Phase II evaluation of dasatinib in the treatment of recurrent or persistent epithelial ovarian or primary peritoneal carcinoma: A gynecologic oncology group study

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

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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 languageEnglish (US)
Pages (from-to)70-74
Number of pages5
JournalGynecologic oncology
Volume127
Issue number1
DOIs
StatePublished - Oct 2012

Keywords

  • Cancer
  • Dasatinib
  • Inhibition
  • Ovarian
  • SRC

ASJC Scopus subject areas

  • Oncology
  • Obstetrics and Gynecology

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