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Ketoconazole for mCRPC


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Contemporary experience with ketoconazole in patients with metastatic castration-resistant prostate cancer: Clinical factors associated with PSA response and disease progression - Abstract

Fri, 08 July 2011

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland.


Adrenal/intratumoral androgen biosynthesis contributes to ligand-dependent androgen receptor activation in metastatic castration-resistant prostate cancer (mCRCP). Compounds targeting CYP-17 hydroxylase and lyase, as ketoconazole and abiraterone, block adrenal/intratumoral androgen biosynthesis, and are used as sequential endocrine approaches in mCRCP. We aimed to describe contemporary experience and association of clinical factors with Prostate specific antigen (PSA) response and disease progression, in mCRPC progressing on GnRH-agonist, antiandrogen, antiandrogen withdrawal, and treated with ketoconazole.

Data were retrospectively analyzed in all mCRPC patients treated with ketoconazole. Patients continued GnRH-agonist, and treated with ketoconazole 200-400mg 3× a day until dose-limiting toxicity or disease progression. A multivariate cox regression model was used to identify clinical factors associated with PSA response and disease progression.

From 1999 to 2010, 114 mCRPC patients were treated with ketoconazole. With a median follow-up time of 31 months (range 5-129), 25 patients (22%) had grade 3/4 toxicity, most commonly fatigue, abdominal discomfort, nausea, and dizziness. Sixty-one patients (54%) had >50% PSA decline. Median time to progression was 8 months (range 1-129). Factors associated with PSA response and disease progression were response to prior antiandrogen (>6 vs. < 6 months), pre-treatment PSADT (>3 vs. < 3 months) and extent of disease (limited-axial skeleton and/or nodal vs. extensive-appendicular skeleton and/or visceral).

Ketoconazole is effective and safe in mCRPC. Prior response to antiandrogen, pre-treatment PSADT, and disease extent are associated with PSA response and disease progression, and further supports a therapeutic role in suppressing adrenal androgens in mCRPC.

Written by:

Keizman D, Huang P, Carducci MA, Eisenberger MA.

Reference: Prostate. 2011 Jun 17. Epub ahead of print.

doi: 10.1002/pros.21447

PubMed Abstract

PMID: 21688281 Forum: Secondary hormone therapy Title: Ketoconazole for mCRPC

This extract can be found on http://PubMed.com, and is in the public domain.

On PubMed.com there will be a link to the full paper (often $30, sometimes free).

Any highlighting (except the title) is not by the author, but by Jim Marshall.

Jim is not a doctor.

This page was found on the Advanced Prostate Cancer Community for Australian men at http://advancedprost...lia.ipbhost.com.

The link is hard to remember.

An easier way to find it is to go to JimJimJimJim.com and click on Prostate.

That's the word Jim four times, no spaces, followed by .com.

If you need other help - to perhaps find someone to talk to or a local support group:

Click on the Contact Jim button at http://JimJimJimJim.com.

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