cyproterone and Prostatic-Neoplasms

Prostate cancer sometimes metastasizes, especially to bone, which may cause pain, fractures and spinal cord compression. What are the best first-line treatment options for patients with metastatic prostate cancer? To answer this question, we conducted a review of the literature, using the standard Prescrire methodology. Suppressing androgen secretion by surgically removing the testicles (orchiectomy) or by administering a gonadorelin agonist relieves the pain associated with bone metastases in about 80% of patients. This treatment has a clear impact on symptoms, despite the lack of clinical trials versus placebo or no treatment. Its impact on overall survival is uncertain. In terms of survival, goserelin therapy appears to have similar efficacy to orchiectomy. The efficacy of other gonadorelin agonists is less well documented. Degarelix, a gonadorelin antagonist, does not appear to provide a therapeutic advantage over gonadorelin agonist. In 2012, oestrogen should not be used in the treatment of metastatic prostate cancer, because of its cardiovascular adverse effects. Antiandrogen monotherapy, preferably with flutamide, appears to be less beneficial than orchiectomy in terms of survival. Overall, adverse effects are more frequent with nonsteroidal antiandrogens than with gonadorelin agonists, but sexual dysfunction is less frequent. Cyproterone, a steroidal antiandrogen, seems to have fewer adverse effects leading to treatment discontinuation than nonsteroidal antiandrogens. There is no firm evidence that starting hormonal therapy before metastases become symptomatic is beneficial. When symptoms have disappeared and the PSA level is low, one option is to temporarily interrupt gonadorelin agonist therapy if it is poorly tolerated, even though this may shorten survival by a few months. The addition of a nonsteroidal antiandrogen to androgen suppression therapy slightly improves 5-year survival, preventing about 3 deaths per 100 patients, but at a cost of additional adverse effects. First-line hormonal treatments are initially very effective in relieving symptoms of metastatic prostate cancer. Our analysis of the available data suggests that the best treatment option is androgen suppression with goserelin. Flutamide monotherapy is an alternative for some patients.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Neoplasms; Cyproterone; Estrogens; Flutamide; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Practice Guidelines as Topic; Prostatic Neoplasms; Time Factors; Treatment Outcome

In advanced prostate cancer, androgen suppression (AS) by surgery or drugs controls testicular hormone secretion, and the further addition of an antiandrogen such as nilutamide, flutamide, or cyproterone acetate is referred to as maximum androgen blockade (MAB). The aim of this overview was to compare the effects on the duration of survival of MAB and of AS alone.. The collaborative meta-analysis of 27 randomised trials involved central reanalysis of the data on each of 8275 men (98% of those ever randomised in trials of MAB vs AS) with metastatic (88%) or locally advanced (12%) prostate cancer. Half were over 70 years of age, and follow-up was typically for about 5 years.. 5932 (72%) men have died; of the deaths for which causes were provided, about 80% were attributed to prostate cancer. 5-year survival was 25.4% with MAB versus 23.6% with AS alone, a non-significant gain of 1.8% (SE 1.3; logrank 2p=0.11). There was no significant heterogeneity in the treatment effect (MAB vs AS) with respect to age or disease stage. The results for cyproterone acetate, which accounted for only a fifth of the evidence, appeared slightly unfavourable to MAB (5-year survival 15.4% MAB vs 18.1% AS alone; difference -2.8% [SE 2.4]; logrank 2p=0.04 adverse), whereas those for nilutamide and flutamide appeared slightly favourable (5-year survival 27.6% MAB vs 24.7% AS alone; difference 2.9% [SE 1.3]; logrank 2p=0.005). Non-prostate-cancer deaths (although not clearly significantly affected by treatment) accounted for some of the apparently adverse effects of cyproterone acetate.. In advanced prostate cancer, addition of an antiandrogen to AS improved the 5-year survival by about 2% or 3% (depending on whether the analysis includes or excludes the cyproterone acetate trials), but the range of uncertainty as to the true size of this benefit runs from about 0% to about 5%.

Topics: Aged; Androgen Antagonists; Cyproterone; Flutamide; Humans; Imidazoles; Imidazolidines; Male; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Analysis

Prostatic cancer is the second most common cause of cancer death in males. Treatment by radical prostatectomy and radiotherapy is useful in the early stages of the disease. Whenever metastases occur, patients are usually treated by surgical (orchidectomy) or medical [gonadotropin releasing hormone (GnRH) analogue] castration. This form of treatment is, however, associated with unwanted adverse effects, such as flushing, loss of libido and potency and all patients ultimately escape therapy after a delay of 1 to 2 years. For this reason antiandrogens have been developed as another means of endocrine ablation therapy. Antiandrogens fall in 2 groups of which the first group, the steroidal antiandrogens such as cyproterone acetate (CPA), have a direct blocking effect at the cellular level but also inhibit testosterone production by their additional gestagenic properties blocking gonadotropin secretion. Except in preventing the flare-up associated with the start of GnRH analogue therapy and in reducing flushing, no evidence exist of any superiority for CPA over classical therapy in terms of adverse effects and survival. The second group, the nonsteroidal or 'pure' antiandrogens, only block androgens at the cellular level without any central effects. In contrast with other forms of castration, patients on pure antiandrogens as monotherapy preserve their sexual function and potency, at the expense of a slightly inferior androgen blockade and gynecomastia. These latter effects are explained by a compensatory rise in androgens as a result of the blockade at the central level, which weakens the androgen blockade, and by peripheral aromatisation of the increased androgens to oestrogens. In addition, some evidence exist that pure antiandrogens improve survival if combined with other forms of castration as they also inhibit the adrenal androgens, the so-called maximal androgen blockade (MAB). If patients escape control under MAB, a trial of stopping the antiandrogen must always be considered, as some tumours have 'learned' to be activated by these drugs. At the moment it is not yet clear if antiandrogens are of any benefit in downstaging the extent of disease before prostatectomy and/or radiotherapy. Of the currently known pure antiandrogens, bicalutamide offers some advantages over flutamide as it possesses a much longer half-life, allowing a once daily regimen, and has advantages over nilutamide in terms of fewer adverse effects.

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Clinical Trials as Topic; Cyproterone; Flutamide; Humans; Imidazoles; Imidazolidines; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds

Cyproterone (cyproterone acetate) is a steroidal antiandrogenic agent that inhibits the action of adrenal and testicular androgens on prostatic cells. Additionally, its progestogenic activity causes a centrally mediated reduction in testicular secretion of androgens. Studies have demonstrated the effectiveness of cyproterone monotherapy in patients with prostate cancer, and for those in whom orchiectomy is not an acceptable option cyproterone may be a useful alternative. In addition, the drug may be administered in combination with surgical or gonadotrophin-releasing hormone (GnRH) agonist-mediated castration to ensure ablation of adrenal androgens. However, the effectiveness of cyproterone in combination with these forms of testicular androgen deprivation remains to be fully established. Trials to date have not demonstrated prolonged survival in patients receiving the combination therapy. Importantly, however, cyproterone does prevent acute exacerbation of disease during initial treatment with a GnRH agonist. Furthermore, combination therapy tends to be associated with a lower incidence of hot flushes than GnRH agonist-mediated or surgical castration alone. Thus, cyproterone 200 mg/day has proven efficacy in preventing acute flare of disease and reducing the incidence of hot flushes associated with GnRH agonist therapy or orchiectomy. It may also facilitate maximal androgen deprivation in patients receiving GnRH agonist therapy. If this drug is used as monotherapy, dosages of 250 mg/day or greater will probably be required.

Topics: Cyproterone; Humans; Male; Prostatic Neoplasms

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.

Topics: Androgen Antagonists; Animals; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms

A case of orbital metastasis from Whitmore stage D adenocarcinoma of the prostate is described. Clinically, it presented as rapidly progressing exophthalmos of the right eye with elevation (ptosis) and abduction paralysis. The associated clinical picture of a one-year history of prostatism prompted patient referral to our department. When a patient presents with an orbital tumor and a history of cancer localized to another site, the metastatic origin of the condition should be suspected and metastasis to other sites sought. A negative finding warrants performing orbital biopsy to confirm the diagnosis. Although excision of single metastatic tumors in this site has been described, coexisting metastasis to bone and lymph nodes, the hormone dependence that these present and prostatic cancer contraindicate resection of the orbital metastatic tumor. Following bilateral orchiectomy and hormone therapy with antiandrogens micturitional symptomatology improved, tumor size was reduced, and exophthalmos disappeared. The case described herein is not the first case of this type of metastatic lesion reported in the literature; 28 cases have been reported to date. This uncommon clinical presentation with extraurological manifestations gives us an idea of the broad clinical spectrum the biological behaviour of this tumor type can adopt.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Exophthalmos; Humans; Male; Orbital Neoplasms; Orchiectomy; Palliative Care; Prostatic Neoplasms

Topics: Androgen Antagonists; Castration; Cyproterone; Estrogens; Gonadotropin-Releasing Hormone; Humans; Male; Progestins; Prostatic Neoplasms

Cyproterone acetate is a progestational antiandrogen with potent antigonadotropic activity that results in rapid suppression of serum testosterone. Used as a single agent, cyproterone acetate yields a total androgen blockade. It may be combined with low-dose diethylstilbestrol, orchiectomy, or LHRH agonists to improve, in theory, the results of such therapy. In clinical testing, cyproterone acetate has proved equivalent to diethylstilbestrol with markedly less toxicity. It is useful in conjunction with LHRH agonists, either transiently to block the flare phenomenon, or continuously to block peripheral androgen receptors; the necessity for this latter action has not yet been proved. Cyproterone acetate may afford transient objective improvement in patients not responding to other forms of hormone deprivation. Experience in this role is limited. The drug may be used to suppress the hot flushes associated with orchiectomy or LHRH agonist therapy. Cyproterone acetate induces local tumor regression; owing to its reversible effects, it is useful as neoadjuvant or adjuvant androgen withdrawal therapy in patients with lower-stage disease undergoing radical surgery or radiotherapy. Adverse effects are mostly those related to hormone withdrawal, namely, impotence, infertility, and lassitude. Gynecomastia and breast tenderness occur in less than 18% and cardiovascular complications in approximately 10% of treated men.

Topics: Androgen Antagonists; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms

Topics: Androgen Antagonists; Animals; Cyproterone; Cyproterone Acetate; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Rats; Testosterone

Endocrine-active and pure antiandrogens have different mechanisms of action and different endocrinological effects in the intact male. With pure antiandrogens as a monotherapy an elevation of plasma testosterone occurs which probably leads to the preservation of potency, the clinical significance of which in the management of prostatic carcinoma is not known. Plasma testosterone is reduced to pretreatment levels after 12 months. Longer observations are not available. In total androgen suppression regimens both types of antiandrogens have been shown in prospective trials to be at least equally effective as standard treatment. The clinical effectiveness of CPA alone in prostatic cancer has been shown to be equal to that of DES 1 mg tid. Sufficiently large prospective studies on flutamide alone in comparison to standard treatment have not been carried out. The use of antiandrogens is recommended during the initial 4 weeks of management of prostatic carcinoma patients with LH-RH agonists to prevent disease flare-up and to achieve higher early response rates in selective patients.

Topics: Androgen Antagonists; Cyproterone; Cyproterone Acetate; Flutamide; Humans; Male; Prostatic Neoplasms

Topics: Androgen Antagonists; Body Temperature Regulation; Climacteric; Clonidine; Cyproterone; Cyproterone Acetate; Estrogens; Humans; Male; Orchiectomy; Prostatic Neoplasms

Topics: Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Humans; Male; Prospective Studies; Prostatic Neoplasms; Survival Rate

Three antiandrogens are or will soon be available for clinical use. Only Flutamide has been studied in monotherapy of prostatic cancer patients. The use of Flutamide is associated with significant side effects. However, previously potent patients usually remain potent under Flutamide monotherapy. The mechanism of retained potency is poorly understood. In phase II studies parameters which are usually used for determining response of prostatic cancer to endocrine treatment react favourably to Flutamide monotherapy. Since the long-term elevation of plasma testosterone may have an impact on stimulation of prostatic cancer cells, long-term results of studies are mandatory. Such results, unfortunately, are not available in the literature. The use of "pure" antiandrogens as monotherapy and their long-term effectiveness is therefore uncertain. If effectiveness could be proven, especially in comparison to other standard forms of endocrine treatment, the use of a "pure" antiandrogen, especially of a substance with very few side effects, may provide a better quality of life than standard treatment and may therefore be preferable.

Topics: Androgen Antagonists; Anilides; Animals; Cyproterone; Cyproterone Acetate; Flutamide; Humans; Imidazoles; Imidazolidines; Male; Nitriles; Prospective Studies; Prostatic Neoplasms; Tosyl Compounds

The evolution of the ultrasonographic images of 25 patients with advanced carcinoma of the prostate receiving antiandrogen (cyproterone acetate) and LH-RH analogue therapy were studied. Thirteen patients were on daily LH-RH analogue therapy while the remaining patients received a monthly depot dose. At 6 months, the ultrasound follow-up revealed a 20.4% reduction of the transverse and a 19.8% reduction of the anteroposterior diameter for the first patient group. Similar results were observed for the second group comprised of 12 patients who received depot therapy; a mean reduction of the diameters of 119.9% and 18.7%, respectively. At 6 months, 66% of the patients in the first group and 59% of the second group showed an improvement of ultrasound patterns. Infiltration of the seminal vesicles improved for both groups, 41% and 38% of patients, respectively. However, at 12 months this rose to 50% improvement for the group on the daily treatment regimen. The follow-up data after 6 months are as yet unavailable for the group on depot therapy. Transrectal ultrasound is an easy, reproducible method that is very useful in the follow-up of patients with advanced cancer of the prostate receiving hormone therapy.

Topics: Aged; Aged, 80 and over; Carcinoma; Cyproterone; Cyproterone Acetate; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostatic Neoplasms; Ultrasonography

Topics: Androgen Antagonists; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms; Random Allocation

Topics: Androgen Antagonists; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Flutamide; Gonadotropin-Releasing Hormone; Humans; Male; Prostatic Neoplasms

Topics: Androgen Antagonists; Cyproterone; Drug Administration Schedule; Drug Therapy, Combination; Flutamide; Humans; Imidazoles; Imidazolidines; Male; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms

We present the results of a study undertaken to assess the echo patterns and prostate size in 13 patients with prostatic carcinoma treated with Lh-rh agonists. The study revealed a gradual reduction of the anteroposterior and transverse diameters. After 12 months, these were 28% and 22% of their respective initial values. Furthermore, the prostatic echo patterns changed significantly in 66% of the patients, and infiltration of the seminal vesicle improved or became stable in 50%. These findings suggest that transrectal ultrasonography may be useful in the follow up of prostatic carcinoma patients receiving hormone therapy.

Topics: Aged; Aged, 80 and over; Cyproterone; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostate; Prostatic Neoplasms; Ultrasonography

Antiandrogens, substances that prevent androgens from expressing their activity at target cells, play an important role in the treatment of prostate cancer. The most frequently used substances have either a steroidal structure (cyproterone acetate) or a non-steroidal structure (Flutamide or Anandron). Antiandrogens have been tested both alone and in combination with treatments aimed at inhibiting testicular secretion (castration, LH-RH analogs), thereby producing complete blockade of androgen secretion and action. Patients treated by such combination protocols have often shown an improvement in the percentage of remissions and, less often, improvement in survival. Administration of antiandrogens improves the clinical symptoms of patients with benign prostatic hypertrophy, but the exact mechanism of their action requires further investigation. Cutaneous manifestations due to hyperandrogenicity (hirsutism, alopecia, acne) have also been improved by cyproterone acetate, which is often given together with estrogens (reversed sequential regime), by spironolactone or topically applied products. Finally, antiandrogens have been successfully used to treat breast cancer in men, early puberty, hypersexuality and sexual deviations.

Topics: Androgen Antagonists; Breast Neoplasms; Cyproterone; Cyproterone Acetate; Female; Flutamide; Humans; Imidazoles; Imidazolidines; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Puberty, Precocious; Skin Diseases; Spironolactone

The various clinical trials suggest that the qualitative and quantitative responses of patients with Stage D prostatic carcinoma to antiandrogens are similar to those achieved with conventional endocrine therapy. These antiandrogens appear generally safe and many avoid the increased risks of cardiovascular or thromboembolic complications seen with estrogen therapy. Further, flutamide appears to have a lesser adverse effect on libido and sexual potency than do alternative therapies. Antiandrogens offer an alternative mode of therapy for previously untreated patients with advanced prostatic cancer but have produced no convincing benefits in hormonally refractory patients.

Topics: Androgen Antagonists; Androgens; Anilides; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Flutamide; Humans; Male; Megestrol; Megestrol Acetate; Prostatic Neoplasms

Topics: Androgen Antagonists; Animals; Cyproterone; Cyproterone Acetate; Female; Flutamide; Glucuronidase; Gonadotropin-Releasing Hormone; Guinea Pigs; Kidney; Male; Mice; Prostatic Neoplasms; Rats; Sex Differentiation; Time Factors

Topics: Antineoplastic Combined Chemotherapy Protocols; Castration; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Prostatic Neoplasms

Many treatment modalities are available to patients with disseminated adenocarcinoma of the prostate. Although no single therapeutic approach can be advocated for all patients at the present time, delay of endocrine manipulation until the onset of symptoms is the recommended approach because it maintains the most normal lifestyle in these patients. With the onset of symptoms such as bone pain or urinary retention, or perhaps as disease progression becomes apparent, orchiectomy is recommended to patients with increased cardiovascular risks as well as to those patients who are judged irresponsible in taking oral estrogens. A dose of 1 mg of diethylstilbestrol three times daily achieves a castrate level of serum testosterone and may not increase cardiovascular mortality. Because of the relative safety and lack of side effects, GnRH analogues represent an alternative treatment in selected patients, particularly in those who refuse orchiectomy or have an increased risk of developing cardiovascular complications. Hormonal manipulation with androgen deprivation remains the cornerstone of treatment and provides clinical remission in the majority of patients with advanced prostate cancer. The prognosis is poor once tumor has recurred. Several secondary forms of endocrine therapy are available, but it would help to be able to select those patients with hormonally sensitive tumors that would respond favorably to these modalities. Transurethral surgery and radiotherapy are effective in palliating patients with bladder outlet obstruction and bony metastases unresponsive to hormonal therapy. Nonhormonal cytotoxic agents are available, but well-controlled studies are required to determine the value of specific agents, whether used alone or in combination.

Topics: Adrenalectomy; Aminoglutethimide; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Estrogens; Flutamide; Glucocorticoids; Humans; Ketoconazole; Male; Megestrol; Megestrol Acetate; Orchiectomy; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms; Spironolactone; Time Factors

The effectiveness of aminoglutethimide as an adrenal inhibitor has been well-documented by decreases in plasma testosterone and delta 4 levels, which fall significantly following the drug in previously orchiectomized patients. The use of cortisone or cortisol along with aminoglutethimide complicates the interpretation of the role of aminoglutethimide in effecting clinical responses. However, since physiologic replacement doses were used in most cases, a significant role for cortisone in effecting a clinical response is unlikely. Aminoglutethimide does have side-effects including rash and lethargy. It requires administration of replacement doses of cortisone and sometimes mineralocorticoid as well since it inhibits adrenal steroid synthesis in all pathways. Peripheral adrenal androgen inhibitors, such as flutamide, Megace, cyproterone acetate or 5 alpha-reductase inhibitors, in the future may be equally effective and simpler to administer than aminoglutethimide but objective and adequate numbers of studies using acceptable objective criteria must be done in order to adequately compare these drugs to aminoglutethimide. There appears to be approximately a 33% response rate (partial objective regression and objectively stable) following blockade of adrenal androgens in patients in relapse after castration. Blockade of adrenal androgen is certainly more tolerable and has many fewer side-effects than the alternative of chemotherapy which does not give response rates in most cases that are significantly different from those noted with aminoglutethimide. Murray's paper, combined with prior studies by Drago et al., goes a long way in establishing adrenal androgen blockade with that drug as the next step to be taken in patients following relapse from prior castration (medical or surgical). The most important question revolves around the timing of adrenal androgen blockade. As stated by Murray, will adrenal androgen blockade provide better survival if given earlier following relapse? The answer is not known yet. The answer may come from the work of Labrie [1], Geller and Albert [2] and others, who suggest that total survival in prostate cancer may be improved with blockade of adrenal androgens not after relapse following castration, but with panandrogen blockade at the time of initial therapy for prostate cancer.

Topics: Adrenalectomy; Aminoglutethimide; Androgen Antagonists; Castration; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Dehydroepiandrosterone; Dihydrotestosterone; Humans; Male; Megestrol; Megestrol Acetate; Neoplasm Metastasis; Prognosis; Prostate; Prostatic Neoplasms

Topics: Adrenalectomy; Castration; Cyproterone; Diethylstilbestrol; Hormones; Humans; Hypophysectomy; Ketoconazole; Male; Middle Aged; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms; Receptors, Cell Surface; Tamoxifen; Testosterone

Topics: Androgen Antagonists; Animals; Buserelin; Cyproterone; Cyproterone Acetate; Dogs; Drug Therapy, Combination; Flutamide; Humans; Male; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms; Rats; Receptors, Cell Surface; Receptors, LHRH

Topics: Aminoglutethimide; Androgen Antagonists; Cyproterone; Cyproterone Acetate; Estrogen Antagonists; Flutamide; Hormones; Humans; Male; Pituitary Hormone-Releasing Hormones; Prolactin; Prostatic Neoplasms

Topics: Acid Phosphatase; Antineoplastic Agents; Bromocriptine; Castration; Combined Modality Therapy; Cyproterone; Estramustine; Estrogens; Fluorouracil; Humans; Lisuride; Male; Neoplasm Metastasis; Prostatic Neoplasms; Random Allocation

Topics: Cyproterone; Diethylstilbestrol; Estrogens; Humans; Male; Medroxyprogesterone; Prostatic Neoplasms

The ongoing development and gradual availability of the new anti-androgens hold exciting clinical implications for the future. The biosynthesis and interchangeability of the sex steroids, the roles of the ovaries and adrenals and the value and interpretation of biochemical assays in clinical practice are briefly discussed. Because the anti-androgens are used primarily for seborrhoea/acne/hirsutism/oligomenorrhoea, the pathophysiological basis of this socially debilitating syndrome is discussed. The classification of the anti-androgens, their indications, side-effects, dosage schemes and results of treatment are reviewed. Finally, a summary of a possible clinical management regimen is presented.

