Treatment of Prostatic Carcinoma with D-Trp-6-LH-RH: Plasma Hormone Levels After Daily Subcutaneous Injections and Periodic Administration of Delayed-Release Preparations

Roger, M; Duchier, J; Lahlou, N; Nahoul, K

doi:10.1016/s0022-5347(17)45783-1

Cited by 3 publications

(4 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have demonstrated that the microcapsules are much more efficacious than multiple daily injections [7,32,33]. The efficacy of D-Trp-6-LHRH microcapsules in the treatment of advanced prostatic carcinoma was demonstrated in animal experiments and in clinical trials [31,34,35]. However, a limitation to the use of LHRH agonists alone is the transient increase in serum testosterone, resulting from augmented secretion of lutein-…”

Section: Discussionmentioning

confidence: 99%

“…Since 1983, we have been developing sustained delivery systems for peptides. These systems are based on microcapsules or microgranules of DL-lactide-co-glycolide, which are biodegradable and compatible with living tissues [33,34]. Our pharmaco-kinetic study of the release pattern of SB-75 from microcapsules demonstrated that during the therapeutically important continuous phase, the liberation of only a small amount of the peptide is required to maintain a complete suppression of the pituitary-gonadal axis in rats [41].…”

Section: Serum Testosterone Levels In Rats Injected With the Lh-rh Anmentioning

confidence: 93%

See 1 more Smart Citation

Blockade of the LH response induced by the agonist D‐Trp‐6‐LHRH in rats by a highly potent LH‐RH antagonist SB‐75

et al. 1992

View full text Add to dashboard Cite

During treatment of prostate cancer patients with luteinizing hormone-releasing hormone agonist, a transient LH and sex steroid release, which precedes the secretion blockade, may result in a flare-up of the disease, whereas the antagonists induce an immediate suppression. The administration of the modern, superactive LHRH antagonist SB-75 before or together with the agonist D-Trp-6-LHRH should prevent the "flare-up" phenomena. In order to demonstrate that the LHRH antagonist can prevent the initial stimulation of gonadotropins in response to LHRH agonists, groups of 5-7 male rats were injected s.c. with the antagonist SB-75 in doses in 100, 500, and 1,000 micrograms/rat 1 hour prior to or 1, 2, and 3 days before administration of D-Trp-6-LHRH agonist (50 micrograms/rat). Supraphysiological doses of the agonist were used in order to obtain prolonged stimulation of LH release, which was necessary to study the duration and the extent of LH release inhibition. Blood samples were taken before and 2, 6, 24, 48, and 72 hours after D-Trp-6-LHRH stimulation for measurement of LH levels. The administration of SB-75 in doses of 500 and 1,000 micrograms/rat 3 days prior to administration of the agonist significantly lowered LH response (P less than 0.01), as compared to animals injected with D-Trp-6-LHRH alone. The D-Trp-6-LHRH-stimulated LH secretion was markedly more suppressed by all 3 doses of the antagonist in rats pretreated with SB-75 2 days prior to the stimulation with the agonist. An even greater reduction in LH response could be observed in rats injected with SB-75 1 day prior to the agonist, the magnitude of LH response being decreased by 75% with 500 micrograms/rat SB-75 and by 90% with 1 mg/rat SB-75. The LH response was virtually abolished when the antagonist, SB-75 was given in doses of 500 or 1,000 micrograms/rat 1 hour prior to the D-Trp-6-LHRH injection. Under these conditions, the agonist-induced LH and testosterone secretion was completely suppressed during the whole period of the experiment. The antagonist to agonist dose ratio of 2 to 1 produced a 90% decrease in the LH response to D-Trp-6-LHRH at 2 hours and 75% at 5 hours after agonist administration. The effects of LHRH decapeptide itself (500 micrograms/rat) on LH secretion could be totally suppressed by an injection of 50 micrograms/rat of SB-75 1 hour beforehand.(ABSTRACT TRUNCATED AT 400 WORDS)

