Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: DrugBank:BIOD00113 (Zoladex)
 313 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The depot LH-RH agonist Zoladex was used to treat 38 patients with previously untreated symptomatic stage D2 prostate carcinoma. Side effects were minimal and patient acceptability excellent, although temporary tumor flare occurred in 11% of patients. Eighty-four percent experienced subjective improvement and 87% had objective evidence of initial disease stabilization or remission lasting 3 months. Serum levels of gonadotrophin and free testosterone as well as androgens of adrenal origin fell significantly with treatment. Long-term survival to date appears at least as good as that described for conventional endocrine therapy.
 ...
PMID:Zoladex treatment of symptomatic prostatic carcinoma. 297 67

A study comparing Zoladex 3.6 mg depot with diethylstilbestrol (DES) 3 mg/day was initiated in August 1985. One hundred ninety-three patients with histologically confirmed prostate cancer T3/4 or M1 have been randomized up to 31 March 1987: 95 to Zoladex, 98 to DES. No patient had received prior systemic therapy. There is no bias in the treatment groups in terms of baseline characteristics. Median follow-up is 11 months, and the response rate at 12 months from randomization (CR + PR) for Zoladex is 70 +/- 9.4% and 50 +/- 10.1% for DES. Median time to best response is 6 months for Zoladex and 12 months for DES (using the Kaplan-Meier life table method). Subjective responses are 56 +/- 10.2% for Zoladex and 44 +/- 10% for DES. Five increases in bone pain were found after the first Zoladex treatment, as well as one increased ureteric obstruction. None required treatment withdrawal. Seventeen patients on DES were withdrawn due to adverse reaction (chi 2 = 4.33, 1df, p less than 0.05). Overall survival at 31 March 1987 is 84% for the Zoladex group and 78% for the DES group. This study has shown that Zoladex is superior to DES in achieving early tumor response in advanced prostate cancer, without causing serious complications warranting withdrawal of treatment.
 ...
PMID:Interim report of a randomized trial comparing Zoladex 3.6 mg depot with diethylstilbestrol 3 mg/day in advanced prostate cancer. The West Midlands Urology Research Group. 297 73

Analogs of GnRH, given chronically in a continuous fashion, produce a paradoxic inhibition of pituitary gonadotropin secretion and, consequently, gonadal steroidogenesis. Thus, GnRH analogs are an attractive class of compounds for achieving a medical castration in the treatment of hormone-dependent neoplasms. In a group of 25 premenopausal patients with progressive advanced breast cancer, daily sc administration of 1-10 mg Leuprolide [D-Leu6-Pro9GnRH ethylamide (NEt)] induced objective tumor regression in 44% with a median duration of 9 months. All women treated for at least 10 weeks developed amenorrhea. Profound suppression of gonadotropins, estradiol, and progesterone secretion occurred in all patients on chronic therapy and persisted for the whole treatment period. These effects on tumor growth and ovarian hormone levels are similar to those observed after surgical ovariectomy. Other GnRH analogs such as Buserelin and Zoladex have been found to have similar antitumor and hormonal effects which are also comparable to those produced by surgical ovariectomy. The mode of drug administration is important. Consistent suppression of ovarian function has only been observed with sc injections of the analogs. Chronic intranasal therapy has been found to induce an incomplete suppression of ovarian function in most patients, probably as a result of the poor absorption of these compounds through this route (approximately 2%). Treatment of metastatic breast cancer with GnRH analogs has been associated with remarkable absence of significant toxicity. Despite some evidence in favor of a direct antitumor effect independent of suppression of ovarian function, the use of GnRH analogs in the therapy of advanced breast cancer should be restricted to premenopausal women.
 ...
PMID:Treatment of breast cancer with gonadotropin-releasing hormone. 308 18

Seventy patients with clinical stage C carcinoma of the prostate were treated for 3 months with the gonadotropin-releasing hormone analog, goserelin acetate (Zoladex; Zeneca Pharmaceuticals, Macclesfield, UK) plus an antiandrogen (flutamide). Based on digital rectal examination (DRE), reductions of the size of the prostate and the tumor were noted in 91.4% of patients. Ultrasound demonstrated a decrease in prostatic volume between 0% and 62.5% (median 31%). Prostate-specific antigen (PSA) levels (Hybritech) decreased substantially (mean PSA of 31.3 ng/ml before, to a mean PSA of 1.4 ng/ml after hormonal treatment). A total of 64 patients subsequently underwent radical retropubic prostatectomy. Pathologically, only 9 patients (14.1%) had organ-confined disease (stage B), 34 (53.1%) had stage C tumors, and 21 (32.8%) had positive lymph nodes (stage D1). In 5 patients with nodal metastasis and 7 patients with seminal vesicle invasion, PSA levels after pretreatment were below 0.5 ng/ml. Maximal androgen blockade for a period of 3 months in clinical stage C prostate cancer induces a notable reduction in prostate size ("downsizing"). A "downstaging" effect, as suggested by DRE, ultrasound, and PSA, was not observed. Prospective studies with this treatment regimen should concentrate on a possible benefit concerning local and distant cancer control and survival.
 ...
PMID:Hormone therapy prior to radical prostatectomy in patients with clinical stage C prostate cancer. 751 31