Topics: 17-Ketosteroids; Acne Vulgaris; Adrenal Hyperplasia, Congenital; Androgen Antagonists; Androgens; Androsterone; Contraceptives, Oral, Hormonal; Cyclopentanes; Cyproterone; Dermatitis, Seborrheic; Dihydrotestosterone; Estradiol Congeners; Female; Follicle Stimulating Hormone; Glucocorticoids; Hirsutism; Humans; Hydroxysteroids; Luteinizing Hormone; Male; Medroxyprogesterone; Nandrolone; Prostatic Neoplasms; Receptors, Androgen; Sex Hormone-Binding Globulin; Steroids; Testosterone

Topics: Acne Vulgaris; Alopecia; Animals; Bone Development; Cyproterone; Female; Fertility; Hirsutism; Humans; Libido; Male; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Puberty; Sebaceous Glands; Seminal Vesicles; Sex Differentiation; Skin; Testis

Topics: Biopsy; Castration; Cryosurgery; Cyproterone; Estrogens; Humans; Hypophysectomy; Male; Neoplasm Metastasis; Prostatic Neoplasms

Many antiandrogens, mainly steroidal and some nonsteroidal agents, have been synthesized and tested in several available biological assays. Unfortunately, many of these compounds have other biological activities which make it difficult to ascertain the precise mechanism of antiandrogenic action. The blocking of androgen action can be accomplished by a number of ways: (1) the inhibition of gonadotropin release and/or synthesis, (2) the interference with testosterone and/or dihydrotestosterone biosynthesis, (3) the blocking of protein synthesis, and (4) the competition with androgens at receptor sites. Although the major reason for the development of antiandrogens is to utilize them in certain clinical situations, some have become important tools in studying androgen action, particularly on the molecular level. The clinical effectiveness of some antiandrogens in prostatic hyperplasias, hirsutism, and acne represents an important advance in therapeutics, but the search for more potent antiandrogens with minimal side effects should continue.

Topics: Acne Vulgaris; Androgen Antagonists; Animals; Biological Assay; Comb and Wattles; Cyproterone; Female; Fertility; Flutamide; Genitalia, Male; Hirsutism; Male; Phthalimides; Progesterone; Prostatic Hyperplasia; Prostatic Neoplasms; Sebaceous Glands; Sebum; Sex Differentiation; Sexual Behavior, Animal; Sexual Dysfunction, Physiological; Steroids

Accurate diagnosis and staging of carcinoma of the prostate is essential to rational management of this disease. Once dissemination outside the periprostatic area is established, treatment is essentially limited to systemic efforts to control or suppress tumor growth and local efforts to minimize secondary effects of tumor deposits. Disseminated tumor limited to pelvic nodes constitute a possible exception to this statement since excisional and radiotherapeutic efforts to eradicate these foci may be successful. At the present time, changes in a number of objective and subjective parameters are utilized to assess the effect of therapeutic endeavors. When these are taken as a group and combined with a clinical judgement, they undoubtedly have merit. On the other hand, when utilized in a relative fashion as isolated indicators of tumor responsiveness or recurrence, their value is limited. Since most patients with disseminated carcinoma of the prostate die from their disease, critical analysis of survival data is at present likely to provide the most accurate assessment of a therapeutic endeavor. Estrogen administration or orchiectomy seem to be the systemic measures which combine relatively limited risk of morbidity with the greatest hope of initially controlling disseminated carcinoma of the prostate. Of these, evidence suggests that low dose estrogen therapy, 1 mg stilbestrol daily, provides the best opportunity for long-term control. Although length of survival does not seem to depend on the time at which the therapy is instituted, our prejudice is usually to start treatment when dissemination is recognized. The hope of providing a longer period of a better life by this practice requires evaluation. Combining local measures such as transurethral resection with systemic measures may add to patient comfort and longevity. Recurrent progression of tumor after initial hormonal measures in often difficult to recognize and accept. In patients with recurrent tumor activity, measures based on the concept of persistence of hormone dependence have produced disappointing results. More sophisticated selection techniques may identify a small group of patients in whom this approach is likely to produce desirable changes. For the most part chemotherapeutic agents hold greater promise of effective therapy in this group of patients.

Topics: Antineoplastic Agents; Body Fluids; Castration; Cyproterone; Diethylstilbestrol; Estrogens; Humans; Hypophysectomy; Immunotherapy; Male; Neoplasm Metastasis; Prostatectomy; Prostatic Neoplasms; Testosterone

Until the last few years very little information has been available regarding the potential of chemotherapy in prostatic cancer. Few drugs have been adequately tested to determine their efficacy, if any. Of the little conventional chemotherapy that has been documented, only diethylstilbestrol diphosphate (Stilphostrol, Honvan) has been safe, effective (at least in relieving bone pain) and available for repeat courses of treatment. The several well controlled clinical trials recently embarked upon and described in this article should reveal much about the effectiveness in prostatic cancer of agents already accepted in chemotherapy of other malignancies. Newer drugs will also require thorough testing. At this time no specific recommendations for chemotherpay other than the use of intravenous diethylstillbestrol diphospate can be made. Agents like estramustine phosphate (Estracyt) and flutamide (SCH-13521) with little to no bone marrow, liver, or renal toxicity are very promising. Studies of single-agent, sequential, and combined chemotherapy will necessarily lead to safe effective chemotherapy as adjuncts to surgery and/or radiotherapy for prostatic cancer in all stages.

Topics: Aged; Alkylating Agents; Antibiotics, Antineoplastic; Antimetabolites; Antineoplastic Agents; Bromocriptine; Cyproterone; Depression, Chemical; Diethylstilbestrol; Drug Therapy, Combination; Estramustine; Fluorouracil; Flutamide; Health Facilities; Hematologic Diseases; Humans; Kinetics; Male; Mitosis; Nitrogen Mustard Compounds; Prostatic Neoplasms

Topics: Carcinoma; Cyproterone; Female; Hirsutism; Humans; Male; Paraphilic Disorders; Prostatic Hyperplasia; Prostatic Neoplasms; Puberty, Precocious; Sex Offenses

Topics: Adenocarcinoma; Age Factors; Aged; Cyclophosphamide; Cyproterone; Diethylstilbestrol; Fluorouracil; Humans; Male; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prognosis; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Urination

Topics: Acne Vulgaris; Alopecia; Androgen Antagonists; Bone Development; Cyproterone; Female; Growth; Hirsutism; Humans; Hypertrichosis; Libido; Male; Prostate; Prostatic Neoplasms; Puberty, Precocious; Seminal Vesicles; Sexual Dysfunction, Physiological; Skin

Topics: Adenocarcinoma; Biopsy; Cyproterone; Diethylstilbestrol; Estrogens; Humans; Hypophysectomy; Lymphatic Metastasis; Male; Neoplasm Metastasis; Prostate; Prostatic Neoplasms

Topics: Androgen Antagonists; Animals; Body Height; Bone Development; Cell Differentiation; Contraceptives, Oral; Cyproterone; Epididymis; Female; Gonads; Hirsutism; Humans; Libido; Male; Pregnadienes; Pregnancy; Prostate; Prostatic Neoplasms; Puberty, Precocious; Sebaceous Glands; Seminal Vesicles; Sexual Dysfunction, Physiological; Testosterone

Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin. After an initial 3-6 month period of androgen suppression, 126 men were randomised and treated with radiotherapy using a 2 by 2 factorial trial design. The initial radiotherapy tumour target volume included the prostate and base of seminal vesicles (SV) or complete SV depending on SV involvement risk. Treatments were randomised to deliver a dose of 64 Gy with either a 1.0 or 1.5 cm margin around the tumour volume (1.0 and 1.5 cm margin groups) and also to treat either with or without a 10 Gy boost to the prostate alone with no additional margin (64 and 74 Gy groups). Tumour control was monitored by prostate-specific antigen (PSA) testing and clinical examination with additional tests as appropriate. Acute and late side effects of treatment were measured using the Radiation Treatment and Oncology Groups (RTOG) and LENT SOM systems. The results showed that freedom from PSA failure was higher in the 74 Gy group compared to the 64 Gy group, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71% (95% CI 58-81%) in the 74 Gy group vs 59% (95% CI 45-70%) in the 64 Gy group. There were 23 failures in the 74 Gy group and 33 in the 64 Gy group (Hazard ratio 0.64, 95% CI 0.38-1.10, P=0.10). No difference in disease control was seen between the 1.0 and 1.5 cm margin groups (5-year actuarial control rates 67%, 95% CI 53-77% vs 63%, 95% CI 50-74%) with 28 events in each group (Hazard ratio 0.97, 95% CI 0.50-1.86, P=0.94). Acute side effects were generally mild and 18 weeks after treatment, only four and five of the 126 men had persistent > or =Grade 1 bowel or bladder side effects, respectively. Statistically significant increases in acute bladder side effects were seen after treatment in the men receiving 74 Gy (P=0.006), and increases in both acute bowel side effects during treatment (P=0.05) and acute bladder sequelae (P=0.002) were recorded for men in the 1.5 cm margin group. While statistically significant, these differences were of short duration and of doubtful clinical importance. Late bowel side effects (RTOG> or =2) were seen more commonl

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Cyproterone; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Pilot Projects; Prostate-Specific Antigen; Prostatic Neoplasms; Radiation Injuries; Radiotherapy Dosage; Radiotherapy, Conformal; Rectum; Treatment Outcome; Urinary Bladder

This paper reports on results of the EORTC protocol 30892, an open, prospective, randomized study of 310 patients with previously untreated metastatic prostate cancer with favourable prognostic factors who were treated by either flutamide (FLU) or cyproterone acetate (CPA) monotherapy. The final analysis with regard to the main end points, time to progression and survival are still pending. Final results related to the evaluation of sexual functioning prior to and under treatment are reported here. Of 310 randomized patients 294 were eligible for evaluation within this side study. The median age was 71 years (range 48-85). Potential risk factors related to age, general health and prostate cancer were evaluated. For evaluation of sexual functions a five-item questionnaire was used which was administered by the investigator. The protocol allowed time dependent observations at 3-monthly follow-up visits. Sexual functioning was dependent on age but not on prostate cancer-related parameters. Sexual functions at entry were similar within the two treatment groups, spontaneous (nightly) erections and sexual activity were seen in 43-51% and 29-35% of cases. Under treatment, sexual functions under FLU and CPA declined slowly with median times of 12.9 and 5.8 months versus 13.7 and 8.9 months respectively for spontaneous erections and sexual activity. Eventually, with an average observation time in excess of 2 years, loss of spontaneous erections and of sexual activity occurred in 80% versus 92% and in 78% versus 88% of men under FLU versus CPA treatment respectively. None of these differences reached statistical significance. Maintenance of potency under treatment with FLU as reported in the literature is not confirmed in this study. However, loss of sexual functions under monotherapy with both antiandrogens is slow and 10-20% of men retain sexual activity after 2-6 years of treatment. This observation can be exploited in new treatment schemes and is likely to lead to improved quality of life. The advantage of FLU in time and total preservation of sexual functions is statistically not significant and must be balanced against the side effects of FLU and other pure antiandrogens, which may exceed those of CPA especially with respect to gynaecomastia. Hepatic toxicity may limit the long-term use of both drugs.

Topics: Aged; Androgen Antagonists; Cyproterone; Erectile Dysfunction; Flutamide; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Quality of Life; Sexuality

During a 2-year period, 37 patients with symptomatic metastatic prostatic cancer were included in a prospective randomized phase-III trial. Nineteen patients were randomized to subcapsular orchiectomy, and 18 to cyproterone acetate (CPA) treatment with a dose of 50 mg b.i.d. The median age of the patients was 74 years (range 48-88 years), with no differences between the treatment groups. At 3, 6, and 12 months after initiation of the therapy and then every 6 months, patients were clinically and biochemically examined, and isotope scans and X-rays were performed. All patients were followed until death. Relief from symptoms was found following 3 months of treatment in 70.6% (95% confidence limits = 44.0-89.7%) of the patients treated with CPA, and in 83.3% (95% confidence limits = 58.6-96.4%) of the orchiectomized patients. The median time to relapse was 9 months in the CPA group, and 11 months in the orchiectomy group (p greater than 0.05). The median survival time was 13 months, with no differences between the groups. The treatment of advanced prostatic cancer with CPA is found to be a valuable alternative to orchiectomy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Cyproterone; Cyproterone Acetate; Humans; Male; Middle Aged; Orchiectomy; Palliative Care; Prospective Studies; Prostatic Neoplasms

Sixty new patients with advanced local or metastatic prostatic cancer were randomised to receive either bilateral orchiectomy, orchiectomy plus dexamethasone 0.5 mg in the morning and 0.3 mg at night, or orchiectomy plus cyproterone acetate 100 mg 3 times per day. All surviving patients have been followed up for a minimum of 2 years. An improvement in both objective and subjective responses in patients receiving dexamethasone compared with those receiving cyproterone acetate suggests a possible additional role for the pituitary in the control of prostatic tumour growth. A larger study with longer follow-up may be indicated.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Androstenedione; Cyproterone; Cyproterone Acetate; Dexamethasone; Humans; Hydrocortisone; Luteinizing Hormone; Male; Middle Aged; Orchiectomy; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Testosterone

The aim of the present investigation was to establish whether in advanced prostatic carcinoma in relapse treated with LHRH analogues combined with cyproterone acetate (CPA), substitution of this antiandrogen with another compound such as flutamide (FLU) might lead to further subjective and objective improvement. The present randomized study was carried out on 100 patients in relapse treated with long acting LHRH analogue + CPA: 52 patients were submitted to combination therapy with FLU, whilst the remaining 48 cases continued with CPA treatment. Plasma levels of gonadotropin FSH-LH, androstenedione and dehydroepiandrosterone sulphate were significantly reduced by both treatments, testosterone fell to castration values, but prolactin showed no change. Progress of the disease was confirmed in all the patients who continued with CPA treatment with a median survival rate of 9.3 +/- 2 months from the start of the second cycle of CPA. In the FLU-treated group, the overall objective response differed significantly in relation to the stage of the disease. In fact, in stage D2, the response was poor with a median survival of 12 +/- 2 months, which is almost comparable to that in the CPA group. In stage D1, a clinical improvement, even if of short duration, was observed in almost 50% of the cases with a median survival of 18 +/- 3 months. Good results were also obtained in undifferentiated tumours, FLU probably acting as an antimitotic agent. Moreover, FLU also exerted an analgesic effect, with relief of bone pain in 65% of the cases in stage D2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Androgen Antagonists; Anilides; Buserelin; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Random Allocation

Antiandrogens, preventing androgen action at target tissue level, are used in the treatment of various androgen-dependent diseases. Pharmacologically these substances have either a steroidal structure, like cyproterone acetate (CPA) and spironolactone (SPL), or a non-steroidal structure, like flutamide (FLU). In women with hyperandrogenism (PCO syndrome, idiopathic hirsutism, acne), clinical benefit may be obtained with CPA, which also displays a progestational activity and an antigonadotropic effect. CPA (25-50 mg/day) is used in combination with ethinyl-estradiol (EE) (20-30 micrograms/day) in reversed sequential regimen. SPL, less effective than CPA may be employed in moderate hirsutism and acne at dosages of 100-200 mg/day. During SPL treatment menstrual irregularities are frequent: in this case an association with oral contraceptives is indicated. SPL + bromocriptine (2.5-5 mg/day) has been experienced with success in PCO syndrome. The pure antiandrogen FLU, inducing progressive increase in LH and testosterone secretion, may be used only in combination with oral contraceptives. In men antiandrogens have been tested in BPH and prostatic carcinoma. In BPH the decrease in nuclear receptors and DHT nuclear content during CPA or FLU may represent the rational base of the medical treatment. An improvement in urinary obstructive manifestation has been observed with CPA alone or associated with tamoxifen (100 mg + 100 mg day). In advanced prostatic carcinoma antiandrogens represent a good alternative to estrogen therapy with less side effects and in combination with surgical or medical castration (LH-RH analogues) achieve a complete androgen blockade. An increase in the percentage of remissions and survival has been reported.

Topics: Acne Vulgaris; Adult; Androgen Antagonists; Cyproterone; Cyproterone Acetate; Dermatitis, Seborrheic; Female; Flutamide; Hirsutism; Humans; Male; Prostatic Neoplasms; Spironolactone

Topics: Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Humans; Male; Prospective Studies; Prostatic Neoplasms; Survival Rate

Three antiandrogens are or will soon be available for clinical use. Only Flutamide has been studied in monotherapy of prostatic cancer patients. The use of Flutamide is associated with significant side effects. However, previously potent patients usually remain potent under Flutamide monotherapy. The mechanism of retained potency is poorly understood. In phase II studies parameters which are usually used for determining response of prostatic cancer to endocrine treatment react favourably to Flutamide monotherapy. Since the long-term elevation of plasma testosterone may have an impact on stimulation of prostatic cancer cells, long-term results of studies are mandatory. Such results, unfortunately, are not available in the literature. The use of "pure" antiandrogens as monotherapy and their long-term effectiveness is therefore uncertain. If effectiveness could be proven, especially in comparison to other standard forms of endocrine treatment, the use of a "pure" antiandrogen, especially of a substance with very few side effects, may provide a better quality of life than standard treatment and may therefore be preferable.

Topics: Androgen Antagonists; Anilides; Animals; Cyproterone; Cyproterone Acetate; Flutamide; Humans; Imidazoles; Imidazolidines; Male; Nitriles; Prospective Studies; Prostatic Neoplasms; Tosyl Compounds

This prospective randomized phase III trial compares orchidectomy as standard androgen-deprivative therapy of advanced (metastatic) prostatic cancer with treatment using the LHRH agonist Buserelin administered as nasal spray 3 daily doses of 400 micrograms, and combined with cyproterone acetate (CPA) 3 daily doses of 50 mg orally for 2 weeks initially to prevent flare-up of the disease, or continuously as complete androgen blockade. The trial was closed to entry in September 1989 when 367 patients were recruited. Patients were stratified for performance status (WHO) and metastatic status prior to randomization. According to patient and disease characteristics spreading of patients over the 3 arms was without statistical significant differences. Ineligibility was 5 and 4% of the patients were only partly evaluable. In March 1990 a first, preliminary analysis was performed. At that time 207 patients were off-study for progression or death and median follow-up was 1 yr. As to time-to-progression and survival there were no significant differences between the 3 arms. The meaning of this in regard to results of other trials with complete androgen blockade is discussed.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Cyproterone; Cyproterone Acetate; Europe; Humans; Male; Middle Aged; Orchiectomy; Prospective Studies; Prostatic Neoplasms; Risk Factors

This report is a retrospective clinical randomized study carried out on 114 cases of incidental prostatic carcinoma aged 55-87 years, 58 untreated and 56 treated with cyproterone acetate (CPA 200 mg/day) for 6 months, immediately after surgery. 78 cases were staged A1 and the remaining 36 A2. In stage A1, 75 cases were histologically graded G1, and 3 G2, whereas in stage A2, 7 cases were G1, 19 G2 and 10 G3. Moreover, flow cytometric DNA analysis showed in A1 20 G1 carcinomas with nuclear diploidy and 3 G2 with nuclear aneuploidy, in stage A2, 4 G3 tumors with nuclear aneuploidy. During the 4-year follow-up, 25/28 patients of the untreated group and 15/56 of the CPA-treated group were found in progression. In A1, progression was found in 6/37 untreated patients and 5/41 CPA-treated, whilst in A2 progression was observed in 19/21 untreated patients and in 10/15 treated with CPA. The critical period for progression was between the 2nd and 3rd year of follow-up. In A1, therefore, 6 months of therapy with CPA does not modify the progression rate, which is significantly improved in A2 (66% in the treated and 90% in the untreated group) during the first 30 months of follow-up. The prognosis may probably be further improved by continuing endocrine therapy.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; DNA, Neoplasm; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Retrospective Studies

Topics: Androgen Antagonists; Breast; Buserelin; Cardiovascular Diseases; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Goserelin; Humans; Male; Prospective Studies; Prostatic Neoplasms

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)

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms; Testosterone

The European Organization for Research on Treatment of Cancer Genitourinary Group performed a multivariate statistical analysis of prognostic factors based on 436 patients entered between 1976 and 1981 in 2 randomized prospective trials that compared 4 different hormonal treatment regimens. Only previously untreated patients with advanced (stage T3/T4/M0 or M1) prostatic cancer were eligible. After identification of prognostic factors by means of univariate analyses a multivariate analysis using Cox's proportional hazards regression model was done. This test identified performance status (according to the Eastern Cooperative Oncology Group scale) as the most important factor, followed by acid phosphatase (more than 2 times normal) for stage M0 cancer patients, and alkaline phosphatase, T category and the presence or absence of associated chronic disease for stage M1 cancer patients. Based on these 4 variables nonbedridden patients with metastatic disease can be divided into 2 groups: poor and good risk patients, with median survivals of 1 and 3 years, respectively. This study shows that routine clinical and laboratory data already provide an excellent indication as to the prognosis.

