| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 3946899 | Gynecologic Oncology | 2012 | 5 Pages |
ObjectivesPreclinical 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.MethodsEligible 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.ResultsThirty-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.ConclusionDasatinib has minimal activity as a single-agent in patients with recurrent EOC/PPC.
► No objective responses with 7 of 34 patients had PFS ≥ 6 months. ► The agent was well tolerated with the major toxicities being grade 3 nausea/emesis, pain and pulmonary. ► No detectable relationships between clinical outcome and biomarkers.
