A phase II trial of imatinib mesylate in patients with prostate specific antigen progression after local therapy for prostate cancer

Authors

  • Kamakshi Rao,

    1. The Dean and Betty Gallo Prostate Cancer Center at The Cancer Institute of New Jersey, New Brunswick, New Jersey
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  • Susan Goodin,

    1. Department of Medicine, University of Medicine and Dentistry Robert Wood Johnson Medical School, New Brunswick, New Jersey
    2. The Dean and Betty Gallo Prostate Cancer Center at The Cancer Institute of New Jersey, New Brunswick, New Jersey
    3. Ernest Mario School of Pharmacy, Rutgers The State University of New Jersey, Piscataway, New Jersey
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  • Michael J. Levitt,

    1. Department of Medicine, University of Medicine and Dentistry Robert Wood Johnson Medical School, New Brunswick, New Jersey
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  • Nisha Dave,

    1. The Dean and Betty Gallo Prostate Cancer Center at The Cancer Institute of New Jersey, New Brunswick, New Jersey
    2. Ernest Mario School of Pharmacy, Rutgers The State University of New Jersey, Piscataway, New Jersey
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  • Weichung J. Shih,

    1. Division of Biometrics/Statistics, The Cancer Institute of New Jersey, New Brunswick, New Jersey
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  • Yong Lin,

    1. Division of Biometrics/Statistics, The Cancer Institute of New Jersey, New Brunswick, New Jersey
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  • Terry Capanna,

    1. The Dean and Betty Gallo Prostate Cancer Center at The Cancer Institute of New Jersey, New Brunswick, New Jersey
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  • Susan Doyle-Lindrud,

    1. The Dean and Betty Gallo Prostate Cancer Center at The Cancer Institute of New Jersey, New Brunswick, New Jersey
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  • Parisa Juvidian,

    1. Department of Pathology, Robert Wood Johnson University Hospital, New Brunswick, New Jersey
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  • Robert S. DiPaola

    Corresponding author
    1. Department of Medicine, University of Medicine and Dentistry Robert Wood Johnson Medical School, New Brunswick, New Jersey
    2. The Dean and Betty Gallo Prostate Cancer Center at The Cancer Institute of New Jersey, New Brunswick, New Jersey
    • The Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08901.
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Abstract

PURPOSE

To test the hypothesis that progression of androgen sensitive prostate cancer is dependent on growth factors, such as platelet derived growth factor (PDGF), and inhibition of PDGF receptor (PDGF-R) with imatinib will induce anti-tumor activity.

PATIENTS AND METHODS

This phase II study evaluated imatinib in patients with androgen sensitive prostate cancer and prostate specific antigen (PSA) progression after local therapy. Patients received 400 mg of imatinib orally twice a day for 24 weeks (six cycles). Patients were monitored every 4 weeks for an effect on PSA and toxicity. Immunohistochemistry (IHC) for PDGF-R was performed in available tumor specimens.

RESULTS

Twenty-one patients were enrolled on this trial with a median age of 64 years. A total of 72 cycles of therapy were administered. Sixteen patients were evaluable for a response. Nine of the 16 patients demonstrated a stable PSA. Seven patients demonstrated PSA progression. Grade 3 and 4 toxicity included rash (4.1%), hematuria (1.4%), diarrhea (1.4%), and neutropenia (2.7%). Testosterone levels did not change during therapy. Four patients with available tumor demonstrated PDGF-R alpha and beta by IHC.

CONCLUSIONS

This first study evaluated the efficacy and safety of imatinib in patients with early androgen sensitive prostate cancer following local therapy. As a single agent at this dosing, imatinib had limited biochemical activity. © 2004 Wiley-Liss, Inc.

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