Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Menopausal symptoms manifesting as hot flashes and sweats occur in up to 75 percent of patients following either orchiectomy or treatment with a luteinizing hormone-releasing hormone agonist for prostate cancer. As many as one third of these patients will experience symptoms severe enough to seek palliation. We treated 12 such patients with low dose diethylstilbestrol (1/3 mg daily). Nine patients demonstrated both objective and subjective improvement in their menopausal symptoms. Five patients experienced toxicity including new onset of gynecomastia or breast soreness although no patient discontinued treatment on this basis. No cardiovascular complications were noted. We conclude that low dose diethylstilbestrol is an inexpensive, effective means of controlling troublesome postorchiectomy menopausal symptoms in carefully selected patients.
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PMID:Treatment of castration-induced menopausal symptoms with low dose diethylstilbestrol in men with advanced prostate cancer. 128 87

Cyproterone acetate is a steroidal anti-androgen that blocks the androgen-receptor interaction and reduces serum testosterone through its weak anti-gonadotropic action. It can be regarded as the only anti-hormone that causes complete androgen blockade as monotherapy. Many animal experiments and several clinical phase II and phase III trials have demonstrated that it deserves a place in the endocrine therapy of advanced prostate cancer, particularly for those patients who find orchidectomy unacceptable and who do not have known cardiovascular risks. Additionally, cyproterone acetate can be used safely to prevent disease flare when a luteinizing hormone releasing hormone analog is the drug of choice and to suppress hot flashes in response to LHRH agonists or after orchidectomy.
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PMID:The position of cyproterone acetate (CPA), a steroidal anti-androgen, in the treatment of prostate cancer. 153 52

Casodex, a pure potent non-steroidal anti-androgen, has been shown in a phase II clinical trial program to be very well tolerated and to have fewer side-effects compared with other anti-androgens. The most commonly reported side-effects (prompted by direct questioning) were breast tenderness (63.4%), breast swelling (52.5%), and hot flashes (23.6%). Gastrointestinal disturbances, hepatic impairment, alcohol intolerance, and problems with light adaptation are not associated with Casodex treatment. In this study, Casodex (50 mg once daily) was evaluated in 267 patients, 130 of whom have received it for more than 1 year. On assessment of best objective response, 55.5% of patients showed partial regression, 15.6% stable disease, 17.1% progression, and 11.8% were not assessable. These results are comparable with other standard hormonal therapies for advanced prostate cancer.
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PMID:Casodex: a pure non-steroidal anti-androgen used as monotherapy in advanced prostate cancer. 157 64

We report preliminary results for the first 164 patients enrolled in a multicenter study comparing the endocrine effects, efficacy, and safety of 3.6 mg of goserelin acetate (Zoladex) and orchiectomy in patients with Stage D2 prostate cancer. Eighty-one patients were randomly allocated to receive Zoladex and 83 to orchiectomy. The median follow-up time for all patients was two hundred ten days. Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dL) within four weeks in both groups and remained suppressed for up to sixty weeks. An objective response according to modified criteria of the National Prostatic Cancer Project was observed in 81 percent and 78 percent of patients in the Zoladex and orchiectomy groups, respectively. There were no statistically significant differences between treatment groups in the distributions of time to treatment failure or time to disease progression. The most commonly reported adverse events in both treatment groups were hot flashes, cancer-related pain, unspecified pain, and urinary symptoms. These results suggest that Zoladex may offer an alternative to orchiectomy in the treatment of advanced prostate cancer.
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PMID:Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Zoladex Prostate Study Group. 182 32

Goserelin acetate implant is a newly approved depot formulation of a luteinizing hormone-releasing hormone (LHRH) agonist indicated for palliation of advanced prostate cancer. LHRH superagonists suppress gonadotropin release from the pituitary gland by causing down-regulation of receptors. The sustained-release dosage form contains goserelin acetate dispersed in a biodegradable copolymer matrix and is designed to release active drug over 28 days. Pharmacokinetic studies have demonstrated that, despite nonzero order release of goserelin from the matrix, goserelin acetate implant maintains serum concentrations of testosterone in the range normally found in castrated men (less than 2 nmol/L) throughout the recommended 28-day dosing interval. Response rates similar to those for orchiectomy and estrogen administration have been demonstrated. Combination therapy with either diethylstilbestrol or flutamide has produced favorable results, although the major advantage appears to be a reduction in the tumor flare seen during the first week of LHRH agonist therapy rather than an increase in response rate or survival. Adverse effects are similar to other LHRH agonists and include tumor flare during the first week of therapy, decreased libido, decreased erectile potency, hot flashes, and gynecomastia. In combination with flutamide, additional adverse effects include diarrhea, nausea, vomiting, and elevated hepatic aminotransferases, all of which can be attributed to flutamide administration. Local reactions are minimal; however, some patients require a local anesthetic before goserelin acetate implant injection. The recommended dose is 3.6 mg administered subcutaneously into the upper abdominal wall every 28 days. The average wholesale cost is approximately +320 per month. Formulary addition is recommended.
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PMID:Goserelin acetate implant: a depot luteinizing hormone-releasing hormone analog for advanced prostate cancer. 183 21

