Phase II pilot trial of imatinib mesylate with weekly docetaxel in metastatic breast cancer

Author:

Barton J. H.1,Liggett W.1,Mainwaring M.1,Hainsworth J. D.1,Simons L.1,Spigel D. R.1,Burris III H. A.1,Yardley D. A.1

Affiliation:

1. Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN

Abstract

10716 Background: Overexpression of platelet derived growth factor receptor (PDGFR) has been associated with breast cancer tumor progression and may serve as a potential target for therapy. Inhibition of PDGFR signaling in tumor stroma represents a novel strategy that has demonstrated enhanced chemotherapy antitumor effects, decreased tumor interstitial fluid pressure as well as increased tumor transcapillary transport. Imatinib mesylate (G) is a potent PDGFR tyrosine kinase antagonist. This phase II pilot study evaluates the feasibility, toxicity, and efficacy of imatinib administered with docetaxel as a strategy to enhance docetaxel’s chemotherapeutic effects in metastatic breast cancer (MBC). Methods: Eligibility requirements: 0–1 prior regimens for MBC, > 6 months from prior adjuvant taxanes, RECIST measurable disease, ECOG PS 0–2, adequate organ function, < G2 neuropathy. Treatment: docetaxel 30 mg/m2 IV weekly 3 of 4 weeks. Imatinib mesylate 600 mg po QD. Pts were evaluated for response every 8 weeks; treatment continued until progression or toxicity. Results: 7 pts have been enrolled to date. Median age is 61, all with ECOG PS 0. 5 pts received prior adjuvant therapy; 2 pts received prior taxanes. 43% received prior hormonal therapy. Only 1 pt was ER+/PR+. Hematologic toxicity was mild, consisting only of G3/4 anemia in 2 pts and G3 thrombocytopenia in 1. No febrile neutropenia was noted. Nonhematologic toxicity was characterized primarily by G3 GI toxicity: 4 pts diarrhea, 3 N, V, 1 anorexia, 1 abdominal pain. This was attributed to imatinib in all but 1 pt, in whom both drugs were implicated. 2 pts were removed from treatment and 3 pts required dose reductions, all due to GI toxicity consisting of N, V, and diarrhea. 3 pts experienced dose interruptions and 2 pts exhibited disease progression. Conclusion: These early preliminary results demonstrate imatinib mesylate, in combination with weekly docetaxel as a strategy to inhibit breast cancer PDGFR signaling, is feasible. GI toxicity with this combination was prominent and warrants dose modifications. Updated toxicity and efficacy data will be presented. [Table: see text]

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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