Topics: Adult; Aged; Aged, 80 and over; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Europe; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Multicenter Studies as Topic; Nitrogen Mustard Compounds; Prognosis; Prospective Studies; Prostatic Neoplasms; Random Allocation; Statistics as Topic

Topics: Androgen Antagonists; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms; Random Allocation

Topics: Androgen Antagonists; Antineoplastic Agents; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Europe; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Multicenter Studies as Topic; Prostatic Neoplasms; Random Allocation

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Buserelin; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Delayed-Action Preparations; Flutamide; Humans; Male; Middle Aged; Prostatic Neoplasms; Random Allocation

Tumor flare is reported in up to 40% of patients treated with gonadotrophin-releasing hormone analogues for prostate cancer. In order to investigate the optimal way to eliminate tumor flare, we have treated patients with one of three different antiandrogen regimens used in combination with gonadotrophin-releasing hormone (GnRH) agonist. The early results of this study are presented here. Thirty patients with advanced symptomatic disease were randomized to receive either cyproterone acetate 50 or 100 mg three times daily or flutamide 250 mg three times daily given for 1 week before and during the first month of GnRH agonist treatment. The endocrine profiles of these patients were compared with those of historic controls treated with depot agonist alone. Three patients treated with low-dose cyproterone acetate and one with flutamide developed a transient exacerbation of their disease. No patients treated with the higher-dose cyproterone acetate regimen developed tumor flare. No patients treated with cyproterone acetate had an increase in serum testosterone above baseline following depot GnRH agonist implantation. All patients treated with flutamide had increases in serum testosterone, but this did not significantly increase further with implantation. This study suggests that all patients receiving GnRH agonist treatment should be pretreated with cyproterone acetate 100 mg three times daily for 1 week before implantation and for the first treatment month.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Cyproterone; Cyproterone Acetate; Delayed-Action Preparations; Flutamide; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Phosphoric Monoester Hydrolases; Prostatic Neoplasms; Random Allocation; Testosterone

Topics: Adenocarcinoma; Clinical Protocols; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Europe; Humans; Male; Orchiectomy; Prostatic Neoplasms

Topics: Antineoplastic Agents; Carcinoma; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Drug Administration Schedule; Estramustine; Europe; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Prostatic Neoplasms; Random Allocation

From June 1, 1981 to December 31, 1985, 122 patients aged 54 to 83 years, with locally advanced prostatic carcinoma, were treated with buserelin. Nineteen of the patients received combined therapy with buserelin and androcur for the first 3 months. To control the response of the primary tumor to therapy, fine-needle aspiration biopsy of the prostate was made in all patients at 3-month intervals. Fifty-eight (76.3%) of 76 patients with locally advanced prostatic carcinoma, with or without bone metastases, who underwent buserelin therapy for periods of 12-54 months showed good to satisfactory regression grades in the primary tumor. Eighteen patients (23.7%) showed poor regression or none, established by cytological findings and the measure of DNA by means of single cell-scanning cytophotometry. In three of the 58 patients, tumor progression or bone metastases occurred despite favorable regression grade; these were the only cases in which there was a discrepancy between the clinical course of the disease and the grade of regression in the primary tumor. According to TNM classification, 68 of the 78 patients treated for 12-54 months were in stage T3 NX M0; eight were in stage T3/T4 NX M1. On the basis of our long-term studies, it can be stated that buserelin therapy induces positive therapy response in more than 75% of locally advanced, inoperable, primary prostatic carcinoma. The clinical castration caused by buserelin through selective suppression of gonadotrophic secretion in the pituitary gland is, as the term implies, no more effective than surgical castration. However, the gonadotrophin suppression induced by buserelin is reversible and spares the patient the psychic stress of orchiectomy. This is a decisive advantage in light of the fact that in 20-40% of patients with locally advanced primary prostatic carcinoma, the primary tumor is hormone-refractory, and surgical castration would prove unnecessary after all.

Topics: Aged; Aged, 80 and over; Biopsy, Needle; Buserelin; Carcinoma; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Cytophotometry; DNA, Neoplasm; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Neoplasm Staging; Prostate; Prostatic Neoplasms; Remission Induction

Superactive analogues of luteinizing hormone-releasing hormone (LHRH) have now widely been used in the management of metastatic prostate cancer. In a multicentric study, we have studied the effectiveness of buserelin in patients with previously untreated histologically confirmed metastatic prostate cancer. Fifty-eight patients were enrolled in the study and are now followed for at least 12 months. The treatment consisted of 500 micrograms buserelin administered subcutaneously (s.c.) 3 times daily for the first seven days and thereafter a thrice-daily dose of 400 micrograms buserelin administered intranasally (i.n.). A continuous reduction of testosterone to castrate levels could be obtained in all patients. The following objective responses were seen during the 12 months study period: 5 patients (8.6%) achieved complete regression after 3-10 months (mean 6.4 m); 24 patients (41.4%) achieved partial regression after 1-12 months (mean 4.5 m); 7 patients (12%) remained stable throughout the study; 22 patients (32.3%) developed progression after 2-12 months (mean 7.2 m). Toxicity was minimal. Only one patient dropped out of the study because of side effects. These results are comparable with results of other forms of hormonal treatment of prostate cancer. Long-term results of 3 EORTC GU group comparative studies in metastatic prostate cancer are now available. The first study, 30761, compared cyproterone acetate, medroxy-progesterone acetate, and DES. No differences between the 3 treatment arms were observed except for medroxy-progesterone acetate, which showed less therapeutic effect in the dosage used. Protocol 30762 compared DES and estramustine phosphate. No significant difference in objective response and survival was noted. Protocol 30805 studied a comparison between orchiectomy alone and orchiectomy supplemented by cyproterone acetate and DES. Again no statistically significant difference was found between the three therapeutic arms.

Topics: Aged; Buserelin; Clinical Trials as Topic; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Humans; Lymphatic Metastasis; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Netherlands; Orchiectomy; Prostatic Neoplasms; Remission Induction; Time Factors

Topics: Antineoplastic Combined Chemotherapy Protocols; Castration; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Prostatic Neoplasms

Topics: Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Heart; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Prostatic Neoplasms

The theoretical basis of 'total androgen blockade' in the treatment of advanced prostatic cancer is reviewed. The results of experimental and clinical data in the literature comparing medical or surgical castration alone versus castration plus peripheral antiandrogens are discussed. Most of these studies could not reproduce Labrie's results and do not establish the benefit of total androgen blockade. The author produces his own experience with LHRH analogs alone (Depot Zoladex; 30 patients) compared to orchidectomy plus antiandrogens (17 patients). After 2 years, there is no difference in the progression and death rates between the two groups. Moreover, the administration of an antiandrogen in 15 patients relapsing after first-line hormonal treatment (Zoladex or orchidectomy) produced an objective response in only 2 of them. 9 patients experienced a subjective response but the duration of response was very short (medium 3 months).

Topics: Androgen Antagonists; Buserelin; Cyproterone; Cyproterone Acetate; Flutamide; Goserelin; Humans; Male; Multicenter Studies as Topic; Orchiectomy; Prostatic Neoplasms; Time Factors

Many treatment modalities are available to patients with disseminated adenocarcinoma of the prostate. Although no single therapeutic approach can be advocated for all patients at the present time, delay of endocrine manipulation until the onset of symptoms is the recommended approach because it maintains the most normal lifestyle in these patients. With the onset of symptoms such as bone pain or urinary retention, or perhaps as disease progression becomes apparent, orchiectomy is recommended to patients with increased cardiovascular risks as well as to those patients who are judged irresponsible in taking oral estrogens. A dose of 1 mg of diethylstilbestrol three times daily achieves a castrate level of serum testosterone and may not increase cardiovascular mortality. Because of the relative safety and lack of side effects, GnRH analogues represent an alternative treatment in selected patients, particularly in those who refuse orchiectomy or have an increased risk of developing cardiovascular complications. Hormonal manipulation with androgen deprivation remains the cornerstone of treatment and provides clinical remission in the majority of patients with advanced prostate cancer. The prognosis is poor once tumor has recurred. Several secondary forms of endocrine therapy are available, but it would help to be able to select those patients with hormonally sensitive tumors that would respond favorably to these modalities. Transurethral surgery and radiotherapy are effective in palliating patients with bladder outlet obstruction and bony metastases unresponsive to hormonal therapy. Nonhormonal cytotoxic agents are available, but well-controlled studies are required to determine the value of specific agents, whether used alone or in combination.

Topics: Adrenalectomy; Aminoglutethimide; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Estrogens; Flutamide; Glucocorticoids; Humans; Ketoconazole; Male; Megestrol; Megestrol Acetate; Orchiectomy; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms; Spironolactone; Time Factors

Topics: Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms; Random Allocation

Topics: Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Prostatic Neoplasms

Topics: Clinical Trials as Topic; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Humans; Male; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms

Two randomized trials were started in 1976 by the European Organization for Research on Treatment of Cancer urological group. Trial 30761 compared 1 mg. diethylstilbestrol orally 3 times daily to 250 mg. oral cyproterone acetate daily and to 500 mg. medroxyprogesterone acetate intramuscularly 3 times weekly for 8 weeks, then 200 mg. orally daily. Trial 30762 compared 3 mg. diethylstilbestrol to 560 mg. estramustine phosphate orally for 8 weeks and then 280 mg. daily. The 239 patients in study 30761 and 226 in study 30762 were evaluated for cardiovascular toxicity during treatment. Various types of side effects (fluid retention, hypertension, electrocardiographic changes, myocardial infarction and thromboembolic disease) and their degrees of severity were analyzed. In both studies the most frequent type of cardiovascular toxicity was represented by fluid retention. Cardiovascular toxicity as a whole was higher with diethylstilbestrol than with estramustine phosphate or medroxyprogesterone acetate therapy, and was the lowest with cyproterone acetate therapy. The risk of severe cardiovascular complications developing was the highest during the first 6 months of treatment. Increasing age, body weight greater than 75 kg. and, especially, the presence of previous cardiovascular disease represented adverse factors in the development of cardiovascular toxicity.

Topics: Aged; Body Weight; Cardiovascular Diseases; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Europe; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation; Time Factors

Patients with previously untreated category T3 to T4 Mo or Ml prostatic cancer were allocated randomly to receive 250 mg. cyproterone acetate per day, a loading dose of 500 mg. medroxyprogesterone acetate intramuscularly 3 times weekly for 8 weeks followed by 100 mg. orally twice daily, or 1 mg. diethylstilbestrol 3 times daily in a phase III trial (protocol 30761) performed by the genitourinary tract cooperative group of the European Organization for Research on the Treatment of Cancer. Of 236 patients entered 210 were eligible: 75 received cyproterone acetate, 71 medroxyprogesterone acetate and 64 diethylstilbestrol. Local and distant tumor response, time to progression, survival and toxicity were assessed. Patients treated with medroxyprogesterone acetate had a less favorable course with a shorter duration of survival and time to progression than those treated with the other 2 drugs. There was no significant difference between diethylstilbestrol and cyproterone acetate. Cardiovascular side effects were reported more often in patients treated with diethylstilbestrol than in those treated with cyproterone acetate but severe and lethal cardiovascular toxicity was relatively low in all groups. Other side effects were negligible. Further studies are required to establish the influence of effective hormonal treatment upon survival.

Topics: Aged; Bone Neoplasms; Carcinoma; Cardiovascular Diseases; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Europe; Follow-Up Studies; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Middle Aged; Prostatic Neoplasms; Random Allocation

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.

Topics: Aged; Androgen Antagonists; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Drug Therapy, Combination; Ergolines; Humans; Lisuride; Male; Middle Aged; Neoplasm Staging; Prolactin; Prostatic Neoplasms

Topics: Antineoplastic Agents; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Double-Blind Method; Humans; Male; Prognosis; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Random Allocation

Topics: Castration; Clinical Trials as Topic; Cyproterone; Diethylstilbestrol; Estramustine; Humans; Male; Medroxyprogesterone; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation

Six prospective studies in the field of prostatic carcinoma have been carried out to date by the EORTC Urological Group. In three phase II studies, adriamycin, procarbazine, vindesine, and mitomycin C have been studied. Two of the three protocols have been completed. In three phase III studies, 3 mg of diethylstilbestrol (DES) is compared to cyproterone acetate (CPA), medroxyprogesterone acetate (MPA), and Estramustin phosphate (Estracyt). These two protocols have been closed to entry. The current protocol compares DES, 1 mg, to castration and to cyproterone acetate plus castration. From the phase II studies, no drug has emerged that is recommended for treatment of hormone-resistant prostatic cancer. The endocrine protocols, designed for the primary treatment of T3, T4, and M1 carcinoma of the prostate, have resulted in several important observations. Responses to DES, 3 mg/day, and to Estracyt were very similar and amounted to 25-30%. There was somewhat less objective response in the CPA and significantly less (P = 0.005) in the MPA group. It has become evident that DES at a dosage of 3 mg/day carries a significantly higher risk of overall cardiovascular toxicity than does cyproterone acetate, but severe cardiovascular complications did not differ between treatment groups. Up to now, no differences in survival were observed within the different treatment groups. Grade, local tumor extension, and performance were found to have a significant impact on survival.

Topics: Castration; Clinical Trials as Topic; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Doxorubicin; Estramustine; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Mitomycin; Mitomycins; Procarbazine; Prostatic Neoplasms; Random Allocation; Vinblastine; Vindesine

12 patients with troublesome hot flushes after orchidectomy (as a primary treatment for prostatic carcinoma) were treated with cyproterone acetate or placebo in a double-blind cross-over trial. The frequency of hot flushes was significantly reduced during the three weeks that cyproterone acetate (100 mg three times a day) was given. 5 patients complained of lassitude while on cyproterone acetate, but in none was it necessary to discontinue treatment.

Topics: Aged; Androgen Antagonists; Castration; Climacteric; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Double-Blind Method; Flushing; Humans; Male; Middle Aged; Prostatic Neoplasms; Random Allocation

Thirty-four previously untreated patients with advanced prostatic carcinoma, histologically graded as being of intermediate differentiation, were randomized in three groups. All patients were treated with primary orchiectomy, group I was observed without additional therapy, group II treated with oral administration of prednisone and group III treated with cyproterone acetate per os. The clinical results with the combination orchiectomy and prednisone was encouraging both when initial and secondary remissions were considered. Cyproterone acetate treatment induced a highly significant raise in plasma prolactin, a fact which may explain the less favourable clinical results in this group.

Topics: Adenocarcinoma; Aged; Castration; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Humans; Male; Prednisone; Prostatic Neoplasms; Random Allocation

Sixteen patients aged from 50 to 79 years with inoperable prostatic cancer were allocated at random to treatment either with 300 mg cyproterone acetate at weekly intervals or with 100 mg oestradiol-17 beta-undecylate every month. Blood samples were taken before treatment and at monthly intervals during the 6-month period of treatment. Serum prolactin levels were determined by a double-antibody radioimmunoassay. Basal serum levels of prolactin were 7.76 +/- 4.84 ng/ml and 9.50 +/- 4.32 ng/ml in the two groups of patients before therapy with oestradiol-17 beta-undecylate or cyproterone acetate, respectively. These pretreatment serum prolactin levels were statistically indistinguishable. Serum prolactin levels did not rise significantly during the first 5 months of treatment with cyproterone acetate, although an increase in prolactin was found in the sixth months of therapy with the antiandrogen. On the other hand, oestradiol-17 beta-undecylate raised serum prolactin levels significantly already after one month of treatment and the mean values were significantly higher than in the antiandrogen-treated group. These data combine to suggest cyproterone acetate as a suitable alternative to oestrogens in the therapy of inoperable prostatic cancer.

Topics: Aged; Cyproterone; Estradiol; Humans; Male; Middle Aged; Prolactin; Prostatic Neoplasms; Radioimmunoassay

Two parallel prospective randomized studies have been undertaken by the EORTC Urological Group in previously untreated patients with prostatic cancer in order to compare low dose Stilboestrol versus Cyproterone acetate versus Medroxyprogesterone acetate in the first trial, and Stilboestrol versus Estracyt in the second trial. Although the follow up is still short, no superiority of the other drugs over Stilboestrol had appeared so far with regard to either objective response or significant side effects apart from gynaecomastia. In the third trial, patients with advanced disease no longer responsive to hormonal treatment were randomized to either Adriamycin or Procarbazine. Toxicity and early death were particularly frequent in Procarbazine treated patients, whereas most patients progressed in both treatment groups.

Topics: Cyproterone; Diethylstilbestrol; Doxorubicin; Estramustine; Humans; Male; Medroxyprogesterone; Prostatic Neoplasms

Forty-two patients with previously untreated T3/4 N1-4 MO/1 prostatic adenocarcinoma were treated with either cyproterone acetate (n = 21; 300 mg intramuscularly per week) or oestradiol undecylate (n = 21; 100 mg intramuscularly per month) after extensive staging which included open skeletal biopsy and pelvic lymphadenectomy in some cases. Subjective and objective parameters as well as signs of drug toxicity were recorded regularly. Evaluation after 6 months showed cyproterone acetate to be more effective in the following respects: (1) the significantly different castration effect as judged by plasma testosterone, (2) the objective voiding pattern and tumour response, with regression of palpable and histologically evaluable local tumour in 16 of 21 patients, and (3) side effects and untoward reactions. Thus cyproterone acetate is suggested as a valuable alternative in the treatment of advanced prostatic cancer.

Topics: Adenocarcinoma; Aged; Clinical Trials as Topic; Cyproterone; Estradiol; Humans; Male; Middle Aged; Prostatic Neoplasms; Random Allocation; Time Factors

Since prolactin has several modes of action on prostatic growth and physiology, the effect of the antiprolactin bromocriptine on plasma kinetics and intraprostatic metabolism of testosterone was studied in patients with untreated prostatic cancer; a therapy protocol was deduced which was controlled in 27 patients with advanced inoperable prostatic adenocarcinoma. Bromocriptine resulted in a significant suppression of prolactin and testosterone as well and favored testosterone elimination from the plasma pool. Prostatic androgen uptake was enhanced and the intraprostatic metabolism altered in relation to tumor grade. Adjunctive administration of bromocriptine to 27 patients, mostly in the state of hormone resistance, resulted in an overall objective regression of 22.2% and in stable disease in 55.6% of the patients. In half of the individuals a prompt relief of bone pain from osseous metastases was observed as well as improvement of micturition and decline of phosphatase activity. This preliminary data justify further investigations under controlled and randomized conditions.

Topics: Adenocarcinoma; Aged; Androgens; Bromocriptine; Clinical Trials as Topic; Cyproterone; Humans; Male; Middle Aged; Palliative Care; Prolactin; Prostate; Prostatic Neoplasms; Testosterone

Sex hormone binding globulin (SHBG) binding capacity, the concentrations of testosterone (T), of 5alpha-dihydrotestosterone (DHT), of oestradiol-17beta (Oe2), of oestrone (Oe1), of prolactin (hPr) and the percentual specific binding of T to SHBG (%TB) were measured in plasma of patients suffering from prostatic carcinoma and of a control group of similar age. No significant differences in any of the investigated parameters were found between the control group and the carcinoma patients before treatment although 15% of the latter showed distinctly elevated hPr values. Treatment of carcinoma patients with 1) Antiandrogen (cyproterone acetate, Androcur) resulted in a significant decrease of T, Oe2 and SHBG. The DHT/T-ratio increased. n=5. 2) Orchidectomy caused an even more pronounced fall in T, DHT, Oe1 and Oe2 blood levels. SHBG was not altered. DHT/T-ratio increased. n=32. 3) Cyproterone acetate after orchidectomy led to elevated hPr values. n=5. 4) Oestrogen (diethylstiboestrol-diphosphate, Honvan) after orchidectomy increased SHBG and hPr. n=6. 5) Corticosteroid (Prednisone, Decortin) after orchidectomy decreased T and SHBG below the levels found after orchidectomy alone. n=5. 6) Diureticum (Mefruside, Baycaron) (n=5) or 7) a placebo (n=7) did not alter any of the parameters measured. 8) Treatment with HCG (Primogonyl) of patients suffering from oligozoospermia resulted in a significant increase of T, DHT and Oe2. SHBG was not altered. DHT/T-ratio decreased. n=7.

Topics: Chorionic Gonadotropin; Clinical Trials as Topic; Cyproterone; Diethylstilbestrol; Dihydrotestosterone; Estradiol; Humans; Male; Mefruside; Prednisone; Prolactin; Prostatic Neoplasms; Sex Hormone-Binding Globulin; Testosterone

Topics: Administration, Oral; Alanine Transaminase; Androgen Antagonists; Aspartate Aminotransferases; Bilirubin; Blood Urea Nitrogen; Clinical Trials as Topic; Creatinine; Cyproterone; Humans; Kidney; Liver; Male; Middle Aged; Oxidoreductases; Pregnadienes; Prostatic Neoplasms; Sorbitol; Sulfobromophthalein; Thymol

Quaternary prevention has been commonly defined with the "primum non nocere" of classical texts by many authors. The daily life of our primary care consultations are full of patients in which we wondered if we try to obtain the benefit of our intervention will exceed the damage we cause him to intervene. Patients with multiple comorbidities, polypharmacy and complex are common in our consultations and it is becoming more difficult to move the balance of our actions, diagnostic or therapeutic benefit to the side. Through 2 cases often move to the reflection of this problem. Quaternary prevention must also be present in our daily activities.

