Ketoconazole - low = high. Going low->high sometimes helps

[JimmyToowong]

Response to low-dose ketoconazole and subsequent dose escalation to high-dose ketoconazole in patients with androgen-independent prostate cancer. [Cancer. 2006]

Lank Center for Genitourinary Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115, USA.

Abstract

BACKGROUND: High-dose ketoconazole (HDK) in combination with steroids has been recognized as an effective secondary hormonal therapy in androgen-independent prostate cancer (AIPC). However, HDK causes more severe adverse events than low-dose ketoconazole (LDK). To the authors' knowledge, relatively little is known regarding the efficacy of LDK in AIPC. The efficacy of LDK and of subsequent dose escalation from LDK to HDK was evaluated as secondary hormonal therapy in patients with AIPC.

METHODS: In a single institution, patients with AIPC treated with LDK (at a dose of 200 mg orally 3 times daily) as secondary hormonal therapy with or without concomitant steroids were retrospectively identified. In addition, patients were identified who received dose escalation to HDK (400 mg orally 3 times daily) after experiencing a rising prostate-specific antigen (PSA) level.

RESULTS: Thirty-nine of 138 eligible patients (28.3%, 95% confidence interval [95% CI], 20.9-36.6%) treated with LDK experienced PSA declines > or =50%. The median time to disease progression or dose escalation on LDK was 3.2 months (range, 0.1(+)-61 months). Dose escalation to HDK was subsequently performed in 55 patients (39.9%), 7 of whom (12.7%) demonstrated a subsequent PSA decline > or =50%. A longer duration of primary androgen deprivation therapy and total duration of all previous hormonal therapies was associated with a longer time to progression with LDK (P < .05). The most common reversible adverse effect of LDK was NCI Common Toxicity Criteria Grade 1 or 2 fatigue (12.3%).

CONCLUSIONS: LDK is associated with a PSA response rate comparable to HDK as secondary hormonal therapy in patients with AIPC, but with less toxicity. Although uncommon, additional durable responses occurred in some patients after dose escalation.

References

Excerpted from Response to low-dose ketoconazole and subsequent d... [Cancer. 2006] - PubMed result

PMID: 16862573 Forum: Secondary hormone therapy Title: Ketoconazole - low = high. Going low->high sometimes helps

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