisms on the clinical outcome and toxicity of gefitinib in non-small-cell lung cancer patients

被引：48

作者：

Lemos, Clara ^{[1
]}

Giovannetti, Elisa ^{[1
,2
]}

Zucali, Paolo A. ^{[3
]}

Assaraf, Yehuda G. ^{[4
]}

Scheffer, George L. ^{[5
]}

van der Straaten, Tahar ^{[6
]}

D'Incecco, Armida ^{[7
]}

Falcone, Alfredo ^{[7
]}

Guchelaar, Henk-Jan ^{[6
]}

Danesi, Romano ^{[2
]}

Santoro, Armando ^{[3
]}

Giaccone, Giuseppe ^{[8
]}

Tibaldi, Carmelo ^{[7
]}

Peters, Godefridus J. ^{[1
]}

机构：

[1] Vrije Univ Amsterdam Med Ctr, Dept Med Oncol, NL-1081 HV Amsterdam, Netherlands

[2] Univ Pisa, Dept Internal Med, I-56100 Pisa, Italy

[3] Ist Clin Humanitas, Dept Med Oncol & Hematol, Milan, Italy

[4] Technion Israel Inst Technol, Fred Wyszkowski Canc Res Lab, Dept Biol, IL-32000 Haifa, Israel

[5] Vrije Univ Amsterdam Med Ctr, Dept Pathol, NL-1081 HV Amsterdam, Netherlands

[6] Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, NL-2333 ZA Leiden, Netherlands

[7] Azienda USL 6 Livorno, Dept Oncol, I-57100 Livorno, Italy

[8] NCI, Med Oncol Branch, Bethesda, MD 20892 USA

来源：

PHARMACOGENOMICS | 2011年 / 12卷 / 02期

关键词：

ABCG2; gefitinib; lung cancer; pharmacogenetics; toxicity; SINGLE NUCLEOTIDE POLYMORPHISMS; TYROSINE KINASE INHIBITORS; MULTIDRUG TRANSPORTER ABCG2; DRUG-RESISTANCE; PROTEIN; EXPRESSION; BCRP; PHARMACOKINETICS; GENE; LOCALIZATION;

D O I：

10.2217/PGS.10.172

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aims: The current study investigates whether or not functional polymorphisms in the ATP-binding cassette transporter gene ABCG2 might affect gefitinib activity and/or toxicity in non-small-cell lung cancer (NSCLC) patients. Materials & methods: Towards this end, ABCG2 polymorphisms and expression were assessed in DNA and tumors from 94 NSCLC patients treated with gefitinib, whereas their associations with toxicity/response and time-to-progression/overall survival were evaluated using Pearson-chi(2) and log-rank-test, respectively. Results: Patients carrying an ABCG2-15622T/T genotype or harboring at least one IT copy in the ABCG2 (1143C/T, -15622C/T) haplotype developed significantly more grade 2/3 diarrhea (p < 0.01). No associations were found between polymorphisms and outcome. Consistently, ABCG2 protein levels in tumors were not significantly different between patients harboring different ABCG2 variants. Conclusion: The ABCG2 -15622C/T polymorphism and ABCG2 (1143C/T, -15622C/T) haplotype resulted in a gefitinib-dependent, moderate-to-severe diarrhea suggesting that these pharmacogenetic markers should be considered to optimize NSCLC treatment.

引用

页码：159 / 170

页数：12

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