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2750036 
Journal Article 
Pharmacokinetics, endocrine and antitumor effects of leuprolide depot (TAP-144-SR) in advanced prostatic cancer: dose response evaluation 
Mazzei, T; Mini, E; Eandi, M; Reali, EF; Periti, P; Et al 
1989 
Yes 
Drugs Under Experimental and Clinical Research
ISSN: 0378-6501 
IPA/90/904162 
Clin 
REF 36 
373-387 
English 
IPA COPYRIGHT: ASHP Therapy with a sustained action leuprolide formulation (TAP-144-SR; I) in 22 patients with advanced prostatic cancer and one patient with benign prostatic hypertrophy is reported; the patients received a subcutaneous injection at doses of 3.75, 7.5, 15 or 30 mg. Drug levels were measured over a 5 wk period; patients then received the drug every 4 wk. Serum levels of I showed a rapid increase immediately after injection, reaching a peak proportional to dose within 3 h (range of mean values were 13.1-54.5 ng/ml). Subsequently, mean drug levels declined to a plateau proportional to the dose (0.49-1.99 ng/ml at 5 wk). A significant dose dependent increase in the area under the serum concentration-time curve from 0 to 35 days from 541.7 to 1653.9 ng/mlh was also noted. With all doses there was an initial rise in serum luteinizing hormone and follicle stimulating hormone, followed by a rise in testosterone and dihydrotestosterone, then sharp decrease within 3 wk. Follicle stimulating hormone inhibition was achieved in all 20 evaluable patients and was maintained in 17 of them over 5 wk. Fifteen subjects had marked suppression of luteinizing levels. In 13 of them, this condition continued for the entire observation time. Castration levels of serum testosterone and dihydrotestosterone, however, were maintained in all patients for up to 5 wk. Two of the 21 evaluable patients had a complete response, 15 a partial response and 3 stable disease. No significant differences were observed in relation to dose. It is concluded that doses of I as low as 3.75 mg provide clinical improvement with adequate gonadotropin suppression for the management of advanced prostatic cancer.