Abstract
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) ≥ 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 ≥ 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.
Original language | English (US) |
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Pages (from-to) | 70-74 |
Number of pages | 5 |
Journal | Gynecologic oncology |
Volume | 127 |
Issue number | 1 |
DOIs | |
State | Published - Oct 2012 |
Keywords
- Cancer
- Dasatinib
- Inhibition
- Ovarian
- SRC
ASJC Scopus subject areas
- Oncology
- Obstetrics and Gynecology