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

References 

  1. Smith BD, Smith GL, Hurria A, et al. Future of cancer incidence in the United States: burdens upon an aging, changing nation. J Clin Oncol. 2009;27:2758
  2. Damber JE, Aus G. Prostate cancer. Lancet. 2008;371:1710
  3. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004;351:1502
  4. Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004;351:1513
  5. Petrylak DP. Future directions in the treatment of androgen-independent prostate cancer. Urology. 2005;65:8
  6. Blagosklonny MV, Dixon SC, Figg WD. Efficacy of microtubule-active drugs followed by ketoconazole in human metastatic prostate cancer cell lines. J Urol. 2000;163:1022
  7. Sella A, Kilbourn R, Amato R, et al. Phase II study of ketoconazole combined with weekly doxorubicin in patients with androgen-independent prostate cancer. J Clin Oncol. 1994;12:683
  8. Engels FK, Ten Tije AJ, Baker SD, et al. Effect of cytochrome P450 3A4 inhibition on the pharmacokinetics of docetaxel. Clin Pharmacol Ther. 2004;75:448
  9. Van Veldhuizen PJ, Reed G, Aggarwal A, et al. Docetaxel and ketoconazole in advanced hormone-refractory prostate carcinoma: a phase I and pharmacokinetic study. Cancer. 2003;98:1855
  10. Halabi S, Small EJ, Kantoff PW, et al. Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. J Clin Oncol. 2003;21:1232
  11. Huang YC, Colaizzi JL, Bierman RH, et al. Pharmacokinetics and dose proportionality of ketoconazole in normal volunteers. Antimicrob Agents Chemother. 1986;30:206
  12. Daneshmend TK, Warnock DW, Turner A, et al. Pharmacokinetics of ketoconazole in normal subjects. J Antimicrob Chemother. 1981;8:299
  13. Figg WD, Liu Y, Arlen P, et al. A randomized, phase II trial of ketoconazole plus alendronate versus ketoconazole alone in patients with androgen independent prostate cancer and bone metastases. J Urol. 2005;173:790
  14. Marcelin-Jimenez G, Hernandez J, Angeles AP, et al. Bioequivalence evaluation of two brands of ketoconazole tablets (Onofin-K and Nizoral) in a healthy female Mexican population. Biopharm Drug Dispos. 2004;25:203
  15. Trump DL, Havlin KH, Messing EM, et al. High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects. J Clin Oncol. 1989;7:1093
  16. Johnson DE, Babaian RJ, von Eschenbach AC, et al. Ketoconazole therapy for hormonally refractive metastatic prostate cancer. Urology. 1988;31:132
  17. Vanuytsel L, Ang KK, Vantongelen K, et al. Ketoconazole therapy for advanced prostatic cancer: feasibility and treatment results. J Urol. 1987;137:905
  18. Oh WK. Secondary hormonal therapies in the treatment of prostate cancer. Urology. 2002;60:87
  19. Eklund J, Kozloff M, Vlamakis J, et al. Phase II study of mitoxantrone and ketoconazole for hormone-refractory prostate cancer. Cancer. 2006;106:2459
  20. Wire MB, Ballow CH, Borland J, et al. Fosamprenavir plus ritonavir increases plasma ketoconazole and ritonavir exposure, while amprenavir exposure remains unchanged. Antimicrob Agents Chemother. 2007;51:2982
  21. Small EJ, Halabi S, Dawson NA, et al. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol. 2004;22:1025
  22. Berthold DR, Pond GR, Soban F, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008;26:242
  23. Sissung TM, Baum CE, Deeken J, et al. ABCB1 genetic variation influences the toxicity and clinical outcome of patients with androgen-independent prostate cancer treated with docetaxel. Clin Cancer Res. 2008;14:4543
  24. Lepper ER, Baker SD, Permenter M, et al. Effect of common CYP3A4 and CYP3A5 variants on the pharmacokinetics of the cytochrome P450 3A phenotyping probe midazolam in cancer patients. Clin Cancer Res. 2005;11:7398
  25. Hamada A, Sissung T, Price DK, et al. Effect of SLCO1B3 haplotype on testosterone transport and clinical outcome in caucasian patients with androgen-independent prostatic cancer. Clin Cancer Res. 2008;14:3312

 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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