The patient was a 38-year-old woman who was diagnosed as having right breast cancer (T1aN1bM0, stage II) at the age of 36 when she underwent right mastectomy. Postoperative adjuvant therapy was performed using UFT and tamoxifen. After 2 years and 4 months, pulmonary metastasis was diagnosed from elevated tumor markers and chest X-P. After the relapse, treatment with goserelin acetate (Zoladex) and CPA was started. After 2 months of this treatment, the tumor in the lung had shrunk in size, and after 5 months partial remission (PR) was evaluated from improvements in chest X-P and normalization of tumor markers, This PR condition continues at present. A case report is presented of a patient with premenopausal recurrent breast cancer in whom good results were obtained by concomitant administration of Zoladex and CPA.
 ...
PMID:[Improvement of recurrent lung metastasis of breast cancer by Zoladex and cyclophosphamide]. 771 24

Two hundred consecutive patients with presumed localized prostate cancer had radical prostatectomy alone (n = 119) or were treated for an average period of 3 months with combination therapy using the antiandrogen flutamide and one luteinizing hormone-releasing hormone (LHRH) agonist (Lupron or Zoladex). The positive margins decreased from 35.3% in the group undergoing prostatectomy alone to 11.5% in the group of men who received combination therapy before radical prostatectomy. In 41 apical tumors, the incidence of positive margins decreased from 50% in the control group to 18.6% in the combination therapy group. In stage C disease, the incidence of positive tumor showed a tendency to decrease with the extended duration of endocrine treatment with a rate of 37.5% after 3 months and 16.7% after 6 months. Whether the decreased incidence of positive surgical margins will all translate into prolonged survival remains to be verified by long-term follow-up of these patients. However, the initial results obtained in the present study are very encouraging.
 ...
PMID:Hormone ablation therapy as neoadjuvant treatment to radical prostatectomy. 801 57

The main goal of hormonotherapy in management of locally advanced or metastatic prostate cancer is the control over the progression of the neoplastic disease rather than a possible benefit to the primary lesion. Nevertheless during hormonal treatment an evident decrease of prostatic volume can often be noted even though its clinical meaning has rarely been investigated. In order to evaluate a possible correlation between local modifications and prognosis, a retrospective analysis of a group of patients on hormonotherapy was performed. From March 1987 to March 1991, 98 patients with clinical stage C and D2 prostate cancer were treated. Fifty two of them were considered eligible for assessing local response because they had had neither surgery nor radiotherapy over the prostate; moreover their pre-treatment prostatic volume, as assessed by US scan, exceeded 22 ml. Out of these patients 24 were given Goserelin every 4 weeks and the remaining 28 added Flutamide at the dose of 750 mg per day. The prostatic volume was assessed quarterly and considered as response if decreased more than 35% of pretreatment value or as progression if increased over 25% of immediately previous value. In both cases the result needed to be confirmed three months later, but it was registered when first observed. After a mean follow-up of 32.4 +/- 18.7 months a local response occurred in 44 patients (84.6%) during a period ranging 3 to 18 months. Eight patients did not show a prostatic volume decrease and 4 suffered of local progression. In these latter cases the local progression coincided with distant progression.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Clinical significance of the local response to prostatic carcinoma during hormonotherapy]. 802 25

