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)

From April 1984 to May 1986, 129 patients with prostate cancer entered a prospective trial with a new LH-RH agonist, Zoladex. Mean age was 72 years (range of 45-94 years) and, in most cases, patients had metastatic disease, not previously treated by chemotherapy or hormone therapy. Patients received a monthly injection of 3.6 mg. Serum testosterone was lowered into the range of castrate levels after 4 weeks of treatment. In 105 evaluable patients at 3 months, a 65% partial response (PR) rate was observed, with 11% stable and 24% progressive disease. Median time to progression was 37 weeks. Analysis of objective criteria revealed 30% PR for prostate volume and 51% CR-PR for prostatic acid phosphatases. Seventeen percent of lytic metastases had recalcified. One hundred twenty-nine patients were evaluable for toxicity. Endocrinological side effects were common: decrease in libido, 92%; impotence, 86%; hot flushes, 48%; and breast swelling or tenderness, 9%. Nonendocrinologic side effects were rare. The treatment is generally well accepted by patients owing to the convenient depot formulation and to the minor side effects.
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PMID:Zoladex as primary therapy in advanced prostatic cancer. A French cooperative trial. 297 63

Eighty patients with prostatic cancer have been treated with an LH-RH analogue (Zoladex). Ten had no metastasis, and hormone therapy was used as an induction treatment before curative radiotherapy. The others had metastatic disease and, in some cases, had already received some form of endocrine therapy. Patients received a monthly injection of Zoladex (3.6 mg). No progressive disease was noted among patients with nonmetastatic tumors; of the patients with metastases, those who were previously untreated had a higher response rate (14.8% complete response) and longer progression-free and overall survival. Toxicity was mild in spite of two cases of disease flare.
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PMID:Clinical study of an LH-RH agonist (ICI 118.630, Zoladex) in the treatment of prostatic cancer. 297 65

The trial drug was ICI 118.630 (Zoladex). Inclusion criteria were histologically confirmed advanced prostate cancer (T greater than 2 or N+ or M+), life expectancy greater than 3 months, and no previous radiotherapy, orchiectomy, or chemotherapy. Treatment started in November 1984; 30 patients were recruited. The period of treatment ranged from 6 to 144 weeks (median of 59.5 weeks). One patient died after 6 weeks of rapidly progressive renal failure. Data were updated to the end of August 1987. The mean age was 67.9 years (53-83 years). Subjective response was evaluated by a mean symptoms score (using daytime micturition, nocturia, dysuria, hesitancy, and flow) and a score of three different items: patients' activity, bone pain, and use of analgesics. Only 7.1% of the patients showed a permanent positive response. Four different objective responses (complete, partial, stable disease, and progression) were possible after evaluating the T category, tumor dimensions, metastases, and prostatic acid phosphatase. Testosterone (T) and plasmatic LH levels rose after administration: T dropped below the castration level (1 ng/ml) within a few days and remained constantly low. The rate of progressive disease was 27.6%; disease control was possible in 72.4% of the patients (PR or SD).
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PMID:LH-RH analogue treatment for advanced prostate cancer. 297 66

The first adjuvant breast cancer trial in the Southwest Oncology Group (SWOG) was initiated in 1974. The trial eventually demonstrated that combination chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, and prednisone was superior to single-agent chemotherapy with melphalan in premenopausal and postmenopausal patients. Subsequently, SWOG has performed a series of adjuvant chemotherapy trials either alone or in collaboration with other cooperative groups. Over the past 5 years, SWOG has accrued more than 8000 patients to different clinical trials in primary and advanced breast cancer as well as to a series of ancillary biologic studies primarily evaluating new prognostic factors, such as hormone receptor status and flow cytometry. Current questions being addressed by SWOG breast cancer adjuvant trials include the value of doxorubicin in lymph node-negative patients, of chemoendocrine therapy in lymph node-positive premenopausal and post-menopausal patients, and of high dose chemotherapy with autologous bone marrow transplantation in high risk lymph node-positive patients. Trials in patients with metastatic disease are evaluating medical castration with the luteinizing hormone-releasing hormone agonist Zoladex (Zeneca Pharmaceuticals, Wilmington, DE), high dose chemotherapy and bone marrow transplantation, and newer agents such as paclitaxel (Taxol, Bristol-Myers Squibb, Walingford, CT). Future adjuvant trials will compare optimal sequential use of single-agent chemotherapy versus more traditional combination chemotherapy and address questions of dose intensity and the value of the addition of Taxol in the adjuvant setting. A trial using the synthetic retinoid 4-hydroxyphenylretinamide is also in the planning stage.
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PMID:Current trials and future directions of the Southwest Oncology Group Breast Cancer Committee. 803 49

