The Journal of Urology
Volume 183, Issue 6 , Pages 2219-2226 , June 2010

A Phase I Clinical Study of High Dose Ketoconazole Plus Weekly Docetaxel for Metastatic Castration Resistant Prostate Cancer

  • William D. Figg

      Affiliations

    • Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • Corresponding Author InformationCorrespondence and requests for reprints: Medical Oncology Branch, Building 10/Room 5A01, 9000 Rockville Pike, Bethesda, Maryland 20892 (telephone: 301-402-3623; FAX: 301-402-8606)
    • ,
  • Sukyung Woo

      Affiliations

    • Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • Wenhui Zhu

      Affiliations

    • Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • Xiaohong Chen

      Affiliations

    • Clinical Pharmacology Program, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • A. Seun Ajiboye

      Affiliations

    • Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • Seth M. Steinberg

      Affiliations

    • Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • Douglas K. Price

      Affiliations

    • Molecular Pharmacology Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • John J. Wright

      Affiliations

    • Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • Howard L. Parnes

      Affiliations

    • Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • Philip M. Arlen

      Affiliations

    • Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • James L. Gulley

      Affiliations

    • Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
    • ,
  • William L. Dahut

      Affiliations

    • Medical Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland

Received 8 October 2009

  • Image Result

    PFS (A) and OS (B) for patients with or without prior docetaxel therapy

    PFS (A) and OS (B) for patients with or without prior docetaxel therapy

  • Image Result

    Pharmacokinetic interaction between docetaxel and ketoconazole (KETO). Effects of docetaxel on exposure to ketoconazole (A) in patients receiving 1,200, 800 or 600 mg ketoconazole daily. Mean plasma c

    Pharmacokinetic interaction between docetaxel and ketoconazole (KETO). Effects of docetaxel on exposure to ketoconazole (A) in patients receiving 1,200, 800 or 600 mg ketoconazole daily. Mean plasma concentration of docetaxel vs time profiles (B) at doses of 16 to 43 mg/m2 in absence (open circles) and presence (closed circles) of 600 mg ketoconazole daily. Fold changes in docetaxel AUC by ketoconazole co-administration (C) are shown, as is correlation between ketoconazole AUC and fold changes in docetaxel CL (D). Solid line is generated from linear regression and broken lines represent 95% CI.

  • Image Result
    Effects of ABCB1 polymorphism on pharmacokinetics of docetaxel alone (A to C) and in presence of 600 mg ketoconazole daily (D to F).

    Effects of ABCB1 polymorphism on pharmacokinetics of docetaxel alone (A to C) and in presence of 600 mg ketoconazole daily (D to F).

 Study received institutional review board approval.

 Supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. The results and discussions presented herein do not represent the views of these federal agencies.

 For another article on a related topic see page 2409.

PII: S0022-5347(10)00261-2

doi: 10.1016/j.juro.2010.02.020

The Journal of Urology
Volume 183, Issue 6 , Pages 2219-2226 , June 2010

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