The therapeutic options for the treatment of androgen-independent prostatic cancers are rather limited; this is mainly because our understanding of the local mechanisms involved in the control of androgen-independent proliferation of the tumor is still very poor. The present experiments have been performed to verify whether luteinizing hormone-releasing hormone (LHRH) agonists may possess a direct effect on the growth of the human androgen-independent prostate cancer cells DU 145 and whether a LHRH growth regulatory system may be present in these cells. The data have shown that two potent LHRH agonists (Zoladex and Buserelin) exert a significant and dose-dependent antiproliferative action on DU 145 cells, after 4 days of treatment. The inhibitory action of Zoladex and Buserelin is completely counteracted by the simultaneous treatment of the cells with a potent LHRH antagonist, suggesting that the action of the LHRH agonists may be mediated by specific receptors. This hypothesis has been confirmed by the demonstration that low-affinity binding sites for 125I-Buserelin are present on DU 145 cell membranes, particularly when cells are cultured in serum-free conditions. By using the reverse transcription-polymerase chain reaction technique, in the presence of a pair of specific oligonucleotide primers complementary to the human LHRH complementary DNA, it has been demonstrated that a mRNA for LHRH is expressed in DU 145 cells. Taken together, these data seem to indicate that an autocrine/paracrine LHRH (or LHRH-like) loop is present in androgen-independent prostate cancer cells, and may participate in the regulation of tumor cell growth. To verify this hypothesis, DU 145 cells have been cultured in serum-free conditions, and treated with a LHRH antagonist for 4 days. The treatment resulted in a significant increase of cell proliferation, suggesting an inhibitory role for the LHRH system in the local regulation of cell growth. In conclusion, these data demonstrate that: (a) LHRH agonists exert a specific antiproliferative action on the human androgen-independent DU 145 cells; (b) an autocrine/paracrine LHRH (or LHRH-like) loop, which seems to be inhibitory on cell proliferation, is expressed in DU 145 cells.
 ...
PMID:Antiproliferative effects of luteinizing hormone-releasing hormone (LHRH) agonists on human androgen-independent prostate cancer cell line DU 145: evidence for an autocrine-inhibitory LHRH loop. 803 42

Although many investigations have shown a correlation between elevated gonadotropin levels and ovarian tumors (the gonadotropin theory), the ovarian response to a specific suppression of the gonadotropins has not been elucidated. The ovaries of (C57BL/6J x C3H/HeJ)F1-Wx/Wv mice, which contain 1% of the normal oocyte count at birth, rapidly lose the follicular apparatus and develop a 100% incidence of bilateral complex tubular adenomas from the surface germinal epithelium, which is also the origin of 90% of human ovarian carcinomas. Plasma levels of LH and FSH are known to rise fourfold during the period of tumorigenesis. We compared tumor development in Wx/Wv mice after either injecting a GnRH agonist (3.6 mg slow-release goserelin depot, Zoladex Depot) or administering a sham injection every 28 days from the age of 7 days up to 245 days. All 15 Wx/Wv mice that received sham injections developed bilateral ovarian tubular adenomas from the surface germinal epithelium. In none of the 11 mice receiving the GnRH agonist was any tumor found (p < 0.00005), and a significant suppression of the gonadotropins was demonstrated (p < 0.00005).
 ...
PMID:Gonadotropin-releasing hormone agonist suppression of ovarian tumorigenesis in mice of the Wx/Wv genotype. 854 69

Androgens stimulate the growth of prostatic carcinoma, possibly by modulating the activity of locally expressed growth factors. Recently, we have shown that an LHRH (or LHRH-like) system exerting an inhibitory action on cell proliferation is present in the human androgen-dependent prostatic tumor cell lines LNCaP. The following experiments have been performed in LNCaP cells to clarify whether LHRH might inhibit cell proliferation by interfering with the two major mitogenic factors for these cells: (a) testosterone (T), the major exogenous stimulating factor, and (b) epidermal growth factor (EGF), one of the locally produced growth factors. (a) It has been shown that an LHRH agonist (LHRH-A, Zoladex) counteracts the proliferative action of T in a dose-dependent way. To clarify whether LHRH might interfere with the activity of T in prostate tumors, LNCaP cells were treated with LHRH agonist over different time intervals, and the effects of treatment evaluated in terms of expression of androgen receptor mRNA. The data obtained indicate that LHRH-A does not affect androgen receptor expression at any time interval examined. (b) LHRH-A inhibits the mitogenic action of EGF on LNCaP cells and significantly reduces the concentration of EGF receptors in these cells. Experiments have been performed to explore whether LHRH-A might alter intracellular signaling mechanisms mediating the activity of EGF. In LNCaP cells LHRH-A blocks EGF-induced expression of the c-fos proto-oncogene but does not modify EGF-induced tyrosine phosphorylation of the EGF receptor. These data suggest that, in androgen-dependent prostate tumors, LHRH might inhibit cell proliferation by interfering with some but not all of the mechanisms mediating the mitogenic action of EGF. Possible interactions between LHRH and T-activated events still remain to be elucidated.
 ...
PMID:Growth factors in steroid-responsive prostatic tumor cells. 873 5


<< Previous 1 2 3 4 5 Next >>