As a first effort to introduce quality-of-life assessment in prostatic cancer clinical trials, the European Organization for Research and Treatment of Cancer Genitourinary Group, in cooperation with European Organization for Research and Treatment Quality of Life Group, initiated protocol 30853, coordinated by Louis Denis. This protocol compared the efficacy of treatment with orchiectomy alone to that with Zoladex (Zeneca Pharmaceuticals, Alderley Macclesfield, Cheshire, UK) plus flutamide in previously untreated patients with metastatic cancer. The use of patient-administered quality-of-life questionnaires was optional, and of 327 patients, only 22% had pretreatment assessments. This trial revealed many clinician's considerable reluctance to perform quality of life research, partly because of feasibility problems and partly because of doctors' doubts about the value of such efforts. Psychologic distress, fatigue, issues of social and family life, and pain were found to be the most important concerns on a subjective basis, and this finding was confirmed by objective parameters. There was a discrepancy between doctors' evaluations and patients' opinions about subjective morbidity, namely sexual status and pain. Quality of life assessment should become a mandatory part of clinical trials in prostate cancer.
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PMID:Quality of life in prostatic cancer patients. 825 94

Eighty-two patients with advanced prostatic carcinoma were treated with a long-acting luteinizing hormone releasing hormone (LHRH) agonist (Zoladex depot, Zeneca Pharmaceuticals, England). The outcome of the treatment was monitored on the basis of the following prognostic factors: local stage, number of bone metastases, histological differentiation grade and prostate-specific acid phosphatase (PAP), alkaline phosphatase (AF) and testosterone levels. The patients were followed-up until disease progression or until death. The mean weight of the prostate decreased from 48.1 g to 17.4 g (P < 0.00001) during the first year of treatment. Statistically there was a significant difference in regard to appearance of progression between different clinical stages (P < 0.00001). The prognosis was poorest in patients with more than 10 metastases at the primary stage. If the PAP level was initially higher (over 20 micrograms/L), the prognosis was very poor. Statistically there was a significant difference between the high PAP level and the slightly elevated or normal PAP (P < 0.02 and P < 0.005, respectively). Alkaline phosphatase (AF) appeared to be a good prognostic factor. The prognosis was particularly poor, if the AF level exceeded 1000 U/L (P < 0.00001 and P < 0.05, compared with normal AP and slightly elevated AP level, respectively). Surprisingly, a high pre-treatment testosterone level worsened the prognosis during the LHRH agonist treatment (P < 0.01, compared to patients with normal testosterone level). This is a new finding and controversial to the findings reported before.
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PMID:Prognostic factors of advanced prostatic carcinoma. 829 78

Systemic adjuvant therapy is recommended immediately following surgical removal of the primary tumour in the majority of patients with early breast cancer, to prevent the recurrence of distant metastases. Significant progress has been made in the development and evaluation of endocrine therapies for systemic adjuvant therapy. In pre- and perimenopausal women, ovarian ablation has proven to be a valuable treatment option, though not always desirable for young patients. Thus, reversible medical ovarian suppression with a luteinizing hormone releasing hormone agonist, such as goserelin (Zoladex), may provide an attractive alternative for such patients. International trials have indicated that goserelin provides an important addition to the choice of adjuvant therapies now available to pre- and perimenopausal patients. For postmenopausal patients, it is hoped that the ATAC (Arimidex, tamoxifen, alone or in combination) trial will reveal whether or not the benefits of anastrozole (Arimidex) observed in advanced disease, where it has proven to be well tolerated and at least as effective as tamoxifen in recent trials, will translate to the early setting to provide further management options for these patients. On the horizon is yet another exciting endocrine agent, ICI 182,780 (Fulvestrant), which has also been shown to be as effective as anastrozole in advanced disease. In terms of the future, these agents are likely to provide additional valuable treatment choices for early breast cancer across the patient spectrum.
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PMID:A vision for the future? 1190 Feb 11

The use of adjuvant endocrine therapy in the treatment of hormone receptor-positive, early breast cancer has become important in both pre- and postmenopausal women. Tamoxifen has been the principal adjuvant hormonal therapy in pre- and postmenopausal women with hormone receptor-positive breast cancer for nearly 20 years. Recent data in premenopausal women suggest benefit from ovarian ablation with or without tamoxifen. Early results from the 'Arimidex', Tamoxifen, Alone or in Combination (ATAC) trial have demonstrated that the third-generation, selective aromatase inhibitor (AI) anastrozole ('Arimidex') is a suitable alternative adjuvant therapy for postmenopausal women with hormone receptor-positive disease. After recurrence or relapse on adjuvant endocrine therapy, responses to the sequential use of additional endocrine agents are common. The increase in the number of options now available for adjuvant therapy will have important implications for the selection of the optimal sequence of endocrine agents in the treatment of recurrent breast cancer. Menopausal status is an important factor in determining the endocrine therapy that a patient receives. For premenopausal women, tamoxifen and/or a luteinizing hormone-releasing hormone agonist such as goserelin ('Zoladex') are both options for adjuvant endocrine treatment. After progression on adjuvant and first-line tamoxifen, ovarian ablation is an appropriate second-line therapy. For premenopausal women who have undergone ovarian ablation, the use of third-line therapy with an AI becomes possible. For postmenopausal women, a wide choice of endocrine treatment options is available and an optimal sequence has yet to be determined. Options for first-line therapy of metastatic disease include an AI for women who have received adjuvant tamoxifen or tamoxifen for patients who have received adjuvant anastrozole. In addition, data suggest that fulvestrant ('Faslodex'), a novel estrogen receptor (ER) antagonist that downregulates the ER protein and has no known agonist effects, is a promising therapeutic option that has shown efficacy in the treatment of postmenopausal women with advanced breast cancer. Other agents that may be used in the sequence include the steroidal AI exemestane and the progestin megestrol acetate. The widening range of adjuvant endocrine options therefore represents an opportunity to prolong patient benefits in the treatment of hormone receptor-positive breast cancer, and will require the further refinement of the optimal sequence of endocrine agents for the treatment of recurrent breast cancer.
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PMID:Sequential hormonal therapy for metastatic breast cancer after adjuvant tamoxifen or anastrozole. 1453 31

This article evaluates the use of early hormonal therapy in patients with localised or locally advanced prostate cancer. In patients receiving radiotherapy, an overall survival benefit is proven for adjuvant goserelin ('Zoladex') in locally advanced disease. Adjuvant to radical prostatectomy, castration (goserelin or orchiectomy) has demonstrated an overall survival benefit in patients with lymph node metastases. Survival advantages have not yet been proven with nonsteroidal antiandrogens, but immediate or adjuvant bicalutamide ('Casodex') improves objective progression-free survival in patients with locally advanced disease, with certain quality-of-life advantages over castration.
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PMID:Evaluating the use of early hormonal therapy in patients with localised or locally advanced prostate cancer. 1585 51

LHRH analogs have become a promising modality in prostate cancer therapy as an alternative to surgical castration, and the use of these agents is generally considered to be safe. Since now, only few cases of an apoplexy of previously undiagnosed pituitary adenoma (usually gonadotropinoma) at the beginning of therapy have been described in the medical literature. We present a case of a 74 year old patient who was diagnosed of prostate cancer at the age of 68. There was no evidence of metastatic disease. Radical prostatectomy was performed and LHRH analog gosereline (Zoladex 3.6 mg s.c.) was administered. During the first day after gosereline injection the patient developed headaches that became more severe over the next 3 days. Then the patient experienced nausea and vomiting, double vision and eyelid ptosis. On the 5th day the patient temporarily lost consciousness and was admitted to hospital. Imaging (computerized tomography, magnetic resonance imaging) revealed the presence of a pituitary tumor and hemorrhage within the gland. There was no evidence of pituitary dysfunction in hormonal studies. Neurosurgical intervention was postponed for 5 days after admission. Pathological mass with signs of recent hemorrhage was removed via transsphenoidal route. The tumor had negative immunohistochemical GH, ACTH and PRL staining. Neurological impairment resolved within 9 months after the operation. As a result the patient required adrenal and thyroid replacement. During 6 years of follow-up there was no evidence of prostate cancer recurrence.
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PMID:Apoplexy of clinically silent pituitary adenoma during prostate cancer treatment with LHRH analog. 1715 26


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