Topics: Aged, 80 and over; Androgen Antagonists; Anilides; Bone Density Conservation Agents; Cyproterone; Female; Humans; Inappropriate Prescribing; Indoles; Male; Nitriles; Osteoporosis; Primary Health Care; Prostatic Neoplasms; Tosyl Compounds

Our goal was to study the hormonal regulation of immune cell infiltration in prostate cancer patients treated by androgen deprivation therapy (ADT) using an optimized computer-assistance quantification approach.. The relative density of immune cell subtypes (CD3(+), CD8(+), CD20(+), CD56(+), CD68(+) and Foxp3(+)) was analyzed by immunohistochemistry in archived prostate specimens from control patients (radical prostatectomy only, n=40) and ADT-treated patients (ADT prior to radical prostatectomy, n=35) using an image analysis software and a whole-slide scanner.. ADT-treated patients had significantly increased relative density of CD3(+) (p<0.001) and CD8(+) T lymphocytes (p<0.001) as well as CD68(+) macrophages (p<0.001). Elevated abundance of CD56(+) Natural Killer (NK) cells was associated with a lower risk of prostate cancer progression (p=0.044), while a high density of CD68(+) macrophages was related to an increased risk of biochemical recurrence (p=0.011).. Our results demonstrate that the infiltration of specific immune cell subtypes is modulated by ADT. Furthermore our data confirm that NK cells have a protective role against tumor progression while macrophages seem to favor the development of advanced prostate cancer.

Topics: Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Cyproterone; Flutamide; Humans; Killer Cells, Natural; Leuprolide; Lymphocytes, Tumor-Infiltrating; Macrophages; Male; Neoplasm Recurrence, Local; Prostatic Neoplasms; T-Lymphocytes

Prostate carcinoma is one of the most frecuent cancers in men. Significant numbers of patients have regional lymph node and bone metastases during the course of the disease. Mediastinal lymphadenopathy and cutaneous metastases are uncommon and signify well-advanced disease. We report the case of a patient with prostate cancer who develops mediastinal lymphadenopathy, pulmonary nodules and cutaneous metastases 8 years after the diagnosis.

Topics: Adenocarcinoma; Androgen Antagonists; Androgens; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyproterone; Diphosphonates; Estramustine; Fatal Outcome; Flutamide; Humans; Imidazoles; Ketoconazole; Lung Neoplasms; Lymphatic Metastasis; Male; Mediastinum; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Radionuclide Imaging; Skin Neoplasms; Triptorelin Pamoate; Zoledronic Acid

Topics: Aged; Alanine Transaminase; Androgen Antagonists; Cyproterone; Gastrointestinal Agents; Glutamyl Aminopeptidase; Humans; Lactulose; Liver; Liver Failure, Acute; Liver Function Tests; Male; Prednisolone; Prostatic Neoplasms; Treatment Outcome

Late chronic side effects of the rectum constitute one of the principal limiting factors for curative radiation therapy in patients with prostate cancer. The purpose of the study was to determine the impact of immediate androgen deprivation (IAD) prior to conformal radiotherapy on rectal volume exposed to high doses, as compared with a deferred treatment strategy (DAD). Twenty-five patients (13 in the IAD group and 12 in the DAD group) with bulky tumours of the prostate, T3pN1-2M0 from the prospective EORTC trial 30846 were analysed. Three-dimensional conformal radiation treatment plans (3DCRT) using a 4-field box technique were generated based on the digitized computed tomographic or magnetic resonance findings acquired during the first 9 months after inclusion in the EORTC trial. Dose-volume histograms (DVHs) were calculated for the prostate and rectum. In the DAD group, there was no obvious alteration in the mean size of the prostate or other evaluated structures. In the IAD patients, a statistically significant reduction of approximately 40% of the gross tumour volume (GTV) was reached after a 6 months' course of hormonal treatment (p < 0.001). High-dose rectal volume was correlated with the volume changes of the GTV (p < 0.001). Mean rectal volume receiving 95% or more of the target dose was significantly reduced by 20%. Our study confirms the effect of downsizing of locally advanced prostate tumours following AD treatment and demonstrates the interdependence of the high-dose rectal volume with the volume changes of the GTV. However, the mean beneficial sparing of rectal volume was outweighed in some patients by considerable inter-patient variations.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Cyproterone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms; Radiotherapy Dosage; Radiotherapy, Conformal; Rectum

Prostate secretory granules (PSG) represent the basic secretory unit of the prostate gland, containing many of its exocrine proteases. Recent analysis of intraluminal corpora amylacea, a proposed by-product of PSG secretion, detected sulfated glycosaminoglycans (GAG) possibly keratan sulfate (KS), indicating a secretory mechanism for GAG in the human prostate surface epithelial cell.. Immunostains using anti-KS and anti-prostate-specific antigen (PSA) were evaluated on 10 sequential radical prostatectomy specimens, three of which had received neoadjuvant antiandrogen therapy. Extracts of normal secretory tissue as well as a sample composed almost entirely of prostatic stroma were subjected to Western blot analysis, using the same antibody panel.. Keratan sulfate secretion from the normal prostate epithelial cell has been confirmed and correlates, as does PSA, with the presence of cytoplasmic PSG. No such correlation exists in most adenocarcinomas or in benign epithelium after androgen ablation. Western blot analyses confirmed tissue immunostains and demonstrated a secretory proteoglycan of 70-95 kDa.. Recognition of PSG heralds a novel secretory mechanism within the human prostate gland that is linked to the secretion of KS. The role of KS in normal prostate secretion remains unknown, although it appears downregulated in neoplastic and androgen-ablated cells.

Topics: Aged; Androgen Antagonists; Blotting, Western; Cyproterone; Cytoplasmic Granules; Electrophoresis, Polyacrylamide Gel; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Keratan Sulfate; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

To determine the efficacy, safety and feasibility of intermittent androgen deprivation (IAD) in patients with prostate-specific antigen (PSA) relapse after radical prostatectomy or with an incidental prostate cancer (pT1B) after transurethral resection of the prostate (TURP).. Open, nonrandomized, prospective pilot study using the luteinizing hormone-releasing hormone analogue (LH-RHa), leuprorelin acetate (1-month depot) and cyproterone acetate.. Forty-four patients have been enrolled. After a 30-64 months' follow-up no progression to androgen-independent status has been observed. Of the entire observation period, 26.6 months (44-58%) remained treatment-free. During the treatment-free periods, normal testosterone levels were obtained, resulting in a cessation of the symptoms of androgen suppression and an improvement in quality of life.. These results indicate that IAD is an effective and feasible therapy in patients with early stages of prostate cancer. Larger trials are necessary to confirm these encouraging results. Therefore, a European prospective, randomized, multicenter study (RELAPSE study) has been started to compare IAD with continuous androgen blockade in terms of time to tumor progression, safety and quality of life in patients with PSA relapse after radical prostatectomy.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Cyproterone; Drug Administration Schedule; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Testosterone

Topics: Androgen Antagonists; Cyproterone; Hemolytic-Uremic Syndrome; Humans; Male; Middle Aged; Plasma Exchange; Prostatic Neoplasms

Relapsing polychondritis is a chronic rheumatologic disorder of unknown etiology. Cutaneous manifestations occur in nearly half of the patients and often precede cartilaginous involvement. We present the case of a man with a history of prostatic adenocarcinoma who underwent monthly injections of goserelin (Zoladex), an LH-RH analogue. Five months after the beginning of the treatment, he presented cutaneous manifestations, which then recurred monthly, after each goserelin injection. After goserelin interruption and replacement with another treatment (cyproterone acetate), the patient was asymptomatic for 2 months. A cutaneous relapse then occurred followed by a typical cartilaginous involvement. In our observation, goserelin seems to have triggered the cutaneous manifestations of relapsing polychondritis. An hormonal precipitating factor in relapsing polychondritis has already been suggested by reports of patients whose disease worsened under chorionic gonadotropin treatment or during pregnancy.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cartilage Diseases; Cyproterone; Drug Eruptions; Erythema; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Polychondritis, Relapsing; Prostatic Neoplasms; Purpura; Recurrence

A fall in the PSA level after stopping antiandrogens has been described at the stage of hormonal escape of prostatic cancer treated by complete androgen inhibition. The authors report a new case. The patient was offtially treated by pulpectomy and nitulamide for N+ prostatic carcinoma (PSA: 165 ng/ml). At the stage of hormonal escape, discontinuation of nitulamide induced a reduction of the PSA. Replacement of nitulamide by cytoproterone acetate was followed by a renewed increase of PSA, which again decreased after stomming cyproterone acetate. Three years later, the PSDA level was 3.5 ng/mg. This syndrome is probably due to mutation of the androgen receptor. In hormonal escape, suspension of all antiandrogens apart from LHRH analogues is recommended and can be followed by a temporary fall of PSA. No other antiandrogen must be administered in the place of the previous drug.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Cyproterone; Humans; Imidazoles; Imidazolidines; Lymphatic Metastasis; Male; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Substance Withdrawal Syndrome

We undertook a retrospective review of patients presenting with apparently localised prostatic carcinoma to a single practitioner for consideration of radiation therapy to clarify the characteristics of those patients who might benefit from the use of neo-adjuvant androgen deprivation. Of 133 patients referred between January 1989 and June 1994, 85 were considered suitable for radical therapy, of whom 31 were treated with hormone therapy prior to radiotherapy, frequently on the basis of an elevated PSA. Increasing PSA levels (p = 0.0016) and Gleason grade (p = 0.026) were independent variables for relapse. It was possible to define three prognostic groups of patients, on the basis of initial PSA and Gleason grade. Those of intermediate risk (PSA < 10 micrograms/l, Gleason score 8-10; PSA 10-25 micrograms/l, Gleason 5-7 or 8-10; PSA > 25 micrograms/l, Gleason score 2-4) had a superior duration of disease-free survival if given initial hormone therapy. This group of patients is potentially the most likely to benefit from such an approach and should be enrolled in prospective randomised studies of neoadjuvant androgen deprivation.

Topics: Aged; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Carcinoma; Chemotherapy, Adjuvant; Cyproterone; Disease-Free Survival; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Retrospective Studies; Risk Factors; Survival Rate

The presentation of prostatic carcinoma with pulmonary metastases is unusual. The patient reported here presented with nodular lung metastases from an unknown primary site and 3.5 years later became symptomatic with a prostatic carcinoma. Subsequent hormonal therapy led to radiological regression of the pulmonary metastases. This case report demonstrates the progression of asymptomatic prostatic lung metastases with time and their response to delayed hormonal therapy, which is discussed.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cyproterone; Follow-Up Studies; Humans; Lung Neoplasms; Male; Neoplasms, Unknown Primary; Prostatic Neoplasms; Remission Induction

Topics: Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Cyproterone; Flutamide; Humans; Imidazoles; Imidazolidines; Male; Meta-Analysis as Topic; Prostatic Neoplasms

Topics: Aged; Aged, 80 and over; Carcinoma; Chemical and Drug Induced Liver Injury; Cyproterone; Humans; Male; Prostatic Neoplasms

Topics: Aged; Chemical and Drug Induced Liver Injury; Cyproterone; Humans; Male; Prostatic Neoplasms

Preoperative hormonal therapy has been recently advocated, but remain controversial. The aim purpose is to achieve downstaging, downgrading and improvement of the surgical results. In the last 80 patients undergoing radical retropubic prostatectomy, 28 had preoperative androgen deprivation, for a period ranging from 2 to 12 months with a mean treatment time of 3 months. Medical castration was obtained with total androgen deprivation. Return to normal value of PSA level in 90% cases and to undetectable level (< 0.25) in 39% of cases, expressing probably reduction of the tumor activity. Total prostatic volume is reduced by 30-50% after three months of treatment. The operative procedure was facilitated by an easier dissection, reducing operative time and blood loss. Recovery of postoperative continence was achieved in a significantly shorter period of time (3 months) as compared with the untreated patients (9 months). Immediate continence was obtained in 70% of patients treated preoperatively. No tumor was found in one specimen but no change was observed in the histological grading of the tumor in all the patients. This present study indicates the interest of a large scale randomized study, in order to show the real benefits of neoadjuvant hormonal treatment in prostate cancer patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Cyproterone; Gonadotropin-Releasing Hormone; Humans; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms; Retrospective Studies

Sixty-eight patients who underwent radical prostatectomy without or after neo-adjuvant hormonotherapy for B2 or C stage prostate cancer were evaluated as concerned to the ease of the surgical procedure. Although it is difficult to assess this parameter, we experienced more difficulties and blood loss was higher in patients who had preoperative hormonal deprivation. Ongoing randomized trials could demonstrate an oncological benefit of neo-adjuvant hormonotherapy before radical prostatectomy. This eventual benefit will have to be balanced against an increased surgical difficulty.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Blood Loss, Surgical; Chemotherapy, Adjuvant; Cyproterone; Estramustine; Flutamide; Humans; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms

Fifteen years ago we embarked on a treatment protocol for prostatic cancer patients with widespread disease (Stage D2) which included both hormonotherapy (i.e., orchiectomy and diethylstilbestrol [DES] 5 mg/day--later substituted with cyproterone acetate [CPA] 0.2 g/day) and chemotherapy (cyclophosphamide and 5-fluorouracil 10 mg/kg/week). The rationale for such an approach was the universally poor results obtained from the conventional approach which advocated consecutive single-treatment schedules once the previous therapy had ceased to be effective. As such a conventional approach probably allowed the selection of new resistant cell clones, we assumed that perhaps an aggressive combined systemic therapeutic approach from the start, would give such a group of patients--already with generalized disease--a better long-term result. In retrospect, after fifteen years, the chemotherapy on a series of 50 patients so treated has been well tolerated with only minimal, temporary side effects. This regimen was continued up to five years with a reduced maintenance dose. The hormonotherapy was also well tolerated, and was fully maintained. Only 28 percent died of their disease (16% within the first 2 years); 28 percent died of other causes; 40 percent are still alive (14% with clinical disease). In only 9 cases was the chemotherapy discontinued for various reasons. No control arm was originally designed in this protocol, but the long-term results suggest that our original concept was probably valid. Further studies, with the possible use also of newer chemotherapeutic agents, may well justify considering this combined therapeutic approach when dealing with this disease in its widespread form.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Fluorouracil; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms; Retrospective Studies

Wistar (Cpb:WU), F344 or Sprague-Dawley rats were sequentially treated with cyproterone acetate (CA) for 21 days, testosterone propionate (TP) for 3 days, followed by a single i.v. injection of N-methyl-N-nitrosourea (MNU). One group of Wistar rats was castrated 4 weeks after MNU injection, and another group 58 weeks after MNU, when the first prostatic carcinoma was detected. Control groups received only CA + TP, CA, MNU, or they remained untreated. Early or late castration inhibited the development of atypical hyperplasia of the ventral prostate in Wistar rats. This lesion was induced by the CA + TP + MNU treatment in F344 rats, but not Sprague-Dawley rats; in Wistar rats, it was induced by CA + TP treatment, irrespective of whether MNU was given. Hypertrophic-hyperplastic lesions of the seminal vesicle were induced by MNU, irrespective of pretreatment, and their development was prevented by early castration and inhibited by late orchiectomy. Dorsolateral prostate carcinomas and preneoplasia occurred only in low incidence in Wistar and Sprague-Dawley rats. These lesions were absent in F344 rats that had received treatment with CA + TP + MNU. No dorsolateral prostate (pre)neoplasia was found in Wistar rats subjected to early orchiectomy, but rats castrated at 58 weeks had an incidence similar to that for the intact group treated with CA + TP + MNU. This finding supports the contention that androgens are required for the development of MNU-induced prostatic cancer in rats but that advanced carcinomas are androgen insensitive. Differences in incidence and localization of prostatic proliferative lesions between F344 and Wistar rats and between dorsolateral and ventral prostate could not be explained by differences in epithelial cell proliferative responses to CA + TP treatment at the time of MNU injection, since they were similar in ventral and dorsolateral prostate and were more prominent in F344 rats than in Wistar rats. DNA damage as estimated by MNU-induced unscheduled DNA synthesis also did not differ between dorsolateral and ventral prostate.

Topics: Androgens; Animals; Cyproterone; Cyproterone Acetate; DNA Replication; DNA, Neoplasm; Genital Neoplasms, Male; Male; Methylnitrosourea; Orchiectomy; Prostatic Neoplasms; Rats; Rats, Inbred F344; Rats, Inbred Strains; Seminal Vesicles; Testis; Testosterone; Time Factors

Topics: Aged; Androgen Antagonists; Angina Pectoris; Buserelin; Calcitonin; Cyproterone; Cyproterone Acetate; Flutamide; Goserelin; Humans; Hyperhidrosis; Male; Prostatic Neoplasms

A quadruple tumor marker serotest assay (neurone-specific enolase, NSE, prostate-specific antigen, PSA, prostatic acid phosphatase, PAP, and carcino-embryonic antigen, CEA) was performed on sera from both 63 patients with untreated prostate cancer and 135 patients treated with orchiectomy, flutamide, diethylstilbestrol (DES), cyproterone acetate (CPA), and Estracyt. In untreated patients with local tumor elevated blood NSE concentrations were found more frequently (10/35, 28.6%) than in untreated subjects with disseminated disease (3/28, 10.7%). Elevated NSE values were measured more frequently in nonresponders to therapy 10/46 (21.7%), than in responders during prostate cancer partial remission (2/89, 2.2%). In none of NSE-positive neoplasms a small cell prostate cancer has been histologically detected. Many of NSE-positive tumors are also closely associated with elevated blood CEA values. The applied anticancer drugs were inefficient in the normalization of neither one from the pair of elevated NSE and CEA concentrations (regardless of the numerical values of the other two markers, PSA and PAP), but their values were found to decline occasionally only after surgical treatment. In patients with raised PSA, PAP, and CEA levels but with a normal NSE value, the application of the same treatment strategies was in the most of subjects sufficient to provoke either temporary or even lasting tumor response to therapy. Hence, it appears that the assessment of the NSE serotest, despite its minimal value in the overall tumor staging and monitoring, might furnish the decision-making step related to the treatment of aggressive prostate cancer with an additional and powerful tool.

Topics: Acid Phosphatase; Antigens, Neoplasm; Antineoplastic Agents; APUD Cells; Biomarkers, Tumor; Carcinoembryonic Antigen; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Flutamide; Humans; Male; Orchiectomy; Phosphopyruvate Hydratase; Prostate-Specific Antigen; Prostatic Neoplasms

Cyproterone acetate (CPA) is a widely used drug in the treatment of advanced prostatic carcinoma. Although it is generally well tolerated, liver toxicity has been recognised as a complication of long-term use. We report 3 patients with severe hepatocellular damage due to CPA therapy, 2 with fatal fulminant hepatitis.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms

A case of stenosis of the rectum, a very rare complication of prostate cancer, is reported. One year after operation for an authentic histologically confirmed adenoma of the prostate gland, the patient progressively developed stenosis of the rectum. The prostatic origin of the stenosis was rapidly established after dilatation of the rectum and histological examination of the transrectal biopsy. Therapeutic attitudes vary according to the circumstances. Severe stenosis could lead to occlusion or subocclusion requiring temporary colostomy. Rectal dilatations have been proposed. This method was used in this case during the critical stage and to allow transrectal biopsy. Hormone therapy is the basic treatment. This pathology is extremely rare with a frequency of 2% according to certain authors and 1% in the series reported here.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Barium Sulfate; Cyproterone; Cyproterone Acetate; Enema; Humans; Male; Prostatic Neoplasms; Radiography; Rectal Diseases; Rectum

The effect of combined treatment with a GnRH agonist (buserelin depot, BUS, 6.6 mg every 2 months) with an antiandrogen (cyproterone acetate, CPA, 300 mg day-1) or a prolactin-suppressing agent (bromocriptine, BR, 20 mg day-1) on pituitary-testicular function were studied in patients with advanced prostatic carcinoma. The patients (n = 5-6 per group) were treated in this fashion for 6 months and thereafter orchidectomized. Serum testosterone and gonadotrophin responses were followed during treatment, and histology and certain endocrine parameters were studied using testicular tissue obtained at orchidectomy. Serum LH was suppressed in all treatment groups from mean levels of 4-6 IU l-1 to less than 0.1 IU l-1, whilst serum FSH levels decreased in all groups during the first month of therapy from 4.5-7 to 1-2 IU l-1, but recovered thereafter. Only minor increases in serum gonadotrophin levels were evident 3 months after castration. No differences in gonadotrophin responses were seen between the different treatment groups. Serum levels of testosterone were suppressed from 15-20 nmol l-1 to the castrate range (approximately 1 nmol l-1), in each of the treatment groups. Testicular weight decreased significantly more (P less than 0.05) in the BUS + CPA group, compared to the other treatments. No differences were found in the testicular concentration of testosterone, or LH and FSH receptors between the three treatment groups. On histological examination, spermatogenesis was found to be impaired severely in all groups, with the lowest Johnsen score in the BUS + BR group (2.16 +/- 0.13, vs. 2.73 +/- 0.25 with BUS alone, P less than 0.05). Seminiferous tubular diameters were reduced similarly in all treatment groups. In conclusion, the combination of CPA or BR with BUS in the treatment of prostatic carcinoma does not potentiate the suppression of gonadotrophin or testosterone secretion, evidently because the GnRH agonist exerts a maximal suppressing effect. However, other antigonadal effects were enhanced slightly, including suppressed testicular weights by CPA and further suppression of spermatogenesis by BR.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Bromocriptine; Buserelin; Cyproterone; Cyproterone Acetate; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Radioimmunoassay; Receptors, Gonadotropin; Testis; Testosterone

