Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis: A Hoosier Oncology Group trial

Daniela Matei, Robert E. Emerson, Jeanne Schilder, Nancy Menning, Lee Ann Baldridge, Cynthia S. Johnson, Tim Breen, John McClean, Doyle Stephens, Charles Whalen, Gregory Sutton

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57 Scopus citations

Abstract

BACKGROUND. Ovarian tumors frequently express c-Kit and/or platelet-derived growth factor receptors (PDGFRs). Imatinib mesylate blocks the growth of ovarian cancer cells in vitro and may enhance the activity of chemotherapy. This study was conducted to determine the activity of imatinib in combination with docetaxel in patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). METHODS. Eligible patients had recurrent, platinum-resistant, or refractory EOC that expressed PDGFRα or c-kit, as determined by immunohistochemistry. Imatinib mesylate at a dose of 600 mg orally once daily was administered continu-ously with docetaxel at a dose of 30 mg/m2 given intravenously once weekly in Weeks 1 through 4 of every 6-week cycle. The primary endpoint was objective response rate (ORR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS. Thirty-four patients were screened for PDGFRα and c-kit expression to enroll 23 patients between December 2003 and October 2005. Four patients had c-kit-positive/PDGFR-negative tumors, 11 patients had PDGFR-positive/c-kit-negative tumors, and 8 patients had c-kit-positive/PDGFR-positive tumors. The median patient age was 56 years (range, 33-76 years). Patients had received a median of 3 prior treatments. The ORR was 21.7% and included 1 complete and 4 partial responses. An additional 3 patients had stable disease for more than 4 months. Expression of PDGFR, c-kit, phosphatase and tensin homolog (PTEN), and phosphorylated protein kinase B (Akt) did not predict response to therapy. The most common adverse events encountered were fatigue (83%), nausea (74%), diarrhea (61%), anorexia (52%), and edema (65%), and the majority of those events were graded as grade 1 or 2. CONCLUSIONS. The combination imatinib and docetaxel was tolerated in patients with heavily pretreated EOC that expressed c-kit or PDGFRα. Few patients had sustained responses or stable disease.

Original languageEnglish (US)
Pages (from-to)723-732
Number of pages10
JournalCancer
Volume113
Issue number4
DOIs
StatePublished - Aug 15 2008

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Keywords

  • c-kit
  • Docetoxel
  • Imatinib
  • Ovarian cancer
  • Phosphorylated kinase B
  • Platelet-derived growth factor receptors
  • Tumor microenvironment

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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