- 作者：Russell J. Schilder ; William E. Brady ; Heather A. Lankes ; James V. Fiorica ; Mark S. Shahin ; Xun C. Zhou ; Robert S. Mannel ; Harsh B. Pathak ; Wei Hu ; R. Katherine Alpaugh ; Anil K. Sood ; Andrew K. Godwin
- 关键词：Dasatinib ; Ovarian ; Cancer ; SRC ; Inhibition
- 刊名：Gynecologic Oncology
- 出版年：2012
- 出版时间：October, 2012
- 年：2012
- 卷：127
- 期：1
- 页码：70-74
- 全文大小：205 K
Objectives
Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome.Methods
Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100 mg orally daily of dasatinib continuously until progression of disease or adverse effects prevented further treatment. Primary endpoints were progression-free survival (PFS) ¡Ý 6 months and response rate. Serial plasma samples were assayed for multiple biomarkers. Circulating free DNA was quantified as were circulating tumor and endothelial cells.
Results
Thirty-five (35) patients were enrolled in a two-stage sequential design. Of the 34 eligible and evaluable patients, 20.6 % (90 % confidence interval: 10.1 % , 35.2 % ) had a PFS ¡Ý 6 months; there were no objective responses. Grade 3-4 toxicities were gastrointestinal (mostly nausea and emesis; n = 4), pulmonary (dyspnea and/or pleural effusion; n = 4) and pain (n = 5), and infrequent instances of anemia, malaise, insomnia, rash, and central nervous system hemorrhage. Lack of clinical activity limited any correlation of biomarkers with outcome.
Conclusion
Dasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC.