Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

589 patients from 10 countries are recruited into a multicentre randomised trial comparing Zoladex with a combination of Zoladex-Depot + flutamide. Zoladex was administered as a depot injection every 28 days and flutamide was given as 3 x 250 mg tablets daily. Patients with histologically confirmed locally advanced (T3/T4) or metastatic (M1) carcinoma were included. Patients with previous hormonal manipulation and/or chemotherapy were excluded. 65% of patients had metastatic disease. Both treatment groups were balanced (T-category, histology, metastases, performance status). An analysis of subjective and objective response, time to response and time to progression has shown no statistically significant difference. A survival analysis after a median follow-up of 24 months has shown no statistically significant difference between the two treatment groups (p = 0.47).
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PMID:[Randomized study comparing zoladex versus zoladex plus flutamide in treatment of advanced cancer of the prostate]. 146 45

Serum testosterone and prostate-specific antigen (PSA) levels were measured in 3 patients with Stage D2 prostate cancer before and after discontinuation of the long-acting LHRH agonist, goserelin acetate (Zoladex). The patients had received goserelin acetate for ten, sixteen, and thirty months prior to discontinuing the drug because of progressive metastatic disease. In all 3 patients, PSA and testosterone levels increased after goserelin acetate was discontinued. In 2 patients the testosterone level reached normal levels. A bilateral orchiectomy was performed one hundred sixty, one hundred, and seven days, respectively, after the drug was discontinued. In all 3 cases PSA and testosterone levels were reduced following castration, although PSA levels again began to increase within two weeks of orchiectomy in 2 of the 3 patients. These findings suggest that suppression of testosterone by LHRH agonists is not permanent and if tumor progression occurs, maintaining hormone suppression may still be beneficial.
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PMID:Response to orchiectomy following Zoladex therapy for metastatic prostate carcinoma. 170 66

Between November 1983 and February 1986, 358 patients with previously untreated metastatic prostatic carcinoma entered a multicentre, randomised trial in the United Kingdom and the Republic of Ireland, in which the LHRH analogue Zoladex (ICI Pharmaceuticals PLC), administered subcutaneously every 28 days, was compared with orchiectomy. Both treatments were equally effective in lowering serum testosterone concentrations to within the surgically castrate range and this was accompanied by equivalent subjective and objective response rates and times to treatment failure. At a median follow-up of 2 years there was no difference in overall survival, confirming that Zoladex is an effective medical alternative to orchiectomy in patients with metastatic disease.
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PMID:Comparison of LHRH analogue (Zoladex) with orchiectomy in patients with metastatic prostatic carcinoma. 153 12

Continuous administration of gonadotrophin-releasing hormone (GnRH-)analogues leads to a receptor-down regulation of pituitary GnRH-receptors and subsequently inhibits ovarian hormone production. Since October, 1984, 118 evaluable pre- and perimenopausal patients (median age 42, range 25-55 years) with metastatic breast cancer were entered into an open phase II multicenter trial to evaluate efficacy of this new treatment modality. Patients were treated with the GnRH-analogue Goserelin (3.6 mg depot s.c. every 4 weeks) as first line therapy and followed up until progression. Mean serum gonadotrophins LH and FSH were significantly suppressed by Goserelin. Within 2-3 weeks, mean serum E2 values decreased to values seen in castrated women (less than 30 pg/ml). Overall objective response with complete and partial remissions (CR + PR) was achieved in 44.9% of patients with a median time to progression (mTTP) of 59 weeks, (range 20-163 weeks), no change (NC) in 28.0% with a mTPP of 27 weeks (range 16-101 weeks), and progression (P) in 27.1%. Responses were seen in ER-positive as well as ER-negative tumors, and in patients with different sites of metastases (locoregional, bone, visceral, multiple). The value of different prognostic factors in relation to response rates, time to progression and time to death (overall survival) is discussed. Median overall survival (time from beginning of palliative Goserelin treatment to death) was 148 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The depot GnRH analogue goserelin in the treatment of premenopausal patients with metastatic breast cancer--a 5-year experience and further endocrine therapies. Cooperative German Zoladex Study Group. 182 49

A prospective randomized trial was conducted to compare the effects of the nonsteroidal antiandrogen flutamide (250 mg. 3 times daily) plus the luteinizing hormone-releasing hormone analogue goserelin acetate (Zoladex) (3.6 mg. subcutaneous depot injection every 28 days) with goserelin acetate alone in advanced prostatic carcinoma. A total of 571 eligible patients, of whom 57% had distant metastases, showed no difference in subjective or objective response rates, interval to progression, treatment failure or survival after a median followup of 2 years. In the combination group more patients had an early decrease in elevated levels of tumor markers and the small number of patients with an increase in signs and symptoms within the first 4 weeks showed a significant decrease. However, increased gastrointestinal and hepatic toxicity in the combination group resulted in 44 patients being withdrawn from the trial. These results indicate that the combination of goserelin acetate with flutamide provides no long-term clinical benefit in patients with advanced prostatic carcinoma compared to goserelin acetate alone.
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PMID:A multicenter randomized trial comparing the luteinizing hormone-releasing hormone analogue goserelin acetate alone and with flutamide in the treatment of advanced prostate cancer. The International Prostate Cancer Study Group. 183 64

The levels of prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP), both measured by radioimmunoassay, and two cancer indices given by the ratio of serum alpha-1 acid glycoprotein to prealbumin (AGP:Palb) and alpha-1 acid glycoprotein to alpha-2 HS globulin (AGP:HS) were evaluated as markers to assess the response of prostatic cancer to treatment with Zoladex, an LH-RH agonist. A rise in PSA and PAP occurred in 8/65 patients (12%) during the initial induction phase. In metastatic disease prior to treatment none of these indices was significantly different between patients who attained a sustained response and those whose response was nil or only transient. Responders and non-responders could, however, be distinguished by the levels of various analytes after treatment. At 6 months the median PSA in those who responded was 2.5 ng/ml compared with 51.5 ng/ml in the non-responders. At 12 months the figures were 3.0 and 155 ng/ml respectively. The corresponding median PAP levels were 1.4 and 19 ng/ml at 6 months and 1.3 and 18 ng/ml at 12 months. The AGP:Palb ratio was also significantly different in these two groups at 6 and 12 months. PSA appears to be the most sensitive indicator of the response to treatment. The likelihood of obtaining a prolonged clinical response can be assessed within 6 months of the start of treatment.
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PMID:Biochemical monitoring of carcinoma of prostate treated with an LH-RH analogue (Zoladex). 243 85

One hundred and thirty-nine patients with advanced prostate cancer were entered into a randomised trial to test the efficacy and tolerance of goserelin 3.6 mg depot (Zoladex) versus stilboestrol 3 mg/day. As well as the usual clinical and radiological assessments of extent of disease, we used an immunoradiometric assay of prostate specific antigen (PSA) (Hybritech Europe) and normal laboratory enzymatic assays of acid phosphatase (AP) and alkaline phosphatase (ALKP) for biochemical assessment. The upper limit of normal for PSA was taken as 10 micrograms/l. The range of PSA was wide and differed significantly from that of AP and to a lesser extent ALKP in metastatic cases. PSA outperformed both AP and ALKP in both the local and advanced groups in terms of sensitivity. There was no correlation, however, between histological grade and level of PSA, AP or ALKP (the latter in cases with bone disease). In patients with metastatic disease diagnosed by bone scan, nine patients had one abnormal site/one "hot spot", and all of these had a PSA greater than twice the normal upper limit. Early death due to prostate cancer was noted in four patients with levels of PSA greater than 2500 micrograms/l. PSA is more sensitive than either enzymatic AP or ALKP in both locally advanced and metastatic prostate cancer and is useful in identifying those advanced cases who have single lesions on bone scan. In this series PSA gave an overall sensitivity of 89%, compared with 63% for AP and 64% for ALKP in patients with metastatic disease.
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PMID:The role of prostate specific antigen in the baseline assessment of patients undergoing hormone therapy for advanced prostate cancer. 244 97

One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.
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PMID:Goserelin, a depot gonadotrophin-releasing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. German Zoladex Trial Group. 252 63

The clinical and endocrine response to a depot preparation of the LH-RH analogue ICI 118630 (Zoladex) was assessed in 55 untreated patients with advanced prostatic cancer. Whereas gonadal androgen suppression was achieved in all patients, subjective and objective clinical response occurred in only 69%, indicated by a relief of bone pain, a decrease in the size of the primary tumour and lymph node metastases and improvement in bone scan appearances. A third of these patients, however, subsequently showed progression of their disease. Serious side effects were not encountered in this study. The depot formulation is a simple, safe and convenient method of administering Zoladex and offers an alternative treatment for metastatic prostatic cancer.
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PMID:The treatment of metastatic prostatic cancer with the slow release LH-RH analogue Zoladex ICI 118630. 295 5

Twenty-two patients with metastatic cancer of the prostate were treated with ZoladexR, an LHRH analogue. In all cases plasma testosterone levels decreased to post-surgical castration values. This inhibitory effect of Zoladex on testicular steroid production had a favourable influence on the course of the malignancy, since 75 p. 100 of objective responses were obtained after 3 months of treatment. The functional symptoms were distinctly improved, and the drug was well tolerated, notably by the cardiovascular system. This immediate effectiveness seemed to last for several months, one-half of the patients still being in remission after 3 to 15 months. The beneficial effects of LHRH agonists, similar to those of pulpectomy or oestrogen therapy, are limited by the susceptibility of the tumour to hormones. In view of their effectiveness and good tolerance, LHRH agonists are useful in the management of advanced prostatic cancer, either as initial therapy or to replace a poorly tolerated oestrogen therapy. Further studies are needed to clarify their indications and the possible value of their association with anti-androgens or antimitotic drugs.
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PMID:[Value of a LHRH agonist (Zoladex) in hormonotherapy of advanced cancers of the prostate. Apropos of 22 patients]. 295 58


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