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

Twenty patients with advanced prostate cancer have been treated with an intermittent endocrine therapy schedule. Hormone therapy (diethylstilbestrol in 19 patients and flutamide in 1 patient) was administered until a clinical response was clearly demonstrated and then it was withheld until symptoms recurred. Prior to treatment 17 of 20 patients had bone pain and positive radionuclide scans, two had asymptomatic pulmonary metastases, and one had symptomatic localized disease. Duration of endocrine therapy prior to withdrawal of all treatment ranged 2 to 70 months (median, 10 months). Disease progression occurred 1 to 24 months (median, 8 months) after interruption of therapy. All patients who relapsed had a rapid clinical response following resumption of endocrine therapy. Nine of ten patients rendered impotent by endocrine therapy resumed sexual activity within 3 months of stopping treatment. This data indicates that satisfactory palliation of advanced prostatic cancer can be achieved in selected patients using intermittent endocrine therapy.
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PMID:Intermittent endocrine therapy for advanced prostate cancer. 2823 8

D-Trp-6-LH-RH, a long acting LH-RH agonist was given in a phase II trial to 85 patients aged 52 to 88 (mean 69) with advanced prostatic carcinoma, stage B (8 pts), C (9 pts) and D (68 pts). Twenty-five patients were previously untreated, 40 had received previous hormonal therapy but none was considered has having hormone resistant tumor; 20 patients had received surgery or radiotherapy or both. D-Trp-6-LH-RH was given s.c. at a daily dose of 500 micrograms during the first seven days, followed by 100 micrograms daily. Antitumor activity was assessed after 90 days and treatment was continued in responders. The results were the following: plasmatic levels of LH were sharply decreased and those of testosterone were in all cases under 1 ng/ml by the 90th day of treatment; urinary symptoms and bone pain disappeared or were greatly improved in almost all patients; the volume of the prostate measured by ultrasonography and/or computerized tomography regressed by more than 50% of initial volume in 44% of the 34 patients for which this parameter was evaluable; bone scintiscans were improved in 18% of evaluable patients; plasmatic levels of prostatic acid phosphatases determined by radio immuno-assay were elevated in 28 patients, 61% of which presented a decrease superior to 50% or normalisation of this parameter. No disease flare up was observed on initiation of therapy. Impotence was constant but reversible on discontinuation of therapy. No other side effect could be attributed to therapy.
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PMID:[Advanced cancer of the prostate. Treatment with an LH-RH agonist, D-Trp-6-LH-RH]. 243 Jun 52

In this pilot study the treatment of advanced prostatic cancer with cyproteronacetate (AndrocurR) is compared with the treatment of a lower dose cyproteronacetate plus lisuride (DoperginR), an anti-prolactin derivative. Treatment was continued until progression and/or the appearance of serious side effects necessitated termination. The duration of the treatment with cyproteronacetate plus lisuride ranged from 2 to 38 months. Most cases showed a partial response, evaluated on the basis of lower levels of prostatic acid phosphatase, relief of bone pain and reduction of bone metastases. Serious side-effects other than impotence did not occur.
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PMID:Treatment of advanced prostatic cancer with anti-androgens alone and a combination of anti-androgen with anti-prolactin--a pilot study. 294 68

Various approaches to hormonal treatment of prostate carcinoma are discussed. Eighty-one patients with prostatic carcinoma, eight with stage B, nine with stage C, and 64 with stage D disease, were treated subcutaneously daily for 3 months with the LH-RH agonist D-Trp-6-LH-RH (Decapeptyl) in order to evaluate the incidence of remissions according to WHO recommendations for oncologic trials. The findings were compared to those obtained with other hormonal therapies of prostatic carcinoma according to the statistical method of "expected response rate" as adapted by Lee and Wesley for phase II trials. Treatment with D-Trp-6-LH-RH greatly reduced serum LH and testosterone levels without raising serum prolactin. After 1-2 weeks of therapy, there was relief of subjective symptoms and a reversal of the signs of prostatism as well as a marked decrease in bone pain. At 90 days 52 patients had complete relief of prostatism and 21 had only mild signs and symptoms. Seventy patients were experiencing no bone pain and an additional six had only mild pain. Prostatic size, evaluated by rectal examination and transabdominal ultrasonography, reverted to normal in 26.4% of patients (complete remission) and was reduced by more than 50% in an additional 17.6% (partial remission), the overall rate of complete plus partial regression of prostatic enlargement being 44%. Scans showed a major improvement of bone lesions in 14.8% of cases. This response increased to 37% after more than 6 months of follow-up. Prostatic acid phosphatase levels were decreased by more than 50% in 61% of the patients, but this test appears to be a less valid marker than the lipid-associated sialic acid (LASA). The increase in LASA before treatment and a reduction after treatment can frequently be correlated with the objective volume of the neoplasms. No flare-up of the disease was encountered, and there were no side effects except for impotence. Statistical analyses of results by the method of Lee and Wesley indicated that the incidence of complete and partial regression (CR and PR) observed with D-Trp-6-LH-RH was not significantly different from that recorded in previous studies for another LH-RH analog, Buserelin. However, CR and PR obtained with D-Trp-6-LH-RH (44%) were significantly higher than with subcapsular orchiectomy (22%). Hormonal effects and some other actions of D-Trp-6-LH-RH were compared and contrasted with those produced by castration, estrogens, antiandrogens, and progestogens.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Phase II trial with D-Trp-6-LH-RH in prostatic carcinoma: comparison with other hormonal agents. 294 53

Adenocarcinoma of the prostate (CaP) in the Western world has become the most common noncutaneous human tumor. CaP is also the second most important cause of cancer deaths among the male population in the United States. Major progress was made in the past decade in better understanding this disease process, as well as in improved diagnostic accuracy. This improved diagnostic accuracy was due to wide application of prostate-specific antigen (PSA), use of transrectal ultrasound (TRUS), and greater awareness among clinicians of CaP. The use of PSA in clinical practice has resulted in a sharp increase in the number of patients diagnosed with capsule-confined tumors. The optimal treatment for capsule-confined CaP is in the process of being defined. Radical prostatectomy in the United States is currently the most commonly applied treatment for younger patients. Excellent treatment results with a 10-year actuarial survival > 80% are readily obtainable in properly selected patients. Nerve-sparing procedures helped reduce the high incidence of impotence that occurs in patients after radical retropubic prostatectomy. Radiotherapy remains the other curative treatment method in the management of CaP patients, with long-term survival rates similar to those reported in surgical series. Due to the problem of frequent preoperative tumor understaging, a routine use of postoperative irradiation to the prostatic fossa produces an excellent (> 95%) incidence of local tumor control. Management of patients with metastatic disease has undergone a considerable evolution with the development of modern hormonal management and treatment with strontium-89 to control intractable bone pain. Newer treatment methods such as hyperthermia are currently being investigated. Major efforts are directed toward the reduction of short- and long-term treatment toxicity associated with surgery, radiotherapy, and hormonal management, thus improving patient quality of life.
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PMID:Adenocarcinoma of the prostate: innovations in management. 912 81