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms

Topics: Aged; Antineoplastic Agents; Carcinoma, Hepatocellular; Cyproterone; Cyproterone Acetate; Humans; Liver Neoplasms; Male; Prostatic Neoplasms

On the basis of a retrospective series of 74 patients with adenocarcinoma of the prostate, the authors study the survival of these patients according to the clinical stage of the lesion when treated with cyproterone acetate. Biologically speaking, the authors have studied the evolution of the blood testosterone level, as well as of PSA and PAPs. Their conclusion is that the PSA is an excellent indicator of the efficacy of the cyproterone acetate treatment. Its fast decrease proves treatment efficacy, while a new rise indicates the resumption of evolution of the neoplastic process and must lead to change the therapeutic approach.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Testosterone

Groups of 20-25 male Wistar rats (Cpb:WU), nine groups of 4-week-old rats, and nine groups of 8-week-old rats, were given cyproterone acetate (CA) s.c. or by gavage daily for 18 days at a dose of 50 mg/kg/day. Directly following CA treatment, the rats received 3 daily s.c. injections with testosterone propionate (TP) at a dose of 100 mg/kg/day. On the day after the last TP administration, a single dose of one of the following carcinogens was given to 3 groups: N-methyl-N-nitrosourea (MNU), 50 mg/kg i.v.; 7,12-dimethylbenz(a)anthracene, 30 mg/kg i.v.; 3,2'-dimethyl-4-aminobiphenyl, 250 mg/kg s.c. Three other groups received the same carcinogen treatments after 7 days of recovery from the CA administration. The last 3 groups received carcinogen without TP treatment, but immediately after CA pretreatment was stopped. A 25% incidence of invasively growing, metastasizing adenocarcinomas was found in the dorsolateral prostate region of 8-week-old rats that had received MNU after treatment with CA plus TP. In addition, this group had a 5% incidence of carcinoma in situ and a 5% incidence of atypical hyperplasia in the dorsolateral prostate. Lower incidences of adenocarcinoma of the dorsolateral prostate region and of carcinoma in situ and atypical hyperplasia of the dorsolateral prostate were found in other groups that were treated with MNU or 7,12-dimethylbenz(a)anthracene after pretreatment with CA, followed by TP or recovery, but never in rats that had been treated with CA only. In the groups treated with 3,2'-dimethyl-4-aminobiphenyl, which is slowly metabolized, these lesions were also found in groups that were pretreated with only CA. The carcinomas seemed to originate from the dorsolateral prostate and their average latency time was approximately 61 weeks. The 8-week-old rat given a MNU injection after sequential treatment with CA and TP may provide a relevant animal model for human prostatic cancer.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Aminobiphenyl Compounds; Animals; Body Weight; Cyproterone; Cyproterone Acetate; Genitalia, Male; Male; Methylnitrosourea; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Sarcoma, Experimental; Survival Analysis; Testosterone

A patient is described who presented with left upper lobe collapse due to endobronchial metastatic prostate carcinoma. Treatment with the oral antiandrogen cyproterone acetate resulted in resolution of the occluding endobronchial carcinoma and lobar re-expansion.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Cyproterone; Cyproterone Acetate; Humans; Lung; Lung Neoplasms; Male; Prostatic Neoplasms; Pulmonary Atelectasis

A case of severe acute hepatitis caused by cyproterone acetate in a 71 year old man with prostatic carcinoma is reported with a review of the literature on hepatic reactions to this drug. The association between the use of cyproterone acetate and liver abnormalities is poorly documented. This is the fourth published report of adverse hepatic reaction to cyproterone acetate and it substantiates other evidence that cyproterone acetate is potentially hepatotoxic. Monitoring of liver function tests should be mandatory in patients receiving high doses of cyproterone acetate; the drug should be withdrawn immediately if abnormal liver function tests are found.

Topics: Adenocarcinoma; Aged; Aspartate Aminotransferases; Bilirubin; Chemical and Drug Induced Liver Injury; Cyproterone; Cyproterone Acetate; Humans; Liver; Male; Prostatic Neoplasms

The role of transrectal ultrasonography in monitoring response of prostate cancer to treatment with ciproterone acetate is described. In our therapeutic protocol for prostate cancer, those included between categories 7 and 9 are submitted to antidrogen therapy, regardless of the type of surgical procedure indicated in each case. Fifty-one patients submitted to this treatment modality were followed using transrectal ultrasound 3 months following diagnosis and every 6 months thereafter. The mean follow-up was 2 years Using the intrinsic and morphologic ultrasound parameters we have developed at our department, we can conclude that the changes in prostate size or volume and the changes in the intensity of brightness are the most reliable parameters in assessing the response to treatment. A good response to treatment is manifested by the reduced size of prostate and reduced intensity of brightness ("dark prostate").

Topics: Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Humans; Male; Prostatic Neoplasms; Ultrasonography

The long-term effect of the luteinizing hormone-releasing hormone analogue-induced initial testosterone surge in the treatment of patients with metastatic carcinoma of the prostate still is unknown. However, acute worsening of the disease has been reported in up to 10% of the patients. To prevent such tumor flare we investigated the endocrinological effects of different types of antiandrogens administered in addition to a luteinizing hormone-releasing hormone analogue. Patients with newly diagnosed metastatic prostate cancer were pre-treated with either the steroidal antiandrogen cyproterone acetate (6) or the nonsteroidal antiandrogen flutamide (5) for 1 week before the initial injection of the depot luteinizing hormone-releasing hormone analogue Zoladex. In another 5 patients flutamide was first given 24 hours before Zoladex therapy was started. Luteinizing hormone, testosterone and prostatic acid phosphatase during month 1 of luteinizing hormone-releasing hormone analogue therapy were compared to data obtained in 5 patients treated by Zoladex alone. Only pre-treatment with cyproterone acetate was capable of preventing the Zoladex-induced testosterone surge. However, both pre-treatment regimens with either cyproterone acetate or flutamide for 1 week prevented an initial increase in prostatic acid phosphatase beyond pre-treatment levels in all patients. In contrast, in 4 of 5 patients treated with Zoladex alone and in 2 of 5 pre-treated with flutamide for 1 day an initial increase in prostatic acid phosphatase beyond the pre-treatment values was seen. Our data indicate that pre-treatment with flutamide for only 1 day may not be sufficient to prevent a luteinizing hormone-releasing hormone analogue-induced tumor flare in all cases.

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Buserelin; Cyproterone; Cyproterone Acetate; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Luteinizing Hormone; Male; Premedication; Prostatic Neoplasms; Testosterone; Time Factors

Regarding a case of little-differentiated adenocarcinoma of prostate in a 79-year old male patient undergoing antiandrogenic corticosteroid therapy (cyproterone acetate), the authors describe a rare complication related to treatment with the drug. Cytolytic icterus, without cholestasis, occurred eleven weeks after starting the treatment without metastasis of the primary cancerous lesion, and regressed when administration of the antiandrogenic agent was interrupted. This description is compatible with toxic hepatitis. This is a rare complication, which should be differentiated from stasis icterus consecutive to treatment with progestogens. Its diagnosis precludes also primary or drug-induced secondary tumors or degenerative hepatic lesions. A knowledge of this complication by the urologist is important, so the latter might not conclude too hastily to metastatic extension of primary cancer of prostate. Withdrawal of the patient from antiandrogenic therapy is mandatory, and management should incorporate complete biological investigation of liver function, CT scans and, depending upon the case, liver biopsy as the only means of studying this exceptionally rare complication.

Topics: Adenocarcinoma; Aged; Chemical and Drug Induced Liver Injury; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Cyclophosphamide; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Fluorouracil; Humans; Male; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms; Survival Rate

LNCaP cells (derived from a lymph node carcinoma of the human prostate) show androgen responsive growth. Progestagens, estradiol and antiandrogens competed with androgens for binding to the androgen receptor in the cells to a higher extent than in other androgen-sensitive systems. Optimal growth (3-4 fold increase in DNA content of 6 day cell cultures vs controls) was observed after addition of the synthetic androgen R1881 (0.1 nM). Both steroidal and non-steroidal antiandrogens did not suppress the androgen responsive growth. At a concentration of 10 nM cyproterone acetate or 100 nM RU 23908, growth was even stimulated to an extent comparable to that observed after addition of androgen. Cyproterone acetate and RU 23908 also increased the number of epidermal growth factor receptors expressed at the cell surface to a comparable level as did the androgen. Like androgens, cyproterone acetate, RU 23908 or estradiol stimulated the secretion per cell of prostate specific acid phosphatase in the culture fluid. In conclusion, antiandrogens can exert striking stimulatory effects on the proliferation of LNCaP cells probably due to a defective androgen receptor system. It is discussed that comparable changes in the specificity of the androgen receptor in prostate cancer cells may give these cells an advantage in growth rate and may contribute to development of tumors characterized as hormone independent.

Topics: Acid Phosphatase; Androgen Antagonists; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; ErbB Receptors; Estradiol; Humans; Imidazoles; Imidazolidines; Male; Prostatic Neoplasms; Tumor Cells, Cultured

The synthetic androgen mibolerone elicits a set of distinct changes in the behaviour of an androgen responsive human prostatic carcinoma cell line (LNCaP). Inhibition of cell proliferation, induction of morphological change and of a prostate specific mRNA, and inhibition of colony formation in soft agar are induced by very low concentrations of mibolerone. The natural androgen dihydrotestosterone is much less effective. The changes in growth characteristics and morphology are reverted by excess antiandrogen, i.e. cyproterone acetate or hydroxyflutamide. Cell lines lacking androgen receptors (PC-3, DU 145 and MRC-5) are completely unresponsive to mibolerone. Taken together, our results indicate androgen receptor mediated suppression of the transformed phenotype in LNCaP cells.

Topics: Androgen Antagonists; Androgens; Cell Division; Cell Transformation, Neoplastic; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Flutamide; Humans; Male; Nandrolone; Prostatic Neoplasms; Receptors, Androgen; RNA, Messenger; Tumor Cells, Cultured

Out of 17 patients who had been submitted to subcapsular orchidectomy as the primary treatment of cancer of the prostate, postorchiectomy flushing was found in eight, corresponding to 47%. Six of the patients were treated with cyproterone acetate in a dosage of 50-100 mg daily. In all of these clinically significant reduction in the frequency and duration of the flushing was found. In four out of five patients with possible recurrent flushing after withdrawal of cyproterone acetate, recommencement of the treatment proved necessary. Administration of cyproterone acetate appears to be equally effective in a dosage of 100 mg daily as in a dosage of 300 mg daily and this reduces the side effects and expenses considerably. If it is possible to obtain a more extensive patient material without hormone treatment, a placebo-controlled investigation with the reduced dosage is desirable.

Topics: Aged; Androgen Antagonists; Cyproterone; Cyproterone Acetate; Flushing; Humans; Male; Middle Aged; Orchiectomy; Postoperative Complications; Prostatic Neoplasms

Topics: Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Male; Orchiectomy; Prostatic Neoplasms; Testosterone

Topics: Aged; Cyproterone; Cyproterone Acetate; Dyspnea; Humans; Male; Prostatic Neoplasms

Topics: Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Drug Therapy, Combination; Humans; Male; Prostatic Neoplasms

Twelve patients (age range: 53-78 years) with prostatic cancer were treated with Buserelin (1.2 mg/day) and cyproterone acetate (150 mg/day). Testicular biopsies performed after 13-96 weeks of treatment were compared to those obtained from 6 untreated men of similar age. Deranged spermatogenesis was observed in all but 1 treated patient. The appearance of immature Sertoli cells and atrophic Leydig cells suggests a condition of pharmacologic 'hypophysectomy'. The variable damage to the seminiferous epithelium and findings of an incomplete involution of Leydig cells suggested a decreased but still present testicular steroidogenesis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Cyproterone; Cyproterone Acetate; Drug Therapy, Combination; Humans; Leydig Cells; Male; Middle Aged; Prostatic Neoplasms; Sertoli Cells; Spermatogenesis; Testicular Diseases; Testosterone

The relative merits of the steroidal anti-androgen, cyproterone acetate, and the non-steroidal anti-androgens flutamide and nilutamide, are reviewed. It is concluded that pure anti-androgens offer some advantages over cyproterone acetate but that they each have some features which merit improvement. A new compound which was a pure anti-androgen, peripherally selective, well tolerated with a long half-life would have significant advantages. Preclinical studies in rats and dogs show that Casodex (ICI 176,334) is a potent pure anti-androgen which is well tolerated and has a long half-life. Casodex induces marked regression of the prostate yet fails to cause the substantial elevation in serum LH and testosterone seen with flutamide and nilutamide; it is thus peripherally selective. Casodex is as effective as surgical or medical castration with Zoladex in limiting the growth of the transplantable androgen-responsive Dunning rat prostate tumour. Such a profile makes Casodex a strong candidate as the future anti-androgen of choice for the treatment of prostate cancer and benign prostate hypertrophy.

Topics: Androgen Antagonists; Anilides; Animals; Cyproterone; Cyproterone Acetate; Dogs; Flutamide; Imidazoles; Imidazolidines; Male; Nitriles; Prostatic Neoplasms; Rats; Tosyl Compounds

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Busulfan; Cyproterone; Cyproterone Acetate; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Neoplasms, Multiple Primary; Prostatic Neoplasms; Remission Induction

This study undertaken on antiandrogens alone or in combination for treatment of prostate cancer shows the efficacy of flutamide in advanced prostate cancer. At 6 and 12 months after beginning treatment, 37% of the patients showed an objective response. Patient follow up at 2 and 3 years revealed a partial response in 33% and 19%, respectively. In one patient with stage C carcinoma, a long-lasting complete response was achieved, with a duration of approximately 3 years. A marked palliative effect was observed. Transrectal ultrasound revealed prostate volume had decreased in 73% of the patients and 86% showed functional improvement. Sexual function was not substantially altered during treatment. Similarly, there was no dramatic increase in serum testosterone. The foregoing findings demonstrate that flutamide monotherapy is an effective treatment for prostatic cancer and can be chosen for younger patients who wish to conserve their sexual potency.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Flutamide; Follow-Up Studies; Humans; Imidazoles; Imidazolidines; Male; Middle Aged; Neoplasm Staging; Nitriles; Orchiectomy; Prostatic Neoplasms; Tosyl Compounds

In order to assess the androgenic activity of synthetic progestins currently used as "antiandrogens" for the treatment of prostate cancer in men, the effect of a series of these compounds has been studied in mice on the growth of the androgen-sensitive Shionogi tumor. Female mice (DD/S strain) were inoculated subcutaneously with 10(6) viable cells and divided into groups who received, respectively, the synthetic "progestins" medroxyprogesterone acetate (MPA), megestrol acetate (MEG), cyproterone acetate (CPA) or chlormadinone acetate (CMA), compared with the non-steroidal antiandrogen Flutamide (Flu), each administered at the twice-daily dose of 250 micrograms. Each synthetic "progestin" exerted a marked stimulatory effect on the growth of the tumor. The most impressive effect on growth was observed with MPA. In fact, in MPA-treated mice, tumor size was 17 times larger than control at 4.92 +/- 0.36 cm2/mouse 21 days after inoculation. CPA, CMA and MEG also stimulated the growth of this androgen-sensitive tumor, the percentages of stimulation of tumor size being 3.1-, 3.2- and 11.0-fold above control, respectively, on day 21, while Flu had no significant stimulatory effect. The present data clearly show that all the above-mentioned progestins have variable levels of stimulatory activity on the growth of the androgen-sensitive Shionogi tumor and indicate that such drugs are unlikely to be recommendable for the treatment of prostate cancer.

Topics: Androgens; Animals; Chlormadinone Acetate; Cyproterone; Cyproterone Acetate; Female; Flutamide; Male; Mammary Neoplasms, Experimental; Medroxyprogesterone; Medroxyprogesterone Acetate; Megestrol; Megestrol Acetate; Mice; Progesterone Congeners; Prostatic Neoplasms

The effects of the s.c. administration of a depot formulation of the luteinizing hormone-releasing hormone (LHRH) analogue Zoladex were studied in normal male rats, alone and in combination with three drugs with "antiandrogenic" action (ketoconazole, cyproterone acetate, and RU 23908) on prostatic weight and on circulating hormone levels in order to investigate whether these antiandrogens might prevent the LHRH-A-induced initial increase in these parameters. These effects were compared with those caused by surgical castration. In addition the effects of the antiandrogens on the activity of the hypothalamic-pituitary-adrenal axis were investigated. The depot LHRH analogue caused an initial increase in ventral prostatic weight after 4 days but suppressed the prostatic and testicular weights, the pituitary luteinizing hormone (LH) content, and plasma LH and testosterone levels after 10 and 17 days. All three antiandrogenic drugs used prevented the initial LHRH analogue-induced rise in prostatic weight, while RU 23908 suppressed its weight after only 4 days. After 10 and 17 days cyproterone acetate and RU 23908 had a similar significantly greater suppressive effect on prostatic and testicular weights than the LHRH analogue alone, while the additive inhibitory effect of ketoconazole was smaller. Surgical castration suppressed prostatic weight significantly more after 4 days, while its effects after 10 and 17 days were similar to that exerted by the combination of LHRH-A and RU 23908. The antigonadotropic effect of cyproterone acetate and the indirect gonadotropin-stimulating effects of ketoconazole and RU 23908 were not recognized in rats simultaneously treated with the LHRH analogue and did not interfere with the LHRH analogue-induced rapid depletion of the pituitary LH content and the decrease in circulating LH and testosterone levels. The LHRH analogue stimulated circulating progesterone and suppressed 17-hydroxyprogesterone levels. Ketoconazole and cyproterone acetate caused disorders in the pituitary-adrenal axis via different mechanisms: ketoconazole caused adrenal hypertrophy with normal circulating corticosterone levels caused by a compensatory increase in ACTH secretion; while cyproterone acetate exerted glucocorticoid-like effects causing a depletion of the pituitary adrenocorticotropic hormone content, adrenal atrophy, and lowered corticosterone levels. The addition of RU 23908 did not change the LHRH agonist-induced changes in adrenocortical activi

Topics: Adrenocorticotropic Hormone; Animals; Buserelin; Cyproterone; Cyproterone Acetate; Delayed-Action Preparations; Goserelin; Imidazoles; Imidazolidines; Ketoconazole; Luteinizing Hormone; Male; Orchiectomy; Organ Size; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Strains

45 patients with recently detected prostatic cancer were treated with cyproterone acetate (CPA) at a dosage of 100 mg/die. 25 patients underwent primary orchiectomy and consecutive treatment with 200 mg CPA/die. In 44.4% of the 45 patients who underwent monotherapy with 100 mg CPA/die progression of cancer was observed 10.8 months after beginning of treatment on average 55.6% of these patients showed a remission or stabilisation. 7 patients died, 4 certainly due to prostatic cancer. In the 25 patients who underwent orchiectomy and treatment with 200 mg CPA/die, 92% showed a remission. One patient of this group died, but not as a result of cancer. Based on the present data it may be concluded that treatment of inoperable prostatic cancer with 100 mg CPA as monotherapy is not indicated in patients with poorly differentiated tumours. Combination therapy--in addition to other possibilities of contrasexual therapy in prostatic cancer--seems to be of high efficacy.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Humans; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prostatectomy; Prostatic Neoplasms

Controversy still exists as to whether oestrogens exert a direct effect on the prostatic cell. Incorporation of 75Selenomethionine (SeM) was used as a measure of protein synthesis by prostatic carcinoma cells in vitro to investigate the action of hormones on prostatic carcinoma cells in tissue culture. Stilboestrol (DES) and stilboestrol diphosphate (Honvan) inhibited protein synthesis in a proportion of patients, while testosterone was stimulatory. A similar effect was noted in cells from patients with benign hyperplasia (BPH). This work confirms that oestrogens have a direct inhibitory effect on prostatic cells at high concentrations which can be attained in patients given intravenous stilboestrol diphosphate.

Topics: Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estradiol; Humans; Male; Neoplasm Proteins; Prostatic Neoplasms; Selenomethionine; Testosterone; Tumor Cells, Cultured

Topics: Aged; Androgen Antagonists; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Humans; Male; Neoplasm Staging; Prostatic Neoplasms

Topics: Acid Phosphatase; Androgen Antagonists; Bone Neoplasms; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Humans; Male; Neoplasm Staging; Prostatic Neoplasms; Radionuclide Imaging; Retrospective Studies

Cyproterone acetate is a steroidal antiandrogen with weak progestational activity that results in the partial suppression of pituitary gonadotropin. We demonstrate that the associated decrease in serum testosterone is more complete and prolonged if cyproterone acetate (200 mg. daily) is combined with a low dose of diethylstilbestrol (0.1 mg. daily). The effectiveness of the combination in the treatment of prostatic carcinoma was investigated in 51 patients with stage D2 malignancy. From an initial concentration of 360 +/- 23 ng. per dl. (mean +/- standard error), serum testosterone decreased to 56 +/- 5 ng. per dl. after 1 week and reached a plateau of approximately 30 ng. per dl. after 2 months. This was accompanied by a decrease in serum prostatic acid phosphatase from a mean starting concentration of 43 +/- 11 ng. per ml. to a low of 3 +/- 1 ng. per ml. at 12 months; the proportion of normal values increased from 10 to 80 per cent. A complete response was observed in 7 patients (13 per cent), partial response in 35 (69 per cent) and stable disease in 8 (16 per cent), yielding an over-all objective response rate of 98 per cent (1980 National Prostatic Cancer Project criteria). The actuarial median time to progression was 17 months and the median survival time was 23.5 months. In 26 patients who subsequently had signs of progressive carcinoma the relapse rate in bone (85 per cent) far exceeded that in nonskeletal sites (23 per cent). The incidence of cardiovascular toxicity was 12 per cent. These results indicate that cyproterone acetate and low dose diethylstilbestrol may be co-administered to achieve a synergistic and potent androgen withdrawal effect in the treatment of advanced prostatic carcinoma.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Drug Evaluation; Drug Synergism; Gonadotropins, Pituitary; Humans; Male; Middle Aged; Pilot Projects; Prostatic Neoplasms; Testosterone

Thirty-six patients with advanced prostatic cancer were treated by monthly depot injections of a luteinizing-hormone releasing hormone analogue (LHRH-a). Five of these patients were also pretreated for 14 days with cyproterone acetate (CPA) in order to counteract initial increase in testosterone concentration. Two weeks after the initial depot injection the serum testosterone had been reduced to and was maintained at castrate level. Luteinizing hormone and follicle stimulating hormone were also significantly reduced. Of the 31 patients 23 showed objective regression at 3 months, 9 had stable disease and none showed progression. At 3 months 22 patients reported subjective improvement. At 12 months 18 showed objective regression, 7 had withdrawn from therapy and 6 showed progression. Side effects were acceptable and comparable to those following surgical castration. It is shown that CPA counteracts the initial increase in testosterone concentration at initiation of LHRH-a treatment. We conclude that depot preparations of LHRH-analogues, both with and without pretreatment with CPA, are useful in the treatment of patients with advanced prostatic cancer.

