Among new highly potent antagonistic analogs of
luteinizing hormone-releasing hormone (
LH-RH), containing neutral hydrophilic D-ureidoalkyl
amino acids such as D-
Cit and D-Hci at position 6 and free of edematogenic and
anaphylactoid reactions, Ac-D-Nal(2)1, D-Ph(4Cl)2, D-Pal(3)3, D-Cit6, D-Ala10 (
LH-RH) (
SB-75;
Cetrorelix) was shown to be one of the most powerful. In this trial, we evaluated the response to 500 micrograms
SB-75 given every 12 hr subcutaneously (sc) for 4 weeks in 11 patients with
benign prostatic hyperplasia (BPH), and 6 weeks in 6
prostatic cancer patients (2 stage C, 4 stage D2). In patients with BPH presenting with
prostatism and urinary outflow obstruction, there was a noticeable clinical improvement after the first week of
SB-75 administration. This improvement continued during the course of treatment. Before
therapy with
SB-75, the serum levels of
prostate-specific antigen (PSA) (6.73 +/- 1.46 ng/ml),
acid phosphatases, total (12.67 +/- 1.15 U/l), and prostatic (2.27 +/- 0.34 U/l), were mildly elevated, but declined to normal values at 4 weeks: (2.13 +/- 0.59 ng/ml; P < 0.01), (7.68 +/- 0.89 U/l; P < 0.01), and (1.39 +/- 0.18 U/l; P < 0.01), respectively. Mean prostatic volume assessed by ultrasonography showed a significant decrease in all patients from 67.84 +/- 8.86 to 37.92 +/- 8.52 cm3; P < 0.01, which represents a reduction of 44%. In patients with
prostate cancer, after the first week of
therapy with
SB-75, we observed a significant decrease in bone
pain, relief in urinary outflow obstruction, and reversal of the signs of
prostatism. Subjective improvement continued during the following weeks of treatment, so that the patients no longer needed
analgesics. PSA,
acid, and alkaline
phosphatases gradually fell, achieving nearly normal values at 6 weeks. Initial serum
testosterone levels in BPH and
prostatic cancer patients were within normal limits, but during treatment with the antagonistic analog
SB-75, fell to
castration values. A major fall in free
testosterone levels was observed after the first dose; the maximal inhibition was seen after 6-12 hr, with a simultaneous decrease in levels of both
gonadotropins. Our results show that antagonist
SB-75 can be safely administered for prolonged periods of time. The rapid shrinkage of the prostate and concomitant improvement in obstructive symptoms of
prostatism obtained with antagonistic analog
SB-75 in patients with BPH may decrease the morbidity of prostatic surgery and offer a therapeutic alternative in men who are considered poor surgical risks.(ABSTRACT TRUNCATED AT 400 WORDS)