High-dose ketoconazole treatment in advanced prostatic cancer

1988 ◽  
Vol 20 (4) ◽  
pp. 383-393 ◽  
Author(s):  
S. Scultéty ◽  
J. Oszlánczy ◽  
I. Faredin ◽  
I. Tóth
Keyword(s):  
Prostatic Cancer ◽  
High Dose ◽  
Advanced Prostatic Cancer

High-dose ketoconazole in advanced hormone-refractory prostate cancer: endocrinologic and clinical effects.

1989 ◽  
Vol 7 (8) ◽  
pp. 1093-1098 ◽  
Author(s):  
D L Trump ◽  
K H Havlin ◽  
E M Messing ◽  
K B Cummings ◽  
P H Lange ◽  
...  
Keyword(s):  
Prostatic Cancer ◽  
Dehydroepiandrosterone Sulfate ◽  
Plasma Testosterone ◽  
High Dose ◽  
Clinical Effects ◽  
Advanced Prostatic Cancer ◽  
Androgen Ablation ◽  
Days Of Therapy ◽  
Hormone Refractory ◽  
Moderate Nausea

High-dose ketoconazole (400 mg orally three times a day) and physiologic replacement doses of glucocorticoids (hydrocortisone, 20 mg 8 AM, 10 mg 4 PM, and 8 PM) were administered to 38 patients with advanced prostatic cancer, refractory to at least initial testicular androgen deprivation. Thirty patients were completely evaluable; six were withdrawn due to possible ketoconazole-related toxicity and were considered drug failures. Two patients were unevaluable due to intercurrent therapy or inability to maintain follow-up. Ketoconazole was generally well tolerated. Mild or moderate nausea and vomiting occurred in 37% of patients, but required dose modification or discontinuation in only three patients; no hepatic damage was seen. Five of 36 patients (14%) responded to ketoconazole as determined by palpable or radiographic tumor mass reduction of 50% or greater and normalization of acid phosphatase or bone scan. Fifty percent of patients entered were stable at 90 days. Plasma androstenedione and dehydroepiandrosterone sulfate (DHEAS) were reduced markedly in almost all patients. Plasma testosterone (T) levels were low and remained unchanged, while gonadotropins were persistently elevated. Mean plasma ketoconazole content was 6.6 micrograms/mL after 28 days of therapy. While ketoconazole with hydrocortisone does suppress plasma androgens in advanced prostatic cancer patients, this infrequently causes regression of cancer that has progressed despite adequate testicular androgen ablation.

Endocrine effects of high-dose ketoconazole therapy in advanced prostatic cancer

1985 ◽  
Vol 110 (2) ◽  
pp. 276-283 ◽  
Author(s):  
W. Heyns ◽  
A. Drochmans ◽  
E. van der Schueren ◽  
G. Verhoeven
Keyword(s):  
Serum Concentration ◽  
Prostatic Cancer ◽  
Inverse Correlation ◽  
Serum Testosterone ◽  
Feedback System ◽  
Sex Hormone Binding Globulin ◽  
High Dose ◽  
Endocrine Effects ◽  
Advanced Prostatic Cancer ◽  
The Mean

Abstract. The endocrine effects of ketoconazole (400 mg orally every 8 h) were studied in 9 previously untreated patients with advanced prostatic cancer. Five of these patients were followed for 12 months. A rapid fall in the serum concentration of testosterone was noted in all patients studied. Minimal values were observed on day 4 of treatment but thereafter serum testosterone increased slowly. The effect of the drug on unbound testosterone was relatively more important, since sex hormone binding globulin increased markedly during treatment. An increase in progesterone and LH was observed in all patients. This suggests that ketoconazole limits the conversion of C21-precursors into androgens. This block is compensated in part by activation of the hypothalamo-hypophyseal feedback system. Urinary 17-ketosteroids were decreased but 17-hydroxysteroids were unaffected by the treatment. In 5 patients followed monthly over a period of 12 months the mean testosterone concentration ranged from 69 ng/100 ml in one patient to 428 ng/100 ml in another. An excellent inverse correlation could be demonstrated between the mean serum concentration of testosterone and the mean concentration of ketoconazole. The change of serum dehydroepiandrosterone sulphate also correlated inversely with the mean ketoconazole level. Increased concentrations of oestradiol were noted in 2 patients with slight gynaecomastia. It is concluded that long-term suppression of androgen production can be realized by high-dose ketoconazole treatment and that the degree of suppression is proportional to the serum levels of the drug.

Androgen priming and cytotoxic chemotherapy in advanced prostatic cancer

1982 ◽  
Vol 8 (3) ◽  
Author(s):  
A.J. Suarez ◽  
D.L. Lamm ◽  
H.M. Radwin ◽  
M. Sarosdy ◽  
G. Clark ◽  
...  
Keyword(s):  
Prostatic Cancer ◽  
Cytotoxic Chemotherapy ◽  
Advanced Prostatic Cancer

scholarly journals Cyclophosphamide versus cyclophosphamide, methotrexate, and 5-fluorouracil in advanced prostatic cancer: A randomized trial

Cancer ◽  
1981 ◽  
Vol 47 (8) ◽  
pp. 1949-1953 ◽  
Author(s):  
Hyman B. Muss ◽  
Virginia Howard ◽  
Frederick Richards Ii ◽  
Douglas R. White ◽  
Don V. Jackson ◽  
...  
Keyword(s):  
Randomized Trial ◽  
Prostatic Cancer ◽  
Advanced Prostatic Cancer
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