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)

In two groups of patients with disseminated testicular carcinoma the effect of combination chemotherapy on the pituitary-gonadal axis was evaluated, after unilateral orchiectomy: The two groups comprised 15 patients without hCG-producing metastases (group A), and 14 patients with hCG-producing metastases (group B). Seven patients who had received no chemotherapy were studied one year after unilateral orchiectomy as a control group (group C). In group A, serum levels of testosterone and oestradiol increased during chemotherapy, as did the levels of LH and FSH. The serum LH and FSH response to LHRH was increased following chemotherapy, whereas the serum testosterone increase after hCG stimulation remained unchanged. A rise of 316% in SHBG binding capacity was found after chemotherapy. This presumably accounted for the elevated steroid levels in the presence of high gonadotrophin levels, but unaltered Leydig cell response. The elevated serum levels of testosterone and oestradiol and the suppressed serum FSH levels normalized during disappearance of ectopic hCG production in group B patients. Leydig cell refractoriness to hCG and the FSH response to LHRH also reverted to normal. After chemotherapy, FSH, but not LH levels exceeded those of group C patients, presumably as a result of the azoospermia induced by chemotherapy. The hormonal changes associated with chemotherapy are best explained by an increase in serum binding proteins, notably SHBG.
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PMID:Leydig cell function in patients with testicular cancer during and after chemotherapy. 642 50

We compared the efficacy and safety of the gonadotropin-releasing hormone analogue, leuprolide (1 mg subcutaneously daily), with diethylstilbestrol (DES, 3 mg by mouth daily) in patients with prostate cancer and distant metastases (Stage D2) who had not previously received systemic treatment. Initial therapy (leuprolide or DES) was continued for as long as an objective response was noted; cross-over to the alternative arm occurred at the time of disease progression or intolerable adverse reactions. Ninety-eight patients were randomly assigned to leuprolide, and 101 to DES. Suppression of testosterone and dihydrotestosterone and decreases in acid phosphatase were comparable in the two groups. Patients receiving DES experienced more frequent painful gynecomastia (P less than 0.00001), nausea and vomiting (P = 0.02), edema (P = 0.008), and thromboembolism (P = 0.065) than those receiving leuprolide. The leuprolide group reported more "hot flashes" (P = 0.00001). Overall, 86 per cent of the leuprolide group had an objective response (complete response, 1 per cent; partial response, 37 per cent; stable disease, 48 per cent), as compared with 85 per cent of the DES group (complete, 2 per cent; partial, 44 per cent; stable, 39 per cent). Actual survival rates at one year were 87 per cent for the leuprolide group and 78 per cent for the DES group (P = 0.17). We conclude that leuprolide offers an important alternative treatment that is therapeutically equivalent to and causes fewer side effects than DES for the initial systemic management of metastatic prostate cancer.
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PMID:Leuprolide versus diethylstilbestrol for metastatic prostate cancer. 643

This report describes a virilizing granulosa cell tumor in a postmenopausal woman. The tumor metastasized to the liver, urinary bladder, and spinal column. Although the bladder metastases were diagnosed initially as paraganglioma, review of the slides and the demonstration of abundant lipid within the tumor cells led to the correct diagnosis. The plasma testosterone and 17-hydroxyprogesterone levels were elevated, while the plasma 17-hydroxypregnenolone and dehydroepiandrosterone levels were normal, suggesting that the delta 4-pathway of testosterone biosynthesis was predominant in this tumor. Gonadotropin levels were suppressed and did not respond to gonadotropin-releasing hormone. Presumably, this suppression was due to an increase in the plasma testosterone level.
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PMID:Virilization due to a metastasizing granulosa cell tumor. 664 52

In order to block the influence of androgens from all sources on the growth of prostatic cancer, we have used a new hormonal therapy based on medical castration achieved with the potent LHRH agonist [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide (HOE-766) combined with the administration of a pure antiandrogen that neutralizes the action of adrenal androgens as well as those still secreted in low amounts by the testis during LHRH agonist treatment. This study was performed in ten patients with advanced prostatic carcinoma (9 at stage D2 and one at stage C). Bone pain, prostatism and general well-being were 60 to 90% improved within one month after starting treatment in all patients. After 2 months of treatment, minimal bone pain remained only in one patient who was originally bedridden. Bone scanning showed a 70 to 90% decrease in uptake after 3 to 5 months of treatment in the patients studied. Acid phosphatase levels were 60 to 90% reduced after 2 months of treatment in 3 out of the 4 patients who had elevated levels before therapy. Marked objective and subjective improvement was thus rapidly observed in 9 out of 10 patients treated with the combined therapy, while, in the other patient at stage C, subjective improvement could be documented. Although preliminary, this study indicates that a combined hormonal therapy which neutralizes all androgenic influences on peripheral tissues is of potential benefit in prostatic cancer. Moreover, the ease of application as well as the lack of secondary effects of the present approach should make possible its use early in the disease and should thus minimize the development of metastases and androgen-resistant cell clones. Randomized prospective studies on this potentially beneficial therapy are warranted.
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PMID:New hormonal therapy in prostatic carcinoma: combined treatment with an LHRH agonist and an antiandrogen. 681 1