Sixty one men, with advanced prostatic cancer, were entered on a trial using a nasally administered gonadotropin-releasing hormone analogue agonist, buserelin, as first line treatment. This is the first trial to use intranasal buserelin without primary injections and without antiandrogens. No 'flare' phenomenon was observed. The only side effects were hot flashes (69%) and decreased libido (25%). The response rate of 82%, with a median response duration of 16 months, compares favourably to responses reported with orchidectomy or estrogens. Serum testosterone, FSH and LH were monitored at regular intervals. Mean serum testosterone baseline values of 15 nmol/L decreased to castrate levels, and remained low while patients were on study. It is concluded that intranasal buserelin is an effective, simple and safe method to achieve androgen deprivation and is an alternative to orchidectomy in the treatment of advanced prostatic cancer.
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PMID:Long term follow-up of patients with advanced prostatic cancer treated with nasal buserelin. 190 43

A collaborative multicenter trial was conducted by 17 Italian groups to verify whether the so-called total androgen blockade obtained with luteinizing hormone releasing hormone (LHRH) analogs combined with antiandrogens is more effective than conventional monotherapy in the treatment of advanced prostatic cancer. A total of 328 previously untreated patients were evaluated: 163 patients received Zoladex depot alone, 3.6 mg subcutaneously every 28 days, and 165 patients received Zoladex depot plus cyproterone acetate (CPA), 200 mg/day orally. The follow-up period ranged from 41-251 weeks. Treatment was well tolerated, and side-effects in both groups mainly comprised loss of libido and erections, hot flashes and breast swelling and tenderness. There was no significant difference in objective response after 6, 12 and 24 months of treatment between the 2 groups. Median time to disease progression was comparable in both groups: 55 weeks in the Zoladex group and 54 weeks in the Zoladex plus CPA group. The time to disease progression and the survival distribution was comparable in both groups. Although there were no significant differences in the overall subjective response to both treatments, a faster improvement, with respect to pain and performance status was noted in the Zoladex plus CPA group (8 weeks) compared to Zoladex alone (12 weeks). The addition of antiandrogen, by inhibiting the initial elevation of plasma testosterone, may prevent the disease flare-up which occurs in a small number of patients during the first few days of treatment with LHRH analogs alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Zoladex vs. Zoladex plus cyproterone acetate in the treatment of advanced prostatic cancer: a multicenter Italian study. 215 Dec 78

Flutamide is a nonsteroidal pure antiandrogen that acts by inhibiting the uptake and/or binding of dihydrotestosterone to the target cell receptor, thus interfering with androgen action. Flutamide is well absorbed orally and extensively metabolized; its active metabolite, 2-hydroxyflutamide, is formed rapidly and excreted almost entirely by the kidneys. Clinical studies in prostate cancer patients have demonstrated efficacy with flutamide monotherapy in patients who had received no prior treatment, in untreated patients with combined androgen blockade concomitantly with a luteinizing hormone-releasing hormone (LHRH)-agonist, and in relapsed patients. A randomized, placebo-controlled trial demonstrated a 26 percent increase in median survival for patients treated with leuprolide plus flutamide compared with leuprolide plus placebo. When given as monotherapy and in combination with an LHRH-agonist, flutamide is well tolerated. The usual adverse effects are gynecomastia and mild diarrhea when given as a single agent. In combination with an LHRH-agonist, hot flashes, loss of libido, impotence, mild nausea and vomiting, gynecomastia, and diarrhea are commonly reported. However, only diarrhea occurred more frequently in patients treated with leuprolide plus flutamide than in those treated with leuprolide plus placebo. Flutamide is indicated in combination with an LHRH-agonist (e.g., leuprolide) as initial therapy in metastatic (stage D2) prostate cancer. The usual dose is 250 mg po tid given at eight-hour intervals and started concurrently with the LHRH-agonist. Formulary addition is recommended.
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PMID:Flutamide: an antiandrogen for advanced prostate cancer. 219 61

Leuprolide is the first member of the class of gonadotropin-releasing hormone (GnRH) agonist analog to be released in the U.S. The pharmacology of leuprolide is complex and not yet completely defined. This agonist analog is more potent than natural GnRH and appears to be capable of occupying pituitary GnRH receptors. This results in a "down regulation" of the receptors' activity and gonadotropin release, ultimately decreasing serum testosterone levels to those seen following castration. Leuprolide has been found effective in the palliative treatment of advanced cases of prostatic cancer and is not associated with the cardiovascular and thromboembolic toxicity seen with conventional diethylstilbestrol therapy. Leuprolide is administered by daily subcutaneous injections and has been generally well tolerated. The most common adverse effects are hot flashes and a possible flare-up of prostatic carcinoma symptoms on initial dosing. As clinical experience grows in the use of GnRH agonist analog, GnRH will assume a greater role in the treatment of metastatic prostatic cancer.
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PMID:Leuprolide: a gonadotropin-releasing hormone analog for the palliative treatment of prostatic cancer. 242 15

Twenty-two patients with newly diagnosed advanced prostatic cancer treated with once-monthly subcutaneous injection of a long acting depot preparation of a new luteinizing hormone-releasing hormone superagonist (ICI 118,630) with a minimum follow-up duration of 6 months are reported. The partial regression rate was 45.4% while 36.4% of the patients had stable disease and only 18.2% have progressed by P.O.N.CA.P. criteria. Patient acceptance was excellent and side effects occurring during treatment (hot flashes, gynecomastia, etc.) were minimal. The depot preparation of the LH-RH analogue was well tolerated and no side effects required dose modifications or removal from the study. Depot LH-RH analogue may become an alternative treatment for patients with advanced prostatic cancer if further clinical evolutions will confirm that the response rate with LH-RH analogue is comparable to the conventional endocrine therapies.
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PMID:[Treatment of advanced prostatic carcinoma with a depot LH-RH analog (ICI 118630)]. 252 15


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