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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
Article first published online: 10 JUL 2008
Copyright © 2008 American Cancer Society
Volume 113, Issue 4, pages 723–732, 15 August 2008
How to Cite
Matei, D., Emerson, R. E., Schilder, J., Menning, N., Baldridge, L. A., Johnson, C. S., Breen, T., McClean, J., Stephens, D., Whalen, C. and Sutton, G. (2008), Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis. Cancer, 113: 723–732. doi: 10.1002/cncr.23605
See commentary on pages 665–7, this issue.
- Issue published online: 1 AUG 2008
- Article first published online: 10 JUL 2008
- Manuscript Accepted: 30 JAN 2008
- Manuscript Revised: 7 JAN 2008
- Manuscript Received: 15 OCT 2007
- ovarian cancer;
- platelet-derived growth factor receptors;
- tumor microenvironment;
- phosphorylated kinase B
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).
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 continuously 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).
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 4months. 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.
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. Cancer 2008. © 2008 American Cancer Society.