Topics: Aged; Aged, 80 and over; Buserelin; Cyproterone; Cyproterone Acetate; Delayed-Action Preparations; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone

In this paper the authors review the completed and current EORTC Genitourinary Group trials for metastatic carcinoma of the prostate. In terms of time to progression and length of survival, there is no significant difference between any of the effective endocrine treatments that have been studied. The statistical analysis of the different variables used in trials 30,761 and 30,762 determines three risk groups of patients. There is no need for very special laboratory investigations to establish a prognosis. Orchiectomy is the cheapest and safest endocrine treatment in metastatic carcinoma of the prostate.

Topics: Androgen Antagonists; Carcinoma; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Europe; Gonadotropin-Releasing Hormone; Hormones; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms

This study investigated the effect of metastatic prostatic carcinoma on bone density. Thirty patients underwent a lumbar spine scan with a dual photon absorptiometer. Of these patients, 9 had proven skeletal metastatic deposits in the area being investigated. Comparison of results with a non-matched control population with proven benign prostatic histology showed a significantly elevated linear bone mineral content (BMC) in the disease group. Patients scanned after a 3- or 6-month period of hormonal therapy demonstrated a rise in BMC values, although the trend was not statistically significant. Indices of calcium metabolism have also been investigated.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Alkaline Phosphatase; Bone and Bones; Bone Neoplasms; Calcium; Cyproterone; Diethylstilbestrol; Humans; Male; Middle Aged; Minerals; Prostatic Neoplasms

In order to assess the androgenic activity of synthetic "progestins" currently used as "antiandrogens" for the treatment of prostate cancer in men, the effect of a series of these compounds has been measured following 14 days of treatment of adult castrated rats on specific and sensitive parameters of androgenic activity, namely ventral prostate weight and prostatic ornithine decarboxylase (ODC) activity. Medroxyprogesterone acetate (MPA) is almost equipotent with 5 alpha-dihydrotestosterone (DHT), a 49% increase in prostatic weight being observed at the low dose of 0.15 mg, twice daily (P less than 0.01). Megestrol acetate (Megace), chlormadinone acetate (CMA) and spironolactone were less potent but caused a 36-59% increase in prostatic weight at the highest dose used, namely 10 mg. At the 5 mg dose, cyproterone acetate (CPA) caused a 75% increase in prostatic weight. The androgenic activity of the compounds is even more clearly illustrated by their marked stimulatory effect on prostatic ornithine decarboxylase (ODC) activity. MPA, at the low dose of 0.15 mg, caused a 20-fold increase (relative to the effect of placebo) in the activity of the enzyme while the same dose of DHT caused a 15-fold stimulation of enzymatic activity. At the 10 mg dose, megestrol acetate, CMA and spironolactone caused 13.1, 11.8 and 8.6-fold stimulations of ODC activity, respectively. Flutamide, on the other hand, had no stimulatory effect on either ventral prostate weight or prostatic ODC activity. In agreement with glucocorticoid activity, MPA, megestrol acetate and CMA caused a marked inhibition (45-64%) of adrenal weight. The present data show that MPA is a highly potent androgen while megestrol acetate, CMA, CPA and spironolactone have lower but significant androgenic activity on all the parameters measured. It should be added that MPA, megestrol acetate and CMA are completely devoid of antiandrogenic activity while spironolactone shows weak antiandrogen action and CPA is a mixed agonist-antagonist. Flutamide, the compound used as reference, is the only compound devoid of any androgenic action and is thus acting as a pure antiandrogen on both ventral prostate weight and prostatic ODC activity. The present data have major implications for the choice of drug to be used for the treatment of androgen-sensitive diseases, especially prostate cancer. As shown by the present data, the synthetic "progestins" so-far available all possess variable levels of androgenic activity and are

Topics: Adrenal Glands; Animals; Chlormadinone Acetate; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Flutamide; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Megestrol; Megestrol Acetate; Organ Size; Ornithine Decarboxylase; Progesterone Congeners; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Spironolactone

The transplantable human prostatic adenocarcinoma, PC-82, has been shown to be a suitable model for the study of several aspects of androgen-regulated tumor growth. This tumor contains an androgen receptor, and the purpose of the present investigation was to characterize this androgen receptor with respect to hormone specificity, sedimentation coefficient, dissociation constant, Stokes radius, ionic properties, and molecular mass. Cytosol was prepared from tumor tissues grown in athymic nude mice, which were castrated 10 days before harvesting the tumor. Scatchard plot analysis revealed a binding protein with a Kd of 0.1 nM for R1881 (methyltrienolone) and binding capacity of 120 fmol/mg protein. The receptor showed a high affinity for R1881, testosterone, and 5 alpha-dihydrotestosterone, respectively, whereas no or little affinity was found for progesterone and estradiol. In the presence of 10 mM molybdate the androgen receptor in PC-82 cytosol eluted from an FPLC anion exchange column (Mono Q) at 0.32 M NaCl, which is identical to what has been found for androgen receptors from rat prostate and calf uterine cytosol. Photoaffinity labeling of the [3H]R1881-androgen receptor complex and subsequent analysis on SDS-polyacrylamide gels resulted in a covalently labeled protein with a molecular mass of approximately 50 kD. The androgen receptor of the PC-82 tumor had a sedimentation coefficient of 4S and a Stokes radius of 3.3 nm at high ionic strength (0.4 M NaCl). It is concluded that the PC-82 tumor contains a binding protein with the properties described for androgen receptors present in prostate tissue.

Topics: Adenocarcinoma; Cell Line; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Estradiol; Estrenes; Humans; Male; Metribolone; Molecular Weight; Neoplasm Transplantation; Progesterone; Prostatic Neoplasms; Receptors, Androgen; Testosterone; Triamcinolone Acetonide

It has been proposed that early treatment of patients with advanced prostatic cancer by surgical or medical orchiectomy when combined with a direct acting antiandrogen will result in a more complete form of androgen blockade, thereby increasing response and survival rates compared to orchiectomy alone. We treated 55 patients with previously untreated advanced prostatic cancer by bilateral orchiectomy and additional administration of 50 mg. of the direct acting antiandrogen cyproterone acetate orally per day. Therefore, these patients have undergone a combination therapy that meets the requirements of the proposed complete androgen blockade. All 22 patients with metastases at hospitalization died during the first 4 years of treatment. Among the 33 patients without clinical evidence of metastases at hospitalization 18 were alive after 5 years. Retrospectively, the direct observed 5-year survival rate for the patients treated with a complete androgen blockade did not show any advantage compared to reported data with orchiectomy alone.

Topics: Aged; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Retrospective Studies; Time Factors

We recruited 71 previously untreated patients with metastatic prostatic carcinoma to 2 separate consecutive prospective phase 2 studies done by the same group of investigators according to the same protocols in which only the treatment regimens differed. Of the patients 58 were treated with the luteinizing hormone-releasing hormone analogue buserelin alone (0.4 mg. 3 times daily intranasally) and 13 were treated with buserelin combined with cyproterone acetate, a potent antiandrogen (50 mg. 3 times daily orally). The objective of the study was to investigate the efficacy, safety and tolerability of the medication used during at least 12 months by studying adequate endocrine parameters, the rate and duration of response, as well as the rate of progression and possible side effects. All endocrine parameters were studied in 1 laboratory. Modified response criteria of the National Prostatic Cancer Project were used. The endocrine studies showed an effective suppression of plasma testosterone to castration levels by buserelin after an initial increase during the first 2 weeks. Luteinizing hormone and follicle-stimulating hormones were lowered significantly and could not be re-stimulated by the intravenous application of luteinizing hormone-releasing hormone. There was no correlation of plasma testosterone with response and progression. However, a significant correlation existed between higher basal cortisol levels at entry, and after 3 and 6 months, and progression. Response is reported for all patients at the 12-month interval and did not seem to differ among treatment groups. The rate of progression after all patients had been treated for 1 year was 37.9 per cent in the buserelin group and 41 per cent in the buserelin plus cyproterone acetate group. Three early deaths occurred in the buserelin group. Except for impotence, only mild side effects were noted. Our study shows that treatment of metastatic prostatic cancer by means of the luteinizing-hormone-releasing hormone analogue buserelin is safe and effective. The results obtained are compatible with those obtained by castration. In our study a superiority of total androgen withdrawal over testicular suppression alone could not be shown.

Topics: Buserelin; Cyproterone; Cyproterone Acetate; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Follow-Up Studies; Humans; Male; Prospective Studies; Prostatic Neoplasms; Testosterone; Time Factors

The interaction between testosterone and calcitonin secretion capacity was studied in 9 patients with prostatic cancer. Treatment with the antiandrogenic agent cyproterone acetate resulted in an expected decrease in serum testosterone but an unexpected and unexplained increase in calcitonin secretion capacity. The previous statement that a positive correlation between sex hormones and calcitonin secretion capacity can be recognized probably requires revision. This unexpected effect of cyproterone acetate had possible additive beneficial advantages for treatment, such as bone mass sparing and its analgesic effect.

Topics: Aged; Aged, 80 and over; Calcitonin; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms; Testosterone

Topics: Buserelin; Cyproterone; Cyproterone Acetate; Goserelin; Humans; Male; Prostatic Neoplasms; Testosterone

Topics: Androgen Antagonists; Anilides; Cyproterone; Cyproterone Acetate; Flutamide; Humans; Imidazoles; Imidazolidines; Male; Prostatic Neoplasms

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cyproterone; Cyproterone Acetate; Humans; Male; Middle Aged; Prostatic Neoplasms

Topics: Biomarkers, Tumor; Castration; Cyproterone; Diethylstilbestrol; Estradiol; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms

The antiandrogen cyproterone acetate (CA), as well as oestrogens have been reported to influence pituitary-adrenal function in prostate cancer patients, but the clinical relevance of these findings is unknown. We therefore investigated serum cortisol (F), dehydro-epiandrosterone sulphate (DS), testosterone (T) and prolactin (Prl) levels in patients treated with CA or oestradiol undecylate for at least 6 months. Hypothalamic-pituitary-adrenal function was further assessed by analysis of diurnal hormone variation and by ACTH stimulation and dexamethasone suppression tests. To differentiate between direct CA or oestrogen effects and secondary effects resulting from therapy-induced hypogonadism, we performed similar tests in untreated normogonadal and hypogonadal patients. CA treatment effected a significant decrease in serum F (-40%), DS (-73%) and T (-58%) levels and an increase in serum Prl (+118%). Oestrogen treatment resulted in markedly lowered T levels (-89%), slightly elevated serum F (+24%) and significantly increased serum Prl (+192%). Corresponding changes of F, DS and Prl could not be found in the untreated hypogonadal controls, thus indicating a direct drug-related effect. Neither diurnal rhythmicity of serum F nor adrenal response to ACTH stimulation or sensitivity to dexamethasone suppression significantly changed under CA or oestrogen treatment. We conclude that, although serum F levels may decrease under CA or increase slightly under oestrogen therapy for prostate carcinoma, these findings do not justify specific treatment, since neither clinical side effects nor an impairment of hypothalamic-pituitary-adrenal feedback occurs.

Topics: Adrenal Cortex; Adrenocorticotropic Hormone; Aged; Circadian Rhythm; Cyproterone; Cyproterone Acetate; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Estradiol; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Pituitary-Adrenal Function Tests; Pituitary-Adrenal System; Prolactin; Prostatic Hyperplasia; Prostatic Neoplasms; Testosterone

Topics: Adrenalectomy; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Hypophysectomy; Ketoconazole; Male; Orchiectomy; Palliative Care; Prostatic Neoplasms

Topics: Anilides; Combined Modality Therapy; Cyproterone; Flutamide; Gonadotropin-Releasing Hormone; Humans; Male; Megestrol; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms; Receptors, Cell Surface; Receptors, LHRH

Topics: Antineoplastic Combined Chemotherapy Protocols; Bromocriptine; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Cyproterone; Cyproterone Acetate; Fluorouracil; Humans; Male; Methotrexate; Neoplasm Staging; Orchiectomy; Prognosis; Prostatic Neoplasms

Fasting serum lipoproteins were measured in 10 untreated patients with carcinoma of the prostate (Group I), 17 patients with non-malignant urological disorders (Group II), and 12 patients on cyproterone acetate (Group III) and 5 on a long-acting luteinizing hormone-releasing hormone (LHRH) analogue (Group IV) for at least 2 months for carcinoma of the prostate. Total high-density lipoprotein (HDL) cholesterol levels were significantly lower in patients in Group III than all the other groups. Very low-density lipoprotein (VLDL) triglyceride levels were significantly higher in patients in Group III than those in Groups II and IV. These results suggest a potentially adverse effect of cyproterone acetate, but not of the long-acting LHRH analogue, on serum lipids, which is likely to be of relevance only in younger patients.

Topics: Buserelin; Cyproterone; Cyproterone Acetate; Goserelin; Humans; Lipoproteins; Lipoproteins, HDL; Lipoproteins, VLDL; Male; Prostatic Neoplasms; Urologic Diseases

Organ culture of the rat ventral prostate has been evaluated as a model for studying the biological effects of androgen agonists, androgen antagonists, and estrogens. Explants were cultured for up to 8 days, and incorporation of (3H)-thymidine and (3H)-uridine by the explants was measured. Dihydrotestosterone (DHT) increased the incorporation of (3H)-thymidine/microgram DNA when compared with the untreated controls at 4 days, P less than .05; and at 6 days, P less than .01. Enhanced uptake in explants from 6 to 8-week old rats also was observed with 10 nM estradiol (P less than .05) and 10 nM cyproterone acetate (P less than .02). DHT (10 nM) caused greater enhancement of uptake in explants from 3-week-old rats than in explants from 6- or 12-week-old rats. In contrast, estradiol (E2) increased incorporation only in prostates from the 6-week-old rats. Since both DHT and E2 can enhance (3H)-thymidine uptake even though they are associated with strikingly different effects on prostate morphology, it suggests that their effects on (3H)-thymidine incorporation are mediated by different cells.

Topics: Adenocarcinoma; Age Factors; Androgens; Animals; Cyproterone; Cyproterone Acetate; Estradiol; Estrogens; Insulin; Male; Mice; Organ Culture Techniques; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testosterone

The hope of providing a safe alternative to bilateral orchiectomy for patients with prostatic cancer has spurred the development in recent years of various agents capable of reducing androgen level. Another reason for intensifying these efforts relates to the hope held by many clinicians that earlier initiation of androgen deprivation for patients with regional or distant metastases will improve the patient's course. Finally, attempts to provide a more complete androgen blockade hold the hope of delaying or preventing relapse, which usually occurs with continued androgen deprivation.

Topics: Androgen Antagonists; Cyproterone; Cyproterone Acetate; Flutamide; Humans; Male; Megestrol; Megestrol Acetate; Neoplasm Metastasis; Orchiectomy; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms

Topics: Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Prostatic Neoplasms

Hormone sensitivity, as indicated by the presence of steroid hormone receptors and by the effect of androgens and anti-androgens on the release of proteins by cultured cells of the human prostate tumor cell line lymph node carcinoma of the prostate-fast growing colony (LNCaP-FGC), has been studied. The growth of the LNCaP-FGC cells were stimulated by androgens in a dose-dependent way. Under optimal conditions the synthetic nonmetabolizable androgen 17 beta-hydroxy-17 alpha-methyl-(3H)-estra-4,9,11-trien-3-one (R1881) (0.1 nM) stimulated cell growth by approximately 2.3 times. Increasing doses of R1881 (1-100 nM) partly decreased the stimulation of the cell growth. The anti-androgen cyproterone acetate exerted inhibitory effects on cell growth. The nuclear extract of the LNCaP-FGC cells contained 17,000 +/- 2,500 (mean +/- SD) KCl-extractable, nuclear androgen receptor sites/cell. Estrogen and progesterone receptors were not detectable in the nuclear extracts nor in cytosol, indicating that these receptors were absent. The release of proteins in the culture medium was studied using incorporation of the 35S-methionine, sodium dodecyl sulfate (SDS)-gel electrophoresis, and fluorography. Cells grown in media containing charcoal-stripped fetal calf serum released significantly lower amounts of a protein with an apparent molecular mass of 42,000 daltons. The release of this 42-kD protein could be restored in cells cultured in the presence of 5 alpha-dihydrotestosterone (0.1-1 microM) or R1881 (0.1-100 nM), whereas the addition of estrogens or corticosteroids had no effect. In the presence of anti-androgens, such as cyproterone acetate and 5,5-dimethyl-3-(4-nitro-3-(trifluoro-methyl)-phenyl)-2,4-imidasolidin edione, inhibitory effects on the release of the 42-kD protein were observed. The observed parallel between the effects of (anti)-androgens on the growth of the LNCaP prostate cells and the release of the 42-kD protein suggests that this protein is involved in the regulation of malignant prostate cell growth.

Topics: Androgens; Cell Division; Cell Line; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Estrenes; Humans; Male; Metribolone; Neoplasm Proteins; Prostate; Prostatic Neoplasms; Receptors, Androgen; Triamcinolone Acetonide

Topics: Antineoplastic Combined Chemotherapy Protocols; Buserelin; Cyproterone; Diethylstilbestrol; Goserelin; Humans; Male; Prostatic Neoplasms

Antiestrogens and partial estrogens of the stilbene (1 and 4), triphenylbutene (2) and diphenylethane (3) series were tested for their potential prostatic tumor inhibiting activity. Compounds 1 and 2 exerted a strong inhibitory activity on prostate and seminal vesicle weight of intact rats and mice, whereas the strong antiestrogen 3 and compound 4 had no or only a slight effect. The tumor inhibiting activity of 1 and 2 on the hormone-dependent R 3327 Dunning prostatic carcinoma of the rat was strong and comparable to that of castration or administration of the potent estrogen DES. Compounds 1-4 had no direct antiandrogenic effect in castrated, testosterone-substituted rats and mice, and no affinity for the androgen or progesterone receptor. To the estrogen receptor from prostatic tumor cytosol, however, 1-4 had good receptor affinities. As the partial antiestrogen 1 and the partial estrogen 2 have much lower estrogenic properties than DES, but still have strong prostatic tumor inhibiting properties, they may offer a suitable alternative to conventional therapy of prostate carcinoma because of their possibly low estrogenic side effects.

Topics: Animals; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estradiol; Estrogen Antagonists; Estrogens; Genitalia, Male; Male; Mice; Organ Size; Progesterone; Prostatic Neoplasms; Rats; Stilbenes; Tamoxifen; Testosterone

Surgical castration combined to cyproterone acetate treatment in patients with advanced prostatic carcinoma, gives satisfactory clinical results in 75% of the cases, with a follow-up period of 12-59 months. Histological tumour grading, tissue dihydrotestosterone (DHT) concentrations and DNA distribution by flow-cytometry in the tumoral cells are significantly correlated with the clinical response to hormonal therapy, whilst cytosol androgen receptors are not. 17 cases with DHT levels greater than 1.8 ng/g tissue are in remission (COR, POR or OS), whereas 5 cases with DHT levels less than 1.8 ng/g are in progression. In the responder group diploid DNA pattern is found in 20 cases and aneuploidy in 7, whilst in the not responder group aneuploidy was found in 5 cases and diploidy in 2. In conclusion histological grading and measurement of DNA and DHT in tumour tissue may be complementary in the prospective identification of the hormonally dependent tumours, which may benefit of the combined endocrine therapy suppressing androgens of testicular and adrenal origin.

Topics: Aged; Aneuploidy; Cyproterone; Cyproterone Acetate; Diploidy; Humans; Male; Middle Aged; Orchiectomy; Prognosis; Prostatic Neoplasms; Receptors, Androgen

Luteinizing hormone-releasing hormone (LH-RH) analogs are an effective treatment of metastatic carcinoma of the prostate. However, they induce an initial rise in serum testosterone responsible for 10-30% of diseases flares. The efficacy of the antiandrogen cyproterone acetate (CPA) was tested in 15 patients with metastatic carcinoma of the prostate. 10 patients were given 100 mg CPA t.i.d. from day 1 to 14 in association with the LH-RH analog Buserelin, 500 micrograms t.i.d., from day 7 to 14.5 patients were given CPA and Buserelin at the same doses from day 1 to 7. Serum testosterone determinations were obtained on days 1-7, 8, 11 and 14, at 08.00 h, and on days 8, 11, 1 h after each analog injection in group 1, and on days 1, 4 and 7 at 08.00 h and 1 h after each analog injection in group 2. All the patients were then treated by orchidectomy. Pretreatment with CPA blunted the initial rise of testosterone which never rose above pretreatment levels. Simultaneous treatment had no demonstrable effects on the rise of serum testosterone. It is concluded that pretreatment with CPA allows a safer use of LH-RH analogs in the treatment of metastatic carcinoma of the prostate.