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Serum Testosterone Levels In Rats Injected With the Lh-rh Anmentioning

confidence: 93%

Blockade of the LH response induced by the agonist D‐Trp‐6‐LHRH in rats by a highly potent LH‐RH antagonist SB‐75

et al. 1992

View full text Add to dashboard Cite

show abstract

“…The results of Roger et a1 [ 181 and Parmar et al [ 191 in men with prostate cancer attest to the high clinical efficacy of once a month administration of microcapsules of suppressing testosterone secretion. The accumulated results [1][2][3][4][5][6][7]18,19] reinforce the view that long-term therapy with agonists of LH-RH is a viable alternative to surgical castration or therapy with estrogens in men with metastatic prostate cancer.…”

Section: Discussionmentioning

confidence: 79%

Persistent blockade of the pituitary‐gonadal axis in patients with prostatic carcinoma during chronic administration of D‐Trp‐6‐LH‐RH

et al. 1986

View full text Add to dashboard Cite

Forty patients with stage D2 prostatic carcinoma were treated for up to 30 months with D-Trp-6-LH-RH. The analog was given s.c. once daily at a dose of 1 mg/day for the first 7 days. Subsequently, the dose was reduced to 100 micrograms/day. In follow-up studies, 30 men continued this therapy for up to 24 months. Blood samples were taken before the injection of the analog and 1, 2, 4, and 6 hours later. Serum LH, FSH, and testosterone levels were measured by RIA every month for 2 years. The initial administration of 1 mg D-Trp-6-LH-RH caused a marked elevation of LH and FSH, which lasted more than 24 hours. However, 1 month later and throughout the therapy, the basal values of LH and FSH were below the normal range and no increase in serum gonadotropins levels was obtained after administration of the analog. Initial plasma testosterone was within normal limits, but during treatment with D-Trp-6-LH-RH it fell to castration levels, and no increases were seen during the 6 hours following the injection of the analog. These results show that chronic administration of D-Trp-6-LH-RH, at the doses used, blocks the pituitary-gonadal axis and that the escape phenomenon from the effects of the LH-RH agonists-induced blockade does not occur under our conditions in contrast to observations of Kerle et al with the I.C.I. Analog 118630 (8). The accumulated results reinforce the view that long-term therapy with agonists of LH-RH is the preferred alternative to surgical castration or therapy with estrogens in men with metastatic prostate cancer.

show abstract

“…Roger and coworkers 51 provided evidence for the efficacy of periodic administration of Decapeptyl microcapsules for suppressing testicular secretion in patients with prostate cancer. Each patient received an intramuscular injection equivalent to 3 mg Decapeptyl in microcapsules designed to deliver, in a controlled fashion, a daily dose of 100 µg D-Trp 6 LHRH for 30 days.…”

Section: Prostate Cancermentioning

confidence: 99%

Use of Luteinizing Hormone - Releasing Hormone Analogs in the Treatment of Hormone-Dependent Tumors

Schally¹,

Comaru‐Schally²

1987

Semin Reprod Med

View full text Add to dashboard Cite

Treatment of Prostatic Carcinoma with D-Trp-6-LH-RH: Plasma Hormone Levels After Daily Subcutaneous Injections and Periodic Administration of Delayed-Release Preparations

Cited by 3 publications

References 23 publications

Blockade of the LH response induced by the agonist D‐Trp‐6‐LHRH in rats by a highly potent LH‐RH antagonist SB‐75

Blockade of the LH response induced by the agonist D‐Trp‐6‐LHRH in rats by a highly potent LH‐RH antagonist SB‐75

Persistent blockade of the pituitary‐gonadal axis in patients with prostatic carcinoma during chronic administration of D‐Trp‐6‐LH‐RH

Use of Luteinizing Hormone - Releasing Hormone Analogs in the Treatment of Hormone-Dependent Tumors

Contact Info

Product

Resources

About