کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5882541 1149547 2015 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original StudyMET Abnormalities in Patients With Genitourinary Malignancies and Outcomes With c-MET Inhibitors
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی بیهوشی و پزشکی درد
پیش نمایش صفحه اول مقاله
Original StudyMET Abnormalities in Patients With Genitourinary Malignancies and Outcomes With c-MET Inhibitors
چکیده انگلیسی

BackgroundThe purpose of this study was to determine the prevalence of MET amplification and mutation among GU malignancies and its association with clinical factors and responses to c-MET inhibitors.Patients and MethodsPatients with GU malignancies referred to our Phase I Clinical Trials Program were evaluated for MET mutation and amplification and outcomes using protocols with c-MET inhibitors.ResultsMET amplification was found in 7 of 97 (7.2%) patients (4/27 renal [all clear cell], 1/18 urothelial, and 2/12 adrenocortical carcinoma), with MET mutation/variant in 3 of 54 (5.6%) (2/20 renal cell carcinoma [RCC] [1 clear cell and 1 papillary] and 1/16 prostate cancer). No demographic characteristics were associated with specific MET abnormalities, but patients who tested positive for mutation or amplification had more metastatic sites (median, 4 vs. 3 for wild type MET). Median overall survival after phase I consultation was 6.1 and 11.5 months for patients with and without a MET alteration, respectively (hazard ratio, 2.8; 95% confidence interval, 1.1 to 6.9; P = .034). Twenty-nine (25%) patients were treated according to a c-MET inhibitor protocol. Six (21%) had a partial response (prostate and RCC) and 10 (34%) had stable disease as best response. Median time to tumor progression was 2.3 months (range, 0.4-19.7) for all treated patients with no responses in patients with a MET abnormality or single-agent c-MET inhibitor treatment.ConclusionMET genetic abnormalities occur in diverse GU malignancies and are associated with a worse prognosis in a phase I setting. Efficacy of c-MET inhibitors was more pronounced in patients without MET abnormalities and when combined with other targets/drugs.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Genitourinary Cancer - Volume 13, Issue 1, February 2015, Pages e19-e26
نویسندگان
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