Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151825 (bone pain)
 3,118 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leuprorelin (leuprolide acetate) is a synthetic analogue of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH)] which initially stimulates luteinising hormone (LH) and hence testicular androgen release; continuous administration then results in profound suppression of these hormones. Testosterone levels associated with castration are attained within 3 to 4 weeks. A biodegradable subcutaneous or intramuscular depot formulation of leuprorelin 3.75 or 7.5 mg, which releases the drug at a constant rate over 28 days, is available and may be preferred over daily subcutaneous injections. The progression of previously untreated advanced prostatic cancer is delayed in 70 to 90% of men receiving leuprorelin, with median survival of approximately 2 years. The efficacy of leuprorelin is equivalent to that of estrogen therapy, but the tolerability of the GnRH analogue is far better. In contrast to most other studies of GnRH agonists, a slight survival advantage has been reported for combined treatment with leuprorelin and the antiandrogen flutamide. Small noncomparative trials reveal that leuprorelin also causes regression of benign hyperplastic prostate tissue with corresponding relief of obstructive, but not irritative, symptoms although continuous treatment is necessary to maintain remission. Impotence and flushing occur in most leuprorelin recipients but, unlike diethylstilbestrol (stilboestrol), cardiovascular toxicity and gynaecomastia are not significant problems. Symptom flare, usually manifested as bone pain in prostate cancer patients and exacerbation of obstructive symptoms in those with benign prostatic hypertrophy, can occur in 4 to 29% at the beginning of treatment. Leuprorelin treatment is therefore an established effective palliative measure in men with previously untreated advanced prostatic cancer, and may have a role in those with benign hypertrophy who are unfit for surgery.
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PMID:Leuprorelin. A review of its pharmacology and therapeutic use in prostatic disorders. 179 35

Endocrine management is the best palliative management available for patients with carcinoma of the prostate. It is based on androgen withdrawal by castration or other means. Endocrine management was introduced into clinical medicine by Huggins and his associates in the early 1940s on the basis of careful clinical and experimental research establishing the biological effects of androgen withdrawal in animal systems and in humans. It was believed for a long time that endocrine treatment would prolong life. This, however, in spite of extensive clinical research, remains unproven. The possibility that the life span of prostate cancer patients is determined by the hormone independent cell populations within virtually all prostate cancers still remains a possibility. Endocrine treatment has, however, been shown to have a significant impact on symptoms related to prostate cancer, especially on bone pain, urethral and ureteral obstruction. It has also been shown to prolong time to progression and to death from prostate cancer. Although castration and the application of exogenous oestrogens with the purpose of interfering with pituitary testicular feedback have been standard treatment of prostate cancer for more than 30 years, new treatment methods have recently become available. Luteinizing hormone releasing hormone agonists allow suppression of plasma testosterone to castration levels without exerting the side effects associated with oestrogens (eg cardiovascular incidents, gynaecomastia). Also, the application of pure or steroidal anti-androgens allows direct counteraction of circulating androgens at the target cell. The possibility that initial suppression of adrenal androgen production, which contributes about 10% of circulating androgens in males, may be more beneficial than suppression of testicular androgens alone has been subject to intense clinical research recently. Simultaneous suppression of testicular and adrenal androgens in primary management of prostate cancer is called total androgen blockade or total androgen suppression. Up to now, however, no convincing advantages of total androgen suppression regimens above castration have been shown. Total androgen suppression seems to produce significantly better survival when compared with daily injections of LHRH alone. The use of pure anti-androgens or of 5 alpha-reductase inhibitors could potentially prevent the most significant side effect of all androgen withdrawal regimens, loss of libido and impotence. However, neither the use of pure anti-androgens as monotherapy nor the use of 5 alpha-reductase inhibitors as monotherapy has been shown to produce clinical results that are equal to castration.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Endocrine therapy: where do we stand and where are we going? 184 51

The therapeutic efficacy and safety of various doses of leuprorelin acetate depot were determined in an open, multicentre study of patients with locally advanced or metastatic prostatic cancer (stages C, D1 or D2). Patients were randomly assigned to receive 3.75 mg (30 cases), 7.5 mg (eight cases), 15 mg (eight cases) and 30 mg (one patient) leuprorelin acetate depot administered subcutaneously once every 4 weeks. Of the 43 patients evaluable, two (5%) had complete remission, 23 (53%) partial remission and 13 (30%) patients stable disease. No significant differences were observed in response rates in relation to dose, disease stage or previous hormonal therapy. Disappearance or improvement in bone pain and urinary symptoms occurred in 63% and 79% of cases, respectively. Serum androgen concentrations decreased rapidly and persistently to castration levels, without significant differences for different doses. Treatment was well tolerated with a low incidence of mild side-effects - gynaecomastia (16%), nausea/vomiting (13%) and diarrhoea (2%). It is concluded that 3.75 mg leuprorelin acetate depot given subcutaneously once every 4 weeks is able to produce hormonal effects in all patients, an overall objective response comparable to that obtained using higher doses.
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PMID:Leuprorelin acetate depot in advanced prostatic cancer: a phase II multicentre trial. 210 83