Topics: Aged; Androgen Antagonists; Buserelin; Cyproterone; Cyproterone Acetate; Drug Therapy, Combination; Humans; Male; Premedication; Prostatic Neoplasms; Testosterone

Beside orchiectomy and estrogens, other endocrine manipulations are proposed for metastatic prostatic cancer patients. Antiandrogens, Cyproterone acetate and Flutamide, are often less efficient but less toxic than DES. Progestational agents medroxyprogesterone acetate, megoestrol acetate, chlormadinone acetate have also a limited activity. Inversely, tamoxifen is very little active. Preliminary results of ketoconazole need more controls. The present aims are to obtain, particularly by hormonal association, a more efficient and less toxic treatment, when DES can be given initially or becomes inefficient.

Topics: Androgen Antagonists; Cyproterone; Flutamide; Humans; Ketoconazole; Male; Medroxyprogesterone; Megestrol; Neoplasms, Hormone-Dependent; Progestins; Prostatic Neoplasms; Tamoxifen

Topics: Buserelin; Cyproterone; Drug Therapy, Combination; Humans; Male; Prostatic Neoplasms

Of 749 patients with carcinoma of the prostate 133 (17.8%) presented with total urinary retention; 122 of the 133 patients were given different forms of endocrine therapy. Only 8 patients were treated by initial transurethral resection of the prostate, and 3 patients received no treatment. After endocrine therapy 80 (65.6%) of 122 patients were free from catheter six months after starting treatment. The response to orchidectomy appeared earlier than that to treatment with estrogens. The mean period of catheterization for the 80 patients who responded was 2.7 months after orchidectomy and 3.4 months during estrogen treatment. The difference was statistically significant (p less than 0.05).

Topics: Adenocarcinoma; Aged; Castration; Cyproterone; Cyproterone Acetate; Drug Therapy, Combination; Estradiol; Estradiol Congeners; Estrogens; Ethinyl Estradiol; Humans; Male; Middle Aged; Prostatic Neoplasms; Urethral Obstruction

52 patients with virginal carcinoma of the prostate were treated with 100 mg cyproterone acetate during an observation period of 12 to 68 months (average 38.2 months). In 7 patients (13.5%) the therapy had to be stopped because of gastrointestinal intolerability. Of 45 patients in whom a relevant clinical statement was possible 44.4% showed a progression of the disease after a period of 3 to 30 months (on average 10.8 months). 95% of these patients had carcinomas with a higher degree of malignity (GII or GIII). From this is concluded that the monotherapy of the medium- to undifferentiated carcinoma of the prostate with cyproterone acetate is to be refused in this dosage.

Topics: Aged; Antineoplastic Agents; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Humans; Male; Middle Aged; Neoplasm Staging; Prostate; Prostatic Neoplasms; Testosterone

The levels of polyamines and their synthesizing enzymes in squamous cell carcinoma of prostate implanted in intact as well as castrated male rats were determined after certain hormonal manipulations. The tumour was found to grow with an identical rate in non-castrated and castrated rats. Polyamine content and activities of polyamine synthesizing enzymes in the tumour were found to be much lower compared to their values in ventral prostate. Moreover, the levels of these parameters were comparable in tumours whether implanted in non-castrated or gonadectomized animals. The sequential analyses of putrescine and spermidine and activities of L-ornithine decarboxylase and S-adenosyl-L-methionine decarboxylase of tumours at different time intervals showed a significant reduction in their levels at 30 days compared to 10 days post implantation in non-castrated as well as castrated rats. Daily intramuscular administration of tumour-bearing intact or castrated animals with testosterone (50 micrograms/g), beta-estradiol (2 micrograms/g) or cyproterone (12.5 micrograms/g) for 10 days did not influence polyamine metabolism in tumour tissue. However, either beta-estradiol and cyproterone treatments or castration were found to decrease polyamine synthesis in ventral prostate. At the same time, the testosterone replacement therapy did not allow polyamine levels or activities of polyamine synthesizing enzymes to decline in the ventral prostate of castrated rats. Our results demonstrated that contrary to ventral prostate, the polyamine metabolism in squamous cell carcinoma of prostate is independent of hormonal control. The loss of hormonal sensitivity of polyamine metabolism in the prostatic tumour could be the result of qualitative changes that occurred during transformation.

Topics: Adenosylmethionine Decarboxylase; Androgens; Animals; Carcinoma, Squamous Cell; Castration; Cyproterone; Estradiol; Estrogens; Hormones; Male; Neoplasm Transplantation; Ornithine Decarboxylase; Polyamines; Prostatic Neoplasms; Putrescine; Rats; Rats, Inbred F344; Spermidine; Spermine; Testosterone

Topics: Androgen Antagonists; Animals; Castration; Cyproterone; Estrogens; Flutamide; Gonadotropin-Releasing Hormone; Luteinizing Hormone; Male; Neoplasms, Hormone-Dependent; Progestins; Prostatic Neoplasms; Rats; Testosterone

Topics: Animals; Castration; Combined Modality Therapy; Cyclophosphamide; Cyproterone; Dihydrotestosterone; Male; Neoplasm Metastasis; Prostatic Neoplasms; Rats; Testosterone

Standard initial therapy for metastatic prostatic cancer involves surgical or chemically induced castration. Castration lowers the serum testosterone level by over 90% but does not completely eliminate all potential serum androgens (i.e., it induces a partial androgen withdrawal). This has led some investigators to suggest that a more complete form of androgen withdrawal in which the very low levels of serum androgens remaining after castration are neutralized by the simultaneous treatment with a direct acting antiandrogen (i.e., complete androgen withdrawal) might be more effective than simply castration alone. To determine whether complete androgen withdrawal is any more effective than partial androgen withdrawal therapy, the slow growing, well differentiated H and the fast growing, poorly differentiated G sublines of the serially transplantable Dunning R-3327 system of rat prostatic adenocarcinomas were used as a test system since both of these cancers are androgen responsive. These studies demonstrated that: (a) complete androgen withdrawal consisting of surgical castration in combination with daily treatment with the potent antiandrogen, cyproterone acetate, was no more effective in terms of tumor growth retardation or overall host survival than was partial androgen withdrawal induced by castration alone; (b) serum testosterone levels must be maintained below 0.5 ng/ml but do not have to be completely eliminated to produce the maximum therapeutic response; and (c) prostatic cancers are more sensitive than is the normal prostate to growth stimulation by serum testosterone.

Topics: Adenocarcinoma; Animals; Cell Division; Cyproterone; Dihydrotestosterone; Laminin; Male; Microscopy, Electron; Neoplasm Transplantation; Ovariectomy; Prostatic Neoplasms; Rats; Testosterone

Two different hormonal gestagens, cyproterone acetate and norethisterone, were studied in prostatic carcinoma, for the greatest part in advanced cases. Cyproterone acetate was administered to 80, norethisterone to 38 unselected patients. The period of study extended over 2 years or more. The mechanism of action of gestagens and the role of the hormone receptors are discussed. The significance of serial measurements of plasma testosterone by providing a monitor of hormonal therapy is emphasized. The relevant literature is reviewed. The value of gestagens as an alternative to the traditional hormone therapy of prostatic carcinoma is pointed out.

Topics: Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Humans; Male; Norethindrone; Prostatic Neoplasms; Receptors, Cell Surface; Testosterone

The incidence of prostate cancer has recently increased in Japan. Since Huggins demonstrated the dramatic effect of antiandrogenic treatment, patients with prostate cancer are widely treated by bilateral orchiectomy and high dose estrogen. As the incidence of cardiovascular disease has also gradually increased in patients of prostate cancer treated by estrogen in Japan, radiotherapy, radical prostatectomy, antiandrogen such as chlormadinone acetate, cyproterone acetate and anticancer chemotherapy are now sought and tested clinically. The authors have emphasized multidisciplinary treatment according to the stage of prostate cancer. In particular, early prostate cancer without metastasis should be radically treated with radiotherapy or prostatectomy.

Topics: Chlormadinone Acetate; Cyproterone; Cyproterone Acetate; Estrogens; Humans; Male; Prostatectomy; Prostatic Neoplasms; Radiotherapy Dosage

In three groups of patients with advanced prostatic cancer the influence of three different forms of hormonal manipulation, i.e. estrogens, anti-androgens and bilateral orchidectomy, on the coagulation and fibrinolytic systems has been investigated. The groups, studied over a period of 35 days, were comparable as to age and stage of malignancy. A significant decrease in antithrombin III (AT-III) activity of 27% (range 7-46%) was found in patients on an initially high-dose estrogen (diethylstilbestrol) treatment regime. No changes in any of the monitored coagulation and fibrinolytic parameters were noted in the other treatment groups, including patients on maintenance estrogen therapy. The results of this study show that only high-dose estrogen therapy is accompanied by a selective decrease in AT-III activity. This may be an important etiological factor in the increased risk of thromboembolism in patients treated by this regime. The other means of hormonal manipulation studied, including low-dose estrogen treatment, did not influence the coagulation or fibrinolytic systems.

Topics: Aged; Antithrombin III; Castration; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Fibrinolysis; Humans; Male; Middle Aged; Prostatic Neoplasms

Serum concentrations of gonadotropins, testosterone and dehydrotestosterone were determined in patients receiving conventional endocrine therapy for advanced metastatic adenocarcinoma of prostate. The effect over 4 h of a single dose of a long acting analogue of LHRH was determined in these patients and compared to the response in patients receiving the analogues as first choice of treatment. Oestrogen therapy was found to suppress basal and stimulated gonadotropins and testicular androgens. Cyproterone therapy only partially reduced basal hormone concentrations and the response to the LHRH analogue was delayed. Orchidectomy resulted in elevated gonadotropins and an exaggerated response to the analogue. As patients who relapse while failing conventional therapy, may subsequently be treated by further endocrine manipulation, precise determination of their endocrine status should predict any expected benefit. Patients previously treated with stilboestrol are unlikely to respond to orchidectomy or LHRH analogue.

Topics: Adenocarcinoma; Buserelin; Castration; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

Topics: Adenocarcinoma; Aged; Brachytherapy; Cesium Radioisotopes; Cyproterone; Cyproterone Acetate; Estrogens; Gonadotropin-Releasing Hormone; Humans; Iridium; Lymph Node Excision; Male; Middle Aged; Orchiectomy; Prostatectomy; Prostatic Neoplasms; Triptorelin Pamoate

Prostatic adenocarcinomas were induced in 5 out of 20 Wistar rats upon a single administration of 50 mg/kg N-nitroso-N-methylurea (NMU). The rats were pretreated with a daily dose of 50 mg/kg cyproterone acetate for 3 weeks followed by 3 daily injections of 100 mg/kg testosterone. All tumours developed in the dorsolateral prostate and were invasively growing. In 2 cases distant metastases were found. Three proliferative lesions classified as carcinomas in situ were also found in the dorsolateral prostate. A total of 7/20 animals (35%) carried an adenocarcinoma and/or a carcinoma in situ. In addition, 6 epithelial hyperplasias were observed in the dorsolateral and 1 in the ventral prostate of non-tumour-bearing rats. The method described may provide a good animal model for cancer of the prostate and lead to a better understanding of prostatic carcinogenesis.

Topics: Adenocarcinoma; Animals; Carcinoma in Situ; Cocarcinogenesis; Cyproterone; Cyproterone Acetate; Male; Methylnitrosourea; Models, Biological; Neoplasm Metastasis; Neoplasms, Experimental; Nitrosourea Compounds; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testosterone

The peripheral plasma concentrations of testosterone, luteinising hormone (LH) and follicle stimulating hormone (FSH) were determined in 46 patients (age 51-86 years) with cytologically confirmed prostatic carcinoma. Treatment consisted of subcapsular orchidectomy (15 cases) or estrogen medication (16 cases) or cyproterone acetate (15 cases). The determinations were made before and 2 weeks and 2 months after treatment was initiated. No correlation was found between the pretreatment levels of testosterone and gonadotrophins and the local extent of the primary tumor or the degree of malignancy. Nor was there any correlation between hormonal level, presence of metastases or patient age. Orchidectomy and estrogen medication both resulted in very low plasma testosterone levels, corresponding to 15% of the pretreatment values. This proportion was 28% in the group treated with cyproterone acetate. Orchidectomy was followed by significant increase in the levels of LH and FSH. Estrogen treatment resulted in suppression of the LH levels to 40% and of FSH to 14% of the pretreatment values. The corresponding decreases in response to cyproterone acetate were 65 and 35%. The results indicate that reduction in gonadotrophin secretion is the primary mechanism in the lowering of testosterone levels produced by treatment with estrogens or cyproterone acetate.

Topics: Aged; Castration; Cyproterone; Cyproterone Acetate; Estrogens; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testis; Testosterone

The present study has compared the response to antiandrogen therapy of the serially transplantable Dunning R-3327-AT (hereafter called AT) versus Dunning R-3327-G (hereafter called G) rat prostatic adenocarcinoma. Castration or chemical antiandrogen therapy (i.e., cyproterone acetate and diethylstilbestrol) of rats bearing established AT or G tumors results in neither regression of tumor volume nor a cessation of the continuous growth of either tumor. By these criteria, both the AT and G tumors progress following antiandrogen therapy. For the AT tumor, this progression is completely unresponsive to hormonal therapy, and thus such therapy does not increase survival of AT tumor-bearing rats. The AT tumor is therefore an example of hormonally unresponsive progression. In direct contrast, while the G tumor likewise progresses following antiandrogen therapy, this therapy does induce a 1.8-fold decrease in the subsequent growth rate of the G tumor. This positive response during progression of the G tumor results in a 78% increase in the survival of G tumor-bearing rats treated with antiandrogen therapy. The G tumor is therefore an example of hormonally responsive progression. These results indicate neither that prostatic cancers which do not regress or cease growing following antiandrogen therapy can necessarily be considered hormonally unresponsive nor that antiandrogen therapy of such tumors has been completely ineffective, since, as shown in the present study, such progression can be of either a hormonally unresponsive or a responsive type. Regardless of which type of progression occurs, however, additional therapy is required to further increase survival. The present study demonstrates that such additional therapy should probably not include the subsequent use of pharmacological doses of exogenous androgen, since, depending on the type of progression, such treatments can actually decrease survival.

Topics: Adenocarcinoma; Animals; Castration; Cell Division; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Kinetics; Male; Neoplasms, Experimental; Prostatic Neoplasms; Rats

Topics: Castration; Cell Nucleus; Cyproterone; Cyproterone Acetate; Cytosol; Humans; Male; Prostatic Neoplasms; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Receptors, Steroid

THe different modes of treatment of prostate carcinoma, at present determined largely by the stage of the disease, are discussed with reference to the author's patients and to cases described in the literature. Only ca. 10% of cases may be cured. The main types of palliative treatment are those with anti-androgens or with cytostatic drugs. The indiscriminate use of oestrogen therapy should be avoided. The prognosis can be improved only by closer consideration of histology/grading. True progress towards a cure must wait upon advances in basic research.

Topics: Antineoplastic Agents; Castration; Cyproterone; Cyproterone Acetate; Estradiol Congeners; Humans; Male; Neoplasm Staging; Palliative Care; Prognosis; Prostatectomy; Prostatic Neoplasms

Salt and water metabolism was investigated during treatment with oestrogens and with cyproterone acetate and after orchidectomy in 46 patients. An increase in plasma volume was noted during oestrogen treatment and a slight transitory rise in plasma volume was also seen after orchidectomy. During cyproterone acetate therapy there was a reduction of body weight and a transitory increase in 24-hour urine volume and urinary sodium excretion. The increase in plasma volume during oestrogen treatment might tax the circulatory capacity. Cyproterone acetate treatment does not change the salt-water balance or the plasma volume in such a way that the risk of congestive heart failure could be increased.

Topics: Aged; Castration; Cyproterone; Cyproterone Acetate; Estrogens; Humans; Male; Middle Aged; Plasma Volume; Prostatic Neoplasms; Water-Electrolyte Balance

The incidence of thromboembolic complications is increased in patients with oestrogen-treated prostatic carcinoma. Because reduced antithrombin-III (AT-III) levels are associated with increased risk of thromboembolism we have determined AT-III concentrations during oestrogen therapy and other treatments. Forty-six patients with carcinoma of the prostate were allocated to either treatment with subcapsular orchiectomy, oestrogen administration, or cyproterone acetate, AT-III was determined before treatment, at 2 weeks and 2 months later. During oestrogen therapy there was a significant reduction in AT-III to 77% of the base-line value. No significant changes were found after orchiectomy. During cyproterone-acetate treatment there was a slight but significant increase in AT-III at 2 months. The reduction in AT-III could indicate an increased risk of thromboembolism during oestrogen treatment of patients with carcinoma of the prostate. On the other hand, the unchanged AT-III levels after orchiectomy and the increased levels during cyproterone acetate therapy could mean that the risk of thromboembolism is less with these two forms of treatment.

Topics: Aged; Antithrombin III; Castration; Cyproterone; Cyproterone Acetate; Estrogens; Humans; Male; Middle Aged; Prostatic Neoplasms; Thromboembolism

15 patients with advanced carcinoma of the prostate were studied in a prospective trial during treatment with 200 mg cyproterone acetate daily by mouth. Changes in variables (salt-water balance, antithrombin III, fibrinolytic activity, plasma lipoproteins) known to influence the risk of cardiovascular complications were recorded during the initial two months. Blood and plasma volume were unchanged, whereas the 24 h urine volume and the urinary sodium excretion were transitory increased. The body weight was decreased. The antithrombin III concentration and the fibrinolytic activity were increased. The lipoprotein fractions HDL and LDL and the HDL/LDL quotient decreased. The recorded changes of cardiovascular risk factors indicate that the risk of water retention and thereby congestive heart failure is not increased during cyproterone acetate treatment. The risk for thrombembolic disease is rather decreased. The small changes in lipoprotein fractions can hardly affect the incidence of cardiovascular disease in elderly men with prostatic carcinoma.

Topics: Aged; Antithrombin III; Cardiovascular Diseases; Cyproterone; Cyproterone Acetate; Hemodynamics; Humans; Lipoproteins; Male; Middle Aged; Prostatic Neoplasms; Risk; Water-Electrolyte Balance

Five patients with prostatic carcinoma (stages T3N0M0) were injected intramuscularly with 300 mg of cyproterone acetate (CPA) (Androcur-Depot) at weekly intervals. The concentrations of CPA, testosterone, LH, FSH, and prolactin in plasma after the first, third, and fifth injection were measured by specific radioimmunoassays. After five injections of Androcur-Depot, CPA levels were slightly higher than in previous determinations, suggesting that a balance between active substance release from the depot and excretion could be achieved after eight to twelve injections, with only slightly higher levels of active substance attained. Testosterone levels clearly were reduced after the first injection of CPA, but the lowest values were registered only after three injections. Plasma concentrations of FSH and LH were slightly diminished, whereas the prolactin level increased after CPA therapy.

Topics: Cyproterone; Cyproterone Acetate; Follicle Stimulating Hormone; Humans; Injections, Intramuscular; Kinetics; Luteinizing Hormone; Male; Prolactin; Prostatic Neoplasms; Testosterone

Plasma prolactin was measured in 10 patients with prostatic cancer during treatment with cyproterone acetate (300 mg/week i.m.) Prolactin was assayed during a six month period at weekly intervals during the first 4 weeks and then at monthly intervals. Orchiectomy was not carried out. After 6 months prolactin levels were elevated compared with pre-treatment levels. It is concluded from this study that cyproterone acetate interferes with prolactin secretion by the pituitary gland.

Topics: Aged; Cyproterone; Cyproterone Acetate; Humans; Male; Middle Aged; Pituitary Gland; Prolactin; Prostatic Neoplasms; Time Factors

The male predominance in atherosclerotic disease has been ascribed to differences in lipid and lipoprotein metabolism between men and women. The influences of estrogen and antiandrogen treatment on the cholesterol ester metabolism and lipoproteins in plasma in men were therefore studied. Forty-six men with carcinoma of the prostate were studied before and after 2 and 8 weeks' treatment with either polyestradiol phosphate and ethinyl estradiol or orchidectomy or the testosterone receptor-blocking gestagenic drug cyproterone acetate. The estrogen treatment increased the HDL-TC and the level of TGs in HDL and LDL and reduced the TC and LDL-TC simultaneously with elevations of the fractional and molar cholesterol esterification rates. Orchidectomy caused only slight elevations of the TC level and the molar cholesterol esterification rate. Cyproterone acetate reduced the TC, LDL-TC, and HDL-TC concentrations simultaneously with an increase in the fractional cholesterol esterification rate. The alterations of TC and LDL-TC were positively correlated to the changes in the molar cholesterol esterification rate and negatively correlated to the alteration in the fractional cholesterol esterification rate. High doses of estrogen appeared to raise the TG level and the production of CE in plasma. Both estrogen and cyproterone acetate therapy lowered the LDL-TC level simultaneously with a raised fractional elimination of unesterified cholesterol as CEs from plasma. Although the testosterone production was practically eliminated by all three forms of treatment, there was no change of plasma lipoproteins common to all three groups. Therefore the lower estrogen level rather than the higher testosterone level might cause the lower HDL levels in men compared to women.

