Southwest Oncology Group study S0413: a phase II trial of lapatinib (GW572016) as first-line therapy in patients with advanced or metastatic gastric cancer

被引:104
作者
Iqbal, S. [1 ]
Goldman, B. [2 ]
Fenoglio-Preiser, C. M. [3 ]
Lenz, H. J.
Zhang, W.
Danenberg, K. D. [4 ]
Shibata, S. I. [5 ]
Blanke, C. D. [6 ]
机构
[1] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Div Med Oncol, Los Angeles, CA 90033 USA
[2] SW Oncol Grp, Ctr Stat, Seattle, WA USA
[3] Univ Cincinnati, Dept Pathol, Cincinnati, OH USA
[4] Response Genet Inc, Los Angeles, CA USA
[5] City Hope Natl Med Ctr, Dept Med Oncol, Duarte, CA 91010 USA
[6] Univ British Columbia, Dept Med Oncol, British Columbia Canc Agcy, Vancouver, BC V5Z 1M9, Canada
关键词
EGFR; gastric cancer; HER2; lapatinib; EPIDERMAL-GROWTH-FACTOR; FACTOR-RECEPTOR; EGF-RECEPTOR; GASTROESOPHAGEAL JUNCTION; KINASE INHIBITOR; EXPRESSION; COMBINATION; CARCINOMA; CETUXIMAB; C-ERBB-2;
D O I
10.1093/annonc/mdr021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Lapatinib (GW572016) is a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2/ErbB2), which are reported as overexpressed in 15%-45% of gastric cancers, making them potential targets. Patients and methods: The primary objective of this study was to assess response rate. Secondary objectives included overall survival (OS), toxicity, and the relationship of EGFR, ErbB2, and markers of angiogenesis with clinical outcome. Lapatinib was administered to chemonaive metastatic gastric cancer patients at a dose of 1500 mg orally daily for 28 days. Results: The study enrolled 47 patients from February 2005 until May 2006. Four patients (9%) had a confirmed partial response (PR), 1 (2%) had an unconfirmed PR, and 10 (23%) had stable disease. Median (95% confidence interval) time to treatment failure was 1.9 (1.6-3.1) months and OS was 4.8 (3.2-7.4) months. Significant adverse events: one grade 4 cardiac ischemia/infarction, one grade 4 fatigue, and one grade 4 emesis. One treatment-related death was due to central nervous system ischemia. An exploratory analysis of markers revealed gene expression of HER2, interleukin (IL)-8 and genomic polymorphisms IL-8, and vascular endothelial growth factor correlated with OS. Conclusions: Lapatinib is well tolerated, with modest single-agent activity in advanced/metastatic gastric cancer patients. Potential molecular correlatives were identified which warrant further validation.
引用
收藏
页码:2610 / 2615
页数:6
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