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Phase I/II trial of neoadjuvant sunitinib administered with weekly paclitaxel/carboplatin in patients with locally advanced triple-negative breast cancer

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Abstract

The purpose of the study is to evaluate the feasibility and efficacy of adding sunitinib to paclitaxel/carboplatin in the neoadjuvant therapy of patients with triple-negative breast cancer (TNBC). Patients had histologically proven, previously untreated, triple-negative adenocarcinoma, with disease limited to the breast and axilla (clinical T1–T3, N0–N2, M0; T1N1M0 excluded). Following determination of the maximum tolerated doses in the phase I portion, patients in the phase II study received paclitaxel 70 mg/m2 IV days 1, 8, and 15; carboplatin AUC 5.0 IV day 1; sunitinib 25 mg orally daily; treatment was administered for six 28-day cycles followed by definitive surgery. Sunitinib was resumed postoperatively to complete a 52-week course. Pathologic complete response (pCR) rate was the primary endpoint. Fifty-four patients enrolled; 41 received treatment in the phase II study. Sixteen patients (39 %) were able to complete six cycles of neoadjuvant therapy; 18 additional patients had surgery after completing 2–5 cycles of treatment. The pCR rate in these 34 evaluable patients was 35 %. The toxicity of the regimen was considerable, with myelosuppression resulting in numerous dose reductions and/or omissions of paclitaxel and carboplatin. Eleven patients (27 %) discontinued sunitinib during neoadjuvant therapy, and six patients (14 %) completed 52 weeks of single-agent sunitinib. In the neoadjuvant treatment of patients with TNBC, the combination of paclitaxel, carboplatin, and sunitinib was difficult to administer, and produced a pCR rate comparable to other less toxic regimens. This combination is not recommended for further evaluation. At present, sunitinib has no defined role in the treatment of breast cancer.

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Acknowledgments

Supported in part by a grant from Pfizer.

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Authors and Affiliations

  1. Sarah Cannon Research Institute, Nashville, TN, USA

    Denise A. Yardley, Dianna L. Shipley, Nancy W. Peacock, Mythili Shastry, Rajiv Midha & John D. Hainsworth

  2. Tennessee Oncology, PLLC, 250 25th Avenue North, Suite 100, Nashville, TN, 37203, USA

    Denise A. Yardley, Dianna L. Shipley, Nancy W. Peacock & John D. Hainsworth

  3. Center for Cancer and Blood Disorders, Bethesda, MD, USA

    Victor M. Priego

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  1. Denise A. Yardley
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Correspondence to Denise A. Yardley.

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Appendix

Appendix

Participating SCRI consortium sites

Tennessee Oncology, PLLC

Nashville, TN

National Capital Clinical Research Consortium

Bethesda, MD

Florida Cancer Specialists

Ft. Myers, FL

Baptist Hospital East

Louisville, KY

Center for Cancer and Blood Disorders

Bethesda, MD

Family Cancer Center Foundation, Inc.

Memphis, TN

Cancer Centers of Southwest Oklahoma

Lawton, OK

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Yardley, D.A., Shipley, D.L., Peacock, N.W. et al. Phase I/II trial of neoadjuvant sunitinib administered with weekly paclitaxel/carboplatin in patients with locally advanced triple-negative breast cancer. Breast Cancer Res Treat 152, 557–567 (2015). https://doi.org/10.1007/s10549-015-3482-4

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