Abstract | BACKGROUND: METHODS: The therapeutic and endocrine effects of ketoconazole and liarozole in patients with disseminated prostatic cancer are discussed, including data from the literature and personal experience. RESULTS: Using high-dose ketoconazole, medical castration with the expected clinical response was achieved easily in previously untreated patients in all clinical series (personal data include seven patients). In patients with prostatic cancer who had relapses after castration, few objective remissions were achieved. By contrast, long-lasting subjective remissions, especially pain relief, were seen in more than half of the patients (personal data include 20 patients). Gastrointestinal intolerance, which was the main side effect, severely limits the routine use of the drug. Recently, the authors studied the effect of liarozole on adrenal steroid production in castrated patients whose disease was progressive after first-line treatment. Unlike ketoconazole therapy, adrenal androgen and cortisol levels were not modified. A Phase I-II trial was then done in 44 patients with metastatic prostatic cancer in clinical relapse. In patients with measurable disease, objective responses, including tumoral volume reduction, occurred in approximatively 30%. A prostate specific antigen reduction of 50% or more was noted in approximatively 50% of patients. Pain relief occurred in most patients. Mucocutaneous side effects were observed in most patients--dryness of the skin and onychomalacia. Raised tissue retinoic acid levels suggested a possible pathway by which this drug might exert its cytotoxic effects. CONCLUSIONS:
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Authors | C Mahler, J Verhelst, L Denis |
Journal | Cancer
(Cancer)
Vol. 71
Issue 3 Suppl
Pg. 1068-73
(Feb 01 1993)
ISSN: 0008-543X [Print] United States |
PMID | 8428329
(Publication Type: Clinical Trial, Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Review)
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Chemical References |
- Androgen Antagonists
- Glucocorticoids
- Imidazoles
- Mineralocorticoids
- Testosterone
- liarozole
- Ketoconazole
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Topics |
- Aged
- Aged, 80 and over
- Androgen Antagonists
(administration & dosage, pharmacology)
- Glucocorticoids
(metabolism)
- Humans
- Imidazoles
(administration & dosage, pharmacology)
- Ketoconazole
(administration & dosage, pharmacology)
- Male
- Middle Aged
- Mineralocorticoids
(metabolism)
- Neoplasm Recurrence, Local
(drug therapy)
- Neoplasm Staging
- Prostatic Neoplasms
(drug therapy, pathology)
- Remission Induction
- Testosterone
(metabolism)
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