leuprolide and fosfestrol

We investigated the influence of flutamide on plasma adrenal androgens in advanced prostate cancer patients treated with dietylstilbestrol diphosphate (DES-DP) followed by luteinizing hormone-releasing hormone agonist (LH-RH agonist). Nine patients were enrolled in this study and they were divided into the following two treatment groups; group A: LHRH agonist mono-therapy (n = 4) and group B: LHRH agonist with flutamide (n = 5). For prevention of flare up, all patients were treated with DES-DP.. Two-week DES-DP administration led to reduction of plasma adrenal androgen levels. These levels were kept lower for 16 weeks in group B in contrast with group A in which the levels returned to the pretreatment levels. Basal ACTH levels in group B were significantly lower than those in group A.. From our observations, we found that flutamide reduced adrenal androgen levels in prostate cancer patients treated with LH-RH agonist. ACTH suppression might be related to this phenomenon.

Topics: Adrenocorticotropic Hormone; Aged; Androgens; Depression, Chemical; Diethylstilbestrol; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms

To determine whether administration of estrogen or gestagen prior to luteinizing hormone-releasing hormone (LH-RH) agonist prevents disease flare in prostate cancer patients, we pretreated the patients with either diethylstilbestrol diphosphate (DES-P) 300 mg daily (N = 17) or chlormadinone acetate (CMA) 100 mg daily (N = 16) or none (N = 16) for two weeks before the initial injection of leuprolide acetate (L). Blood samples for prostatic specific antigen (PSA), testosterone (T), and luteinizing hormone were collected before CMA and DES-P administration, before and at 2, 7, 14, 28, 56, and 84 days after the first administration of leuprolide. The treatment with DES-P and CMA prior to LH-RH agonist induced an early decline of PSA. The mean PSA level showed no significant secondary rise in those patients with pretreatment after L administration. In the patients pretreated with DES-P or CMA, the mean serum T level never exceeded the pretreatment baseline after L administration. On the other hand, in the patients without DES-P or CMA, both serum T and PSA levels increased after the first administration of L. These results clearly demonstrate that pretreatment with DES-P 300 mg daily or CMA 100 mg daily for 2 weeks is quite effective to prevent disease flare after the first administration of L in patients with prostatic cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Autacoids; Chlormadinone Acetate; Diethylstilbestrol; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Neoplasm Recurrence, Local; Premedication; Progesterone Congeners; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Serum levels of LH, FSH and testosterone (T) were measured by radioimmunoassays in 36 patients with advanced prostate cancer before and during androgen ablation therapies. Both leuprolide acetate (LH-RH agonist: LHRH-A) and diethylstilbestrol diphosphate (DES-DP) administration decreased serum LH significantly to an undetectable level (LHRH-A: P < 0.01, DES-DP: P < 0.05). LHRH-A and DES-DP diminished serum FSH to 20% of the pre-treatment level (P < 0.005) and to an undetectable level (P < 0.001), respectively. LHRH-A and DES-DP decreased serum T to the castration level and an undetectable level, respectively (P < 0.001). Serum levels of the same 3 hormones before and after DES-DP administration were measured in 8 patients who received DES-DP after LHRH-A treatment or castration because of relapse of the disease. DES-DP lowered serum FSH further than LHRH-A to an undetectable level (P < 0.005) and diminished T further than previous treatments to an undetectable level (P < 0.05 vs. LHRH-A, P < 0.01 vs. castration). These results suggest that 1) DES-DP is able to reduce T production from extra-testicular site(s), and achieve the minimal serum T level, and 2) this DES-DP action appears to be one of the mechanisms of the effectiveness of the estrogen on refractory prostate cancer after castration or LHRH-A. In addition, basal (independent of LH-RH) FSH secretion in elderly men is about 20% of total FSH secretion and DES-DP inhibits the basal FSH secretion at the level of the pituitary.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Diethylstilbestrol; Follicle Stimulating Hormone; Humans; Leuprolide; Male; Orchiectomy; Prostatic Neoplasms; Receptors, LHRH; Retrospective Studies; Testosterone

The objective of this study was to elucidate the mechanism underlying the further suppression of serum testosterone (T) by diethylstilbestrol diphosphate (DES-DP) in patients with prostate cancer refractory to hormonal treatment. These patients received an LHRH agonist with or without a non-steroidal androgen-receptor blocker or a gestagen before DES-DP. We measured serum levels of total and free T, dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione, cortisol, aldosterone before and during intravenous administration of high doses of DES-DP (500 or 1000 mg/day). DES-DP administration suppressed the serum levels of FSH (p=0.04) and total T (p=0.02), and eliminated free T (p=0.04) and E2 (p=0.04) from serum, while reducing serum DHEA-S to approximately two-thirds of the pretreatment level (p=0.03). In contrast, serum levels of SHBG (p=0.02) and cortisol (p=0.02) were markedly increased after DES-DP administration. The latter had no significant effect on serum levels of LH, DHT, ACTH, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, DHEA, androstenedione, or aldosterone. The results suggest that the potent suppression of circulating total T by DES-DP is caused, in part, by the inhibitory effect of DES-DP on serum DHEA-S level. In most patients, high-dose DES-DP treatment completely suppressed the serum level of free T, while possibly elevating serum SHBG and decreasing serum total T. The mechanisms that maintain the serum level of serum DHT during DES-DP treatment require further elucidation.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents; Chlormadinone Acetate; Dehydroepiandrosterone Sulfate; Diethylstilbestrol; Drug Resistance, Neoplasm; Estradiol; Follicle Stimulating Hormone; Goserelin; Hormones; Humans; Hydrocortisone; Leuprolide; Male; Middle Aged; Progesterone Congeners; Prostatic Neoplasms; Sex Hormone-Binding Globulin; Testosterone