In a randomized, prospective trial, 199 previously untreated patients with Stage D2 prostatic cancer were treated with 3 mg/day diethylstilbestrol (DES) or 1 mg/day leuprolide acetate, a luteinizing hormone releasing hormone analog. Both DES and leuprolide suppressed testosterone to the desired castrate levels. Objective measures of disease, such as acid phosphatase levels, and subjective measures, such as bone pain, performance status, and mobility, showed similar decreases in both groups. No progression of disease was seen in 86 per cent of the leuprolide-treated group, compared with 85 per cent of the DES-treated group. The time to disease progression, development of adverse reaction requiring discontinuation of treatment, or death was identical for the two groups. Hot flashes were more common with leuprolide than with DES. Gynecomastia and breast tenderness, nausea and vomiting, and peripheral edema occurred more often in the DES group. Of those taking DES, 13 per cent discontinued treatment because of side effects, compared with 3 per cent of those taking leuprolide.
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PMID:Leuprolide versus diethylstilbestrol for previously untreated stage D2 prostate cancer. Results of a prospectively randomized trial. 307 35

In a controlled, prospective, randomized clinical trial, we evaluated the safety and efficacy of leuprolide, a superactive analog of luteinizing hormone releasing hormone, given in a single subcutaneous injection dose of 1 mg per day, versus diethylstilbestrol (DES) 3 mg per day by mouth in patients with previously untreated Stage D2 prostatic adenocarcinoma. Eleven leuprolide patients and 10 DES patients were evaluated for therapeutic response. Eighty per cent of patients in each group experienced subjective improvement in bone pain and urinary obstructive signs and symptoms. Although the pooled percentages of complete, partial, and stable objective responses were greater for the leuprolide group than the DES group, the sums of the percentages of complete and partial objective responses were comparable for both treatment groups during the first forty-eight and sixty weeks of the study, respectively. In addition, patients not responding to leuprolide generally experienced no benefit with crossover to DES, and vice versa. Serious adverse reactions were more common in the DES group and included fatal myocardial infarction, arrhythmia, deep venous thrombosis, and gynecomastia. Vasomotor flushing, disease flare, and injection site irritation occurred most often in leuprolide patients, but did not require modification or discontinuation of treatment.
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PMID:Comparison of leuprolide and diethylstilbestrol for stage D2 adenocarcinoma of prostate. 392 51

Seven adult patients with cystic fibrosis who had radiological evidence of hypertrophic osteoarthropathy were reviewed. In five of the patients symptoms were particularly pronounced at times of acute infective exacerbations; appropriate treatment of the infective episodes resulted in reduction or resolution of the bone pain and joint effusions. Despite this symptomatic relief periosteal changes persisted radiologically and their chronic nature was indicated by changes in the midshafts of long bones. Four of the seven patients had transient gynaecomastia or mastalgia related to infective exacerbations. It is hypothesised that a neuroendocrine mechanism--namely, release of vasoactive intestinal polypeptide--might account for the osteoarthropathy.
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PMID:Hypertrophic osteoarthropathy in cystic fibrosis. 642 98

Improvement of quality of life (QoL) has become a major endpoint in clinical trials of patients with prostate cancer. However, there still exist considerable methodological problems regarding the development of optimal instruments and methods for presenting the results. Within the European Organisation for the Research and Treatment of Cancer (EORTC) a core questionnaire is generally used for QoL evaluation, combined with a treatment- and disease-specific module. So far, no official EORTC prostate cancer module has been developed. Previous and ongoing trials in prostate cancer have addressed the following issues: for localised prostate cancer, micturition and sexuality, and for metastatic prostate cancer, bone pain, micturition, sexuality, vitality, hot flushes and gynaecomastia. The future challenge is to incorporate QoL results into the overall evaluation of treatment in combination with survival results and economical considerations.
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PMID:Quality of life in prostate cancer: what are the issues and how are they measured? 871 74

Palliation is the principal aim of treatment for patients with advanced prostate cancer. In a strict sense, "palliation" means reduction of existing symptoms, but in clinical practice a further goal is to prolong the symptom-free interval in asymptomatic patients and to prevent distressing problems, such as pain and fatigue, with the overall aim of improving quality of life. In patients with advanced prostate cancer, quality of life parameters represent an important endpoint in clinical routine and in clinical trials. Evaluation of quality of life issues also provides independent prognostic information. A feasible approach for regular quality of life assessment is the use of a questionnaire developed for cancer patients together with psychometrically tested disease-specific and treatment-specific modules designed to evaluate the various factors, such as micturition, sexuality, vitality, and intestinal problems for localized prostate cancer, and bone pain, micturition, sexuality, hot flashes, gynecomastia, and gastrointestinal problems for metastatic prostate cancer.
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PMID:Quality of life in advanced prostate cancer. 899 83