Disease relevance of

• PURPOSE: We evaluated the pharmacokinetics, safety and efficacy of the implantable Viadur++ leuprolide delivery system during 12 months in patients with advanced prostate cancer [1].
• Results of this study show that LA treatment of leiomyomas results in a decrease in number of cycling cells [2].
• Two doses of Depo-Lupron, 7.5 mg, and Megace, 160 mg/day, were given to control uterine bleeding and shrink the tumor mass [3].
• It was suggested that TAP-144-SR may be a potential candidate as an agent for hormonal chemoprevention in breast cancer [4].
• Effects of TAP-144-SR, a sustained-release formulation of a potent GnRH agonist, on experimental endometriosis in the rat [5].

High impact information on

• Although no difference was found between GnRH-treated and nontreated groups with respect to most histological features examined, immunohistochemical studies showed a significant decrease in the cellular proliferation index, ER, and PR expression in the LA-treated cases compared with nontreated controls [2].
• The cellular proliferation index, ER, and PR expression decreased by 85%, 49%, and 36%, respectively, in the LA-treated group as compared with controls (P < .001) [2].
• A subset of cases from the LA-treated and nontreated groups were also analyzed with respect to bcl-2 (an inhibitor of apoptosis) expression, and no significant difference between the LA-treated and nontreated groups was observed with both groups showing a strong (> 75% of cells) cytoplasmic staining pattern [2].
• 6) When we treated the animals with TAP-144-SR (GnRH analogue) or performed an ovariectomy, which caused diminution of serum estradiol and progesterone levels, the message of HOGP was significantly decreased [6].
• OBJECTIVES: To evaluate the Viadur implant, which delivers leuprolide acetate for the palliative treatment of advanced prostate cancer [7].

Chemical compound and disease context of

• The therapeutic effects of TAP-144-SR (biodegradable microcapsules of copoly (DL-lactic/glycolic acid) copolymer containing a potent GnRH agonist, TAP-144 (D-Leu6-[des-Gly10-NH2]-GnRH ethylamide, leuprolide acetate) were studied with this rat endometriosis model [5].
• CONCLUSION: Endometriosis patients who were treated with norethindrone acetate following Lupron-Depot had significantly less breakthrough bleeding than those given norethindrone acetate alone, and the incidence was comparable to Lupron-Depot alone [8].

Biological context of

• All leiomyomas were removed by myomectomies from premenopausal woman after 2 to 6 months of LA treatment or in the follicular phase of the menstrual cycle in the untreated controls [2].
• Although ineffective when used alone, TAP-144 inhibited in a dose-dependent fashion the oestradiol-induced cell growth in oestrogen receptor-positive and oestrogen-sensitive MCF-7, ZR-75-1 and CG-5 cells [9].
• When rats were given effective doses of TAP-144 twice a day on day 9 by either route, ovulation occurred the next day (day 10) and the fetuses were aborted on day 11 [10].
• METHODS: Production of sex hormones was suppressed with daily administration of leuprolide acetate (LA), a gonadotropin-releasing hormone analogue, for 5 weeks in women who were participating in a study on pharmacologically induced menopause and physiology [11].
• The cytotoxic effect of cis-diamminedichloroplatinum II (cisplatin, CDDP) on spermatogenesis in BALB/C mice, and possible protection of the testes by leuprolide acetate (D-Leu-6 LHRH(1-9)-ethylamide, TAP-144, leuprolide), a synthetic gonadotropin-releasing hormone analogue, were examined [12].

Anatomical context of

• In TAP-144- treated mice, enhanced tumor growth was related to many solid corpora lutea in ovaries and fully developed mammary glands, but reversed growth was related to atrophied luteal components and mammary glands [13].
• Both daily injections of TAP-144 solution and a single injection of TAP-144-SR (equivalent to 0.02, 0.2 or 2 mg/kg/day as TAP-144) decreased the weight of the testes, prostates and seminal vesicles in a dose-dependent manner in a 4-week assay in male rats [14].

Associations of with other chemical compounds

• Based on the need for improved convenience of administration, a novel formulation of leuprolide acetate (Eligard; Atrix Laboratories Inc. & Sanofi Aventis) which incorporates a mixture of selected polymers and solvents to achieve sustained drug delivery after subcutaneous injection, was developed [15].
• With 4 years of clinical experience with Viadur now available, the long-term data indicate continued, uniform testosterone suppression into the castrate range and a high degree of patient satisfaction [16].

Gene context of

• Northern blot hybridization was used to determine the GnRH-R mRNA concentration several times after an injection of TAP-144-SR, a slow releasing GnRHa [17].
• These results indicate that the paradoxical effects were more extensive upon TAP-144-SR treatment, suggesting that maintaining constant serum TAP-144 levels results in more extensive desensitization of the pituitary and testes [14].
• METHODS: Adult male rats were castrated by either a single injection of gonadotropin-releasing hormone analogue (Leuplin, 1.0 mg/kg, subcutaneously) or bilateral orchiectomy [18].

Analytical, diagnostic and therapeutic context of

• Serum LH and FSH concentrations after TAP-144 administration showed similar patterns with the different routes but the peak concentration of LH after vaginal administration was higher than that after other routes [19].
• By using these antisera, a specific and sensitive radioimmunoassay for TAP-144 was established [20].
• Viadur is one aspect of a comprehensive approach to patient management, which also includes regular followup for prostate-specific antigen testing, digital rectal examination, and other tests throughout the 1-year therapy [21].
• The Viadur implants was designed to be maintenance-free, thereby allowing nurses and other health professionals to focus on other patient needs, such as followup visits and diagnostic tests [21].
• The potency of the paradoxical effects of TAP-144-SR was evaluated 4 weeks after treatment by comparing it with that of TAP-144 solution administered daily for 4 weeks [14].

References