A case is presented of a middle-aged man suffering from stage D2 prostate cancer with pulmonary metastases who responded favorably, first, to endocrine combination therapy with the antiandrogen flutamide and an LHRH agonist for 5.5 years, and, second, to the subsequent withdrawal of Flutamide at the time of the progression of the disease. This case has several exceptional features: absence of bone metastases, pulmonary metastatic nodules characterized as focal neuroendocrine differentiation, and a positive response to antiandrogen withdrawal upon relapse of metastases after initial positive response. The concept of escape to androgen blockade and development of androgenic hypersensitivity is discussed.
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PMID:Metastatic prostate cancer pulmonary nodules: beneficial effects of combination therapy and subsequent withdrawal of flutamide. 751 17

Hormonotherapy, the oldest known effective medical treatment for breast cancer, is still widely used today. The effectiveness of numerous hormone (anti-oestrogen) treatments for breast cancer, with tumour regression reaching about 30% of the advanced forms or more in hormono-dependent forms identified by tumour hormone receptor assays has been demonstrated. Castration by surgery, radiotherapy or anti-LHRH agents is still proposed as one of the possible suppressive treatments. The other type of hormone management currently used is the anti-oestrogen agent tamoxifen which is general well tolerated. High doses of synthetic progesterones or anti-aromatase agents such as aminoglutethimide are also prescribed. These treatments require a less well tolerated association with hydrocortisone or corticosteroid treatments. Indications for hormonotherapy have become quite precise. As an adjuvant, castration before menopause and tamoxifen after menopause have been shown to be important methods in a meta-analysis published in 1992. The role of each of these treatments as part of an overall chemotherapy management is yet to be determined. In cases with metastases, hormonotherapy, whatever the modality used, is still particularly useful in elderly women with positive hormone receptor assays.
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PMID:[Hormone therapy in breast cancer]. 776 20

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

Maximal androgen blockade (MAB), the eradication of the effects of adrenal androgens on prostate cancer cells after castration, has been used with differing success in the treatment of prostatic carcinoma. The aim of this randomized phase III study was to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist (LHRH-A) depot formulation, goserelin acetate (3.6 mg s.c. once every four weeks), and flutamide (250 mg three times daily), in patients with metastatic cancer. Treatment usually continued until disease progression (or for a minimum of three months). Efficacy was assessed by response, time to disease progression, and duration of survival. Clinical evaluations, standard laboratory tests, and imaging examinations were carried out regularly. A total of 327 patients were entered in this study. There was a difference in response only for prostatic acid phosphatase (PAP) with a more frequent decrease of the serum values to normal in the serum in patients assigned to MAB treatment. The MAB treatment, however, proved significantly better for time to subjective progression, time to objective progression, time to first (subjective and objective) progression, and duration of survival. The most frequent side effects for both treatments included hot flushes and gynecomastia. In conclusion, significant time to progression and survival benefits are achieved by adding flutamide to an LHRH-A regimen, probably improving the quality of life of patients with metastatic cancer.
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PMID:Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). EORTC GU Group and EORTC Data Center. 836 20

Hormonal therapy represents first-line treatment for patients with advanced prostate cancer. Generally, surgical castration is viewed as the 'gold standard' but carries with it a psychological effect. Medical alternatives include LHRH analogues, antiandrogens, and oestrogens, though the last of these is associated with cardiovascular problems. For complete androgen ablation, it is generally believed that androgens of both testicular and adrenal origin need to be blocked. Combined androgen blockade (CAB) by the addition of antiandrogen to castration (medical or surgical) may, therefore, be an appropriate treatment for advanced prostate cancer. Recent trials have shown that CAB may have treatment advantages compared with castration alone, and these benefits are greatest in patients with minimal metastatic disease. For these patients CAB may now be considered as standard therapy. In the treatment of non-metastatic disease, recent trends based on the experience gained in advanced prostate cancer include the possible use of hormonal therapy in neoadjuvant and adjuvant settings along with prostatectomy or radiotherapy. There is also growing interest in the use of intermittent rather than continuous hormonal therapy. New treatments offer an increasing range of management options to help improve the quality of life of prostate cancer patients.
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PMID:Advances and trends in hormonal therapy for advanced prostate cancer. 853 70

Endocrine therapies for breast cancer have been used for more than a century. The concept that changing the hormonal balance of the patient with breast cancer could lead to changes in tumor growth and regression of metastatic disease was recognized even before hormones and endocrine agents were available. Ablation of ovaries, adrenals, or hypophysis was used in advanced disease to obtain tumor regression and control of symptoms. Ovarian ablation was also tested for operable breast cancer showing a significant beneficial treatment effect. Several endocrine agents have been developed in recent years: estrogens, androgens, progestins, antiestrogens, aromatase inhibitors, gonadotropin-releasing hormone analogs, antiprogestins, and antiandrogens. The use of some of these agents in advanced disease led to investigations in early breast cancer: tamoxifen was the drug which was most extensively tested, showing a significant long-term benefit for treated patients. Progestins (medroxyprogesterone acetate) and aromatase inhibitors (aminoglutethimide) were also tested in a few clinical trials, but no conclusive recommendations for their use in patients with operable disease may be formulated. The most important current challenges for the appropriate use of endocrine therapies in breast cancer include (1) understanding the effect of endocrine therapies and the mechanisms of resistance associated with their use; (2) developing new agents with novel endocrine antitumor effect; (3) defining the best way to combine endocrine agents with cytotoxics or with other endocrine manipulations; and (4) identifying long-term effects of endocrine agents in terms of disease control and prevention, as well as desirable and undesirable side effects.
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PMID:Endocrine therapies of breast cancer. 875 75


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