Topics: Aged; Castration; Cholesterol Esters; Contraceptive Agents, Male; Cyproterone; Cyproterone Acetate; Estradiol; Estradiol Congeners; Ethinyl Estradiol; Humans; Lipoproteins; Male; Middle Aged; Organophosphorus Compounds; Phosphatidylcholine-Sterol O-Acyltransferase; Prostatic Neoplasms

Twenty-six patients with carcinoma of the prostate were allocated to treatment by subcapsular orchidectomy, estrogen administration, or cyproterone acetate administration. Tissue fibrinolytic activity in skin biopsy specimens was estimated by a histochemical method before treatment was initiated and 2 and 8 weeks later. Orchidectomy caused no significant changes in the fibrinolytic activity. During estrogen therapy the fibrinolytic activity in skin was significantly reduced at 8 weeks. In the group given cyproterone acetate the activity was significantly increased at 8 weeks. In the group given cyproterone acetate the activity was significantly increased at 8 weeks. The reduction in fibrinolytic activity in skin could contribute to the increased risk of thromboembolism during estrogen treatment of patients with cancer of the prostate.

Topics: Aged; Castration; Cyproterone; Estrogens; Fibrinolysis; Humans; Male; Middle Aged; Prostatic Neoplasms; Risk; Skin; Thromboembolism; Time Factors

An 80-year-old man with advanced adenocarcinoma of the prostate received cyproterone acetate, 200 mg orally per day as sole treatment. Striking regression of the tumour was demonstrated by ultrasonograms and excretory urograms. Serum concentrations of acid phosphatases, gonadotrophins, and testosterone decreased significantly. No significant cardiovascular side effects occurred.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Cyproterone; Humans; Male; Pituitary Hormones; Prostatic Neoplasms; Radiography; Testosterone

We examined the effects and mechanisms of action of various endocrine manipulations on the epithelium and muscle preparations of the guinea pig seminal vesicle. Castration, which reduced the plasma testosterone level to 10 percent of normal, caused approximately 80 per cent reductions in epithelium wet weight and RNA and DNA contents. Estradiol benzoate effected similar reductions in plasma androgen and epithelial cell function in intact males. Reduction in plasma androgen level accounted for the estrogen-induced epithelial regression; no antiandrogenic effect of estrogen on the epithelium was detectable. All anti-androgens tested, flutamide, spironolactone, and cyproterone acetate, reduced epithelium weight in intact animals. Studies of the mechanism of cyproterone acetate action indicated its effects were attributable solely to an anti-androgenic action on the epithelium. The anti-estrogens, tamoxifen and nafoxidine, had no effect on the epithelium of intact animals when tested alone or in combination with cyproterone acetate. Regression of seminal vesicle muscle occurred only after castration or treatment of intact animals with cyproterone acetate. The action of cyproterone acetate on the muscle was attributable to blockade of the androgenic stimulus. The drug had no effect on plasma testosterone or estradiol levels and had no anti-estrogenic activity. In intact males estradiol reduced plasma testosterone to castrate levels, but did not alter muscle weight and nucleic acid levels. The potential deleterious effects of reduced plasma testosterone on the muscle were surmounted by direct estrogenic stimulation of the tissue. The anti-androgens, flutamide and spironolactone, and the anti-estrogens, tamoxifen and nafoxidine, had no effect on the muscle of intact males. Inasmuch as the regressive effects of castration on the epithelium and muscle can be duplicated in intact animals only by treatment with cyproterone acetate, this particular drug may provide the most effective nonsurgical treatment of prostatic neoplasia.

Topics: Androgen Antagonists; Animals; Castration; Cyproterone; Dihydrotestosterone; Epithelium; Estradiol; Estrogen Antagonists; Guinea Pigs; Male; Muscles; Prostatic Neoplasms; Seminal Vesicles

Occurrence of steroid hormone receptor has been evaluated in 30 prostatic cancer-bearing patients: 5 alpha-dihydrotestosterone receptor (DHTR) occurrence was correlated with both tumor grade of differentiation and clinical response to hormone therapy.

Topics: Aged; Androgen Antagonists; Cyproterone; Dihydrotestosterone; Estradiol; Humans; Hydrocortisone; Male; Middle Aged; Progesterone; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Receptors, Steroid

The treatment of early stage prostatic cancer with retropubic radical prostatectomy, pelvic lymphadenectomy and antiandrogenic therapy is reported. Out of 22 patients operated in the past 9 years, none died because of the tumor and metastases appeared in 1 patient only. The latter showed a microscopic seminal vesicle invasion and was considered as a P3 stage. Excluding impotence which is generally the rule, urinary incontinence was the most common complication: it was complete in 1 case but successfully treated surgically and mild in 6 cases without, however, requiring surgical intervention or collection device.

Topics: Aged; Cyproterone; Cyproterone Acetate; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms

We studied urinary oxalate excretion in three groups of patients with prostatic carcinoma who were treated with orchiectomy, estrogen, and cyproterone acetate, respectively. Urinary oxalate and plasma testosterone were analyzed before treatment and after 2 and 8 weeks of treatment. Despite a decrease in plasma testosterone concentration no significant change in oxalate excretion was detected in any group.

Topics: Aged; Castration; Cyproterone; Cyproterone Acetate; Estradiol; Ethinyl Estradiol; Humans; Male; Middle Aged; Organophosphorus Compounds; Oxalates; Prostatic Neoplasms; Testosterone

Cyproterone acetate was administered orally and intramuscularly to 5 male patients. The level of the active substance in plasma was monitored at intervals during the period of application using radioimmunoassay specific for cyproterone acetate. The areas under the drug level curves were similar after oral and intramuscular application of cyproterone acetate when taking into consideration the different doses used. Accordingly, cyproterone acetate is not dependent upon a "first-pass" effect. The bioavailability of the active substance was complete following oral application.

Topics: Administration, Oral; Aged; Biological Availability; Cyproterone; Cyproterone Acetate; Humans; Injections, Intramuscular; Male; Middle Aged; Prostatic Neoplasms; Radioimmunoassay

Two of 33 prostatic tumour xenografts were established and passaged. Testosterone supplementation did not improve tumour take rates. The histological grade of the parent tumour was the principal factor affecting xenograft survival. Preliminary studies on established tumour xenografts suggest that their value lies in the study of tumour biology, and that they have no direct therapeutic application at present.

Topics: Animals; Arginase; Cyproterone; Estradiol; Female; Graft Survival; Humans; Male; Mice; Mice, Inbred CBA; Mice, Nude; Neoplasm Transplantation; Neoplasms, Experimental; Prostatic Neoplasms; Testosterone; Transplantation, Heterologous

Cyproterone acetate was given to patients with stages C and D prostatic cancer and its effect on endocrine parameters was studied. At a daily oral dose of 100 mg. cyproterone acetate induced marked reduction in the size and consistency of tumor, while it caused moderate suppression of serum luteinizing hormone, follicle-stimulating hormone and testosterone levels. Elevation of serum prolactin levels was observed after treatment with cyproterone acetate but was to a lesser degree than that caused by estrogens.

Topics: Aged; Cyproterone; Follicle Stimulating Hormone; Gonadotropins, Pituitary; Humans; Luteinizing Hormone; Male; Middle Aged; Prolactin; Prostatic Neoplasms; Testosterone

We report the results from 106 patients with extracapsular (stage C) or widespread (stage D) prostatic cancer, who were treated with cyproterone acetate and orchiectomy and followed for 5 years. As controls we used 40 patients, chosen at random, with stage C and stage D cancer of the prostate gland who were treated with stilbestrol and orchiectomy. The survival rate is improved in patients treated with cyproterone acetate and orchiectomy compared to the patients treated with stilbestrol and orchiectomy. Treatment with cyproterone seems more effective in those patients with low-stage and low-grade prostatic cancer. The side effects of this therapy are less and milder than those described in estrogenic treatment alone or with orchiectomy.

Topics: Adult; Aged; Carcinoma; Castration; Cyproterone; Diethylstilbestrol; Follow-Up Studies; Humans; Italy; Male; Middle Aged; Prostatic Neoplasms

We have studied 38 patients with previously untreated, widespread prostatic cancer, who were submitted to therapy with cyproterone acetate and orchiectomy. 70% of patients with symptoms have shown subjective improvement. Moreover, it was possible to observe the regression, stabilization or progression of metastases in 32, 50 and 18% of the cases, respectively. We conclude that such therapy is effective in the initial treatment of metastatic prostate cancer and can be continued under radiographic control until the appearance of new metastases. At this point radiotherapy and alkylating agents may be effective.

Topics: Adult; Aged; Carcinoma; Castration; Cyproterone; Humans; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Prostatic Neoplasms; Radiography

The incidence of cardiovascular disease is lower in women than in men, but is raised in men with prostatic cancer treated by estrogens. The antiandrogenic gestagenic drug, cyproterone acetate, is sometimes used instead of estrogens in the treatment of prostatic cancer. The cardiovascular risk associated with such hormonal treatment has been debated. Changes in plasma lipoproteins are related to the risk of cardiovascular disease and can be brought about by hormonal treatment. Plasma lipoproteins were therefore investigated during cyproterone acetate therapy in 15 men with prostatic cancer. Cholesterol (C), triglyceride, and phospolipid (PL) concentrations were determined in the very low density, low density (LDL), and high density lipoprotein (HDL) fractions. During treatment, mean body weight decreased by 1.2 and 1.9 kg after 2 and 8 weeks, respectively. The mean C concentration was lowered by 16%. The HDL C was reduced by a mean of 25%, and the LDL C decreased by means of 15% and 10%. The part of plasma C carried in the HDL fraction decreased slightly from 19 to 17% (mean) and the mean HDL C/LDL c quotient was lowered from 0.27 to 0.22. The mean PL concentration in plasma was decreased due to a mean reduction of HDL-PL by 17% and LDL Pl by 10%. A reduction of the HDL/LDL quotient implicates an increased risk for development of atherosclerotic diseases. However, it seems unlikely that a modest reduction in the HDL/LDL quotient, as obtained by cyproterone acetate, should have any great influence on the incidence of cardiovascular disease in elderly men with prostatic carcinoma.

Topics: Aged; Cholesterol; Cyproterone; Humans; Lipoproteins; Lipoproteins, HDL; Lipoproteins, LDL; Lipoproteins, VLDL; Male; Middle Aged; Phospholipids; Prostatic Neoplasms; Triglycerides

Topics: Adenocarcinoma; Bone Neoplasms; Cyproterone; Humans; Male; Middle Aged; Prostatic Neoplasms

Topics: Cyproterone; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

The criteria for the diagnosis of progression of prostatic cancer after primary treatment by androgen suppression (oestrogen escape) were studied in 30 patients. Objective criteria are essential for this diagnosis and in this study the bone scan was the most useful criterion. Twenty-one of these patients had a secondary orchiectomy: one patient showed a partial objective response and 3 had a subjective response. It is concluded that an orchiectomy following failed primary oestrogen therapy is an ineffective procedure and therefore unjustifiable and that alternative treatments must continue to be evaluated.

Topics: Aged; Castration; Cyproterone; Estradiol Congeners; Humans; Male; Middle Aged; Prostatic Neoplasms

Early stage carcinoma of the prostate is curable. Not every patient must be treated because there are significant differences in the biologic activity of the tumors. This causes a sharp difference between morbidity and mortality rate in prostatic cancer. Besides the clinical staging morphological malignancy grading is the trend factor for the treatment that has to be chosen because it has shown to be a reasonable and feasable prognostic indicator.

Topics: Adrenalectomy; Androgen Antagonists; Antineoplastic Agents; Cordotomy; Cyproterone; Estrogens; Humans; Hypophysectomy; Lymph Node Excision; Male; Neoplasm Metastasis; Neoplasm Staging; Palliative Care; Pelvis; Prognosis; Prostatectomy; Prostatic Neoplasms

An immunocytochemical technique was described to test for immunoreactive prolactin (PRL) and growth hormone (GH) in spontaneous and experimentally induced hyperplastic and neoplastic lesions of the prostate and mammary gland. The dog was used as an animal model. The specificity and validity of the immunocytochemical staining procedure and of the antisera to canine PRL and canine GH can be regarded as established for the demonstration of PRL- and GH-dependent staining respectively. In mammary and prostatic tissues, both endogenous PRL and GH as well as intracellular free binding sites (for exogenous PRL and GH) were detected immunocytochemically. The technique presented seems to be an important tool to localize putative target sites for pituitary hormones in hormone-dependent hyperplasia and neoplasia.

Topics: Androstenediol; Animals; Castration; Cyproterone; Dogs; Estradiol; Female; Growth Hormone; Immunoenzyme Techniques; Male; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Prolactin; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms

A new procedure has been developed to purify prostatic cell nuclei and to achieve a high yield of nuclear material for study. This technique allowed the investigation of the enzyme 5-alpha-reductase and its relationship to the translocation of dihydrotestosterone and androgen receptors into the nucleus of the prostatic cell. The studies revealed that 5-alpha-reductase was localized chiefly to the stromal components of all types of prostatic tissue. Although there is a higher concentration of dihydrotestosterone in carcinoma tissue the 5-alpha-reductase activity is low. Studies on the effect of androgens and antiandrogens on nuclear uptake of androgen revealed that androgens are potent stimulants of receptor translocation, while antiandrogens stimulate little or no translocation.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Androgen Antagonists; Animals; Cyproterone; Dihydrotestosterone; Estrenes; Flutamide; Humans; Male; Prostatic Hyperplasia; Prostatic Neoplasms; Rats; Receptors, Androgen; Receptors, Steroid

Since prostatic carcionma is hormone dependent, treatment of this tumor has been carried out in this department over the last 10 years employing antiandrogens, particularly cyproterone acetate (CPA), associated in some cases with orchiectomy. Of 500 patients thus treated, the author reports on 236 patients with a 5-year follow-up and 184 with a 7-year follow-up. Of these, 126 (53.4%) had not received hormone treatment whereas 110 (46.6%) had been treated with estrogens. The mean survival rate was 64.4% at 5 years and 56.3% at 7 years in these patients and 51 and 43%, respectively, in the estrogen-treated patients. The author emphasizes that not only is CPA of great value in the treatment of prostatic carcinoma, but it is also useful in determining the hormone dependency of the tumor which is indispensable before proceeding with hormone therapy.

Topics: Adenocarcinoma; Castration; Cyproterone; Drug Evaluation; Follow-Up Studies; Humans; Male; Prostatic Neoplasms

Cyproterone acetate, an antiandrogen drug, is used to reduce mammalian fertility. Effects on the human testis are controversial. Findings in this study reveal that long-term treatment-7 months with 200 mg/day-leads to disappearance of the germinal cells and to Sertoli cells with either a normal or undifferentiated aspect as well as involution of the Leydig cell. Some pathogenetic hypotheses on the action of cyproterone acetate upon human spermatogenesis are discussed.

Topics: Cyproterone; Humans; Leydig Cells; Male; Middle Aged; Prostatic Neoplasms; Sertoli Cells; Testis

Sixteen patients with prostatic carcinoma were treated with 200 mg of Cyproterone acetate daily. No other kind of hormonal treatment was given. Transrectal biopsies of the prostate were taken before the treatment was started, and at regular intervals afterwards. The treatment period lasted from 3 to 16 months, with an average of 9 months. A thorough examination of multiple sections from all specimens revealed no convincing signs of cellular involution. The study has demonstrated no specific or significant atrophic changes following Cyproterone acetate therapy. Some possible explanations regarding the effect of Cyproterone acetate on human malignant prostatic tissue are discussed.

Topics: Adenocarcinoma; Aged; Atrophy; Biopsy; Carcinoma; Cyproterone; Humans; Male; Middle Aged; Prostate; Prostatic Neoplasms

Sixteen patients with prostatic carcinoma were treated with 200 mg of Cyproterone acetate daily. No other kind of hormonal treatment was administered. Increasing skeletal metastases were observed in 6 patients, whereas significant reduction of metastases took place in 2 patients. Objective relief of stranguria was observed only in 3 patients. The amount of residual urine increased in 3 patients and was reduced in 5. In about one third of the patients, the prostate gland became smaller and softer. The acidic phosphatases decreased from pathological to normal values in 7 patients. There were no observed hepatic, renal or haemotological side-effects. However, serious cardio-vascular complications occurred in 6 patients, while arterial hypertension developed in 4. It is suggested that Cyproterone acetate cannot be recommended as the only kind of hormonal treatment of prostatic cancer.

Topics: Acid Phosphatase; Administration, Oral; Aged; Blood Pressure; Bone Neoplasms; Cyproterone; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Urination

Topics: Androgen Antagonists; Castration; Cryosurgery; Cyproterone; Humans; Immunoglobulin M; Male; Prostatic Neoplasms

Topics: Cyproterone; Drug Tolerance; Humans; Male; Prostatic Neoplasms

Topics: Cortisone; Cyproterone; Estrogens; Humans; Male; Methods; Prostatic Neoplasms

Ureteral obstruction occurred in 10% of the patients treated for prostatic carcinoma and most often was associated with poorly differentiated tumors. The response of ureteral obstruction to different forms of therapy was evaluated. Obstruction diminished in 22 of 25 orchiectomized patients (88%) but in only 1 of 6 patients receiving estrogen or antiandrogen therapy alone (17%). Patients who responded favorably to therapy had a significantly better survival than did non-responders. Patients treated early in the course of ureteral obstruction responded better than those treated late, while neither tumor stage nor grade correlated with response to therapy. Radiation therapy for endocrine-resistant ureteral obstruction was effective in only 2 of 8 cases (25%). The literature on ureteral obstruction from prostatic carcinoma and its treatment is reviewed.

Topics: Acid Phosphatase; Androgen Antagonists; Castration; Cyproterone; Diethylstilbestrol; Estrogens; Humans; Male; Maryland; Prostatic Neoplasms; Remission, Spontaneous; Time Factors; Ureteral Obstruction

Topics: Adult; Child; Cyproterone; Drug Evaluation; Female; Humans; Libido; Male; Paraphilic Disorders; Prostatic Neoplasms; Puberty, Precocious; Virilism

Topics: Androgen Antagonists; Animals; Cyproterone; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Male; Organ Size; Prostate; Prostatic Hyperplasia; Prostatic Neoplasms; Testosterone; Transplantation, Heterologous

Topics: Cyproterone; Humans; Male; Middle Aged; Neoplasm Metastasis; Penile Neoplasms; Prostatic Neoplasms

Topics: Adrenalectomy; Androgen Antagonists; Androgens; Animals; Castration; Chemical Phenomena; Chemistry; Chlormadinone Acetate; Cyproterone; Depression, Chemical; Dihydrotestosterone; Estrogens; Hormones; Humans; Hypophysectomy; Luteinizing Hormone; Male; Prostate; Prostatic Neoplasms; Testosterone

Topics: Adenoma; Androstane-3,17-diol; Cyproterone; Dihydrotestosterone; Gestonorone Caproate; Humans; Male; Muscles; Progesterone; Prostate; Prostatic Neoplasms; Testosterone

Topics: Acne Vulgaris; Androgen Antagonists; Animals; Cyproterone; Dermatitis, Seborrheic; Estrenes; Female; Fetus; Growth; Humans; Male; Mice; Pregnancy; Progesterone; Prostatic Neoplasms; Rats; Spermatogenesis; Testis; Testosterone

Topics: Androgens; Animals; Cyproterone; Dihydrotestosterone; Dogs; Estradiol; Humans; Male; Prostate; Prostatic Neoplasms; Testosterone; Tritium

Topics: Chlorambucil; Choriocarcinoma; Cyproterone; Dactinomycin; Estrogens; Humans; Lymph Node Excision; Male; Penile Neoplasms; Prostatic Neoplasms; Testicular Neoplasms; Urogenital Neoplasms

Topics: 17-Ketosteroids; Aged; Alkaline Phosphatase; Androgen Antagonists; Carcinoma; Cyproterone; Humans; Hydroxysteroids; Male; Middle Aged; Pain; Pregnadienes; Prostatic Neoplasms

Topics: Acid Phosphatase; Alkaline Phosphatase; Androgen Antagonists; Animals; Castration; Chlorides; Cyproterone; Depression, Chemical; Diethylstilbestrol; Dogs; Glucose; Male; Osmolar Concentration; Potassium; Pregnadienes; Prostate; Prostatic Neoplasms; Proteins; Secretory Rate; Sodium; Testosterone

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Androgen Antagonists; Bone Neoplasms; Carcinoma; Cyproterone; Estrogens; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pregnadienes; Prostatic Neoplasms

Topics: Adenocarcinoma; Antineoplastic Agents; Cyproterone; Drug Therapy, Combination; Endometriosis; Estrogens; Female; Humans; Kidney Neoplasms; Male; Prednisone; Progestins; Prostatic Neoplasms; Uterine Neoplasms

Topics: Androgen Antagonists; Animals; Arginase; Body Weight; Castration; Cyclophosphamide; Cyproterone; Disease Models, Animal; DNA; Dogs; Drug Evaluation, Preclinical; Fluorouracil; Humans; Male; Organ Size; Oxidoreductases; Prostate; Prostatic Neoplasms; Rats

Topics: Bone Neoplasms; Castration; Cyproterone; Estrogens; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Neoplasm Metastasis; Prostatic Neoplasms; Spinal Cord Neoplasms

Topics: Adult; Aged; Androgen Antagonists; Body Weight; Cyproterone; Diet; Dose-Response Relationship, Drug; Ethinyl Estradiol; Female; Hirsutism; Humans; Male; Menstruation Disturbances; Middle Aged; Nitrogen; Pregnadienes; Prostatic Neoplasms