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Clinical Research

Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients

Prostate Cancer and Prostatic Diseases volume 18, pages 144–148 (2015)Cite this article

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Abstract

Background:

Ketoconazole is a well-known CYP17-targeted systemic treatment for castration-resistant prostate cancer (CRPC). However, most of the published data has been in the pre-chemotherapy setting; its efficacy in the post-chemotherapy setting has not been as widely described. Chemotherapy-naïve patients treated with attenuated doses of ketoconazole (200–300 mg three times daily) had PSA response rate (>50% decline) of 21–62%. We hypothesized that low-dose ketoconazole would likewise possess efficacy and tolerability in the CRPC post-chemotherapy state.

Methods:

Men with CRPC and performance status 0–3, adequate organ function and who had received prior docetaxel were treated with low-dose ketoconazole (200 mg orally three times daily) and hydrocortisone (20 mg PO qAM and 10 mg PO qPM) until disease progression. Primary endpoint was PSA response rate (>50% reduction from baseline) where a rate of 25% was to be considered promising for further study (versus a null rate of <5%); 25 patients were required. Secondary endpoints included PSA response >30% from baseline, progression-free survival (PFS), duration of stable disease and evaluation of adverse events (AEs).

Results:

Thirty patients were accrued with median age of 72 years (range 55–86) and median pre-treatment PSA of 73 ng ml−1 (range 7–11,420). Twenty-nine patients were evaluable for response and toxicity. PSA response (>50% reduction) was seen in 48% of patients; PSA response (>30% reduction) was seen in 59%. Median PFS was 138 days; median duration of stable disease was 123 days. Twelve patients experienced grade 3 or 4 AEs. Of the 17 grade 3 AEs, only 3 were attributed to treatment. None of the two grade 4 AEs were considered related to treatment.

Conclusions:

In docetaxel pre-treated CRPC patients, low-dose ketoconazole and hydrocortisone is a well-tolerated, relatively inexpensive and clinically active treatment option. PSA response to low-dose ketoconazole appears historically comparable to that of abiraterone in this patient context. A prospective, randomized study of available post-chemotherapy options is warranted to assess comparative efficacy.

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Acknowledgements

This study was supported by the VA Career Development Award-2 (PI: Pan), VA Merit (PI: Pan; Grant #1I01BX001784) and the NCI Cancer Center Support Grant (PI: de Vere White). Statistical Support was provided by the Biostatistics Shared Resource through the UC Davis Comprehensive Cancer Center Support Grant, P30CA093373-06. Clinical Trials Registration: ClinicalTrials.gov Identifiers NCT00895310.

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Authors and Affiliations

  1. Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA

    E N Lo, L A Beckett, C-X Pan, D Robles & P N Lara Jr

  2. VA Northern California Health Care System, Mather, CA, USA

    C-X Pan

  3. Kaiser-Permanente Medical Center, Vallejo, CA, USA

    J M Suga

  4. Lahey Hospital and Medical Center, Burlington, MA, USA

    J M Sands

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  1. E N Lo
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Correspondence to P N Lara Jr.

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Annual Meeting of the American Society of Clinical Oncology Genitourinary Symposium, January 2014, San Francisco, CA, USA.

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Lo, E., Beckett, L., Pan, CX. et al. Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients. Prostate Cancer Prostatic Dis 18, 144–148 (2015). https://doi.org/10.1038/pcan.2015.2

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