goserelin and Prostatic-Neoplasms

Androgen deprivation therapy (ADT) using gonadotropin-releasing hormone agonist (s) (GnRH-A) remains the backbone of advanced prostate cancer treatment. In this review, we assessed the efficacy, safety, and convenience of administration of various GnRH-A. All GnRH-A (goserelin, triptorelin, buserelin, histrelin, and leuprorelin) have comparable potential to suppress testosterone (T) levels (≤50 ng/dL in a month and ≤20 ng/dL in 3 months). However, goserelin has shown better efficacy in maintaining T levels ≤50 ng/dL compared with leuprolide. The incidences of T escape are lower with goserelin and leuprolide than buserelin. Goserelin also has maximum benefit in prostate-specific antigen suppression. In neoadjuvant setting, when only goserelin was used, the 10-year overall survival (OS) rate was 42.6% to 86%. When either goserelin or leuprolide was used, the 10-year OS rate was 62%. As an adjuvant to radical prostatectomy, goserelin had a 10-year survival rate of 87%, and triptorelin had an 8-year survival rate of 84.6%. Goserelin further showed an absolute survival rate of 49% when used as an adjuvant to radiotherapy. The survival rates further improved when GnRH-A are used as combined androgen blockade compared with monotherapy. The frequency and severity of adverse events (hot flushes, fatigue, sexual dysfunction) are comparable among the GnRH-A. Goserelin appears to be the most convenient of all the GnRH-A for administration. Lack of conclusive comparative evidence makes it imperative to have a holistic approach of considering the patient profile and the disease characteristics to select the appropriate GnRH-A for ADT in prostate cancer.

Topics: Androgen Antagonists; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms

To review direct comparative studies of the gonadotrophin-releasing hormone (GnRH) agonists goserelin, triptorelin, and leuprorelin for the treatment of prostate cancer, and identify whether there are meaningful clinical differences between these agents. In June 2017, the following searches were performed independently by two reviewers in PubMed: (i) 'prostate cancer' and 'triptorelin' and 'leuprorelin', (ii) 'prostate cancer' and 'triptorelin' and 'goserelin', and (iii) 'prostate cancer' and 'goserelin' and 'leuprorelin', without time restriction. Duplicates were deleted. Relevant conference abstracts were also screened. A total of 16 direct comparative trials were identified: 12 reported on efficacy outcomes, four on safety/tolerability, and five on the convenience of administration/user perceptions. These studies are restricted in terms of patient numbers, formulations assessed, and endpoints measured; none were adequately powered for survival outcome measures. Studies reporting on efficacy endpoints did not show major differences in the ability of these GnRH agonists to reduce levels of testosterone or prostate-specific antigen. Some studies suggest differences in short- or long-term testosterone control, the rate of injection site adverse events, and patient/healthcare professional perceptions, but definitive conclusions cannot be drawn from the existing evidence. Few direct comparative trials of GnRH agonists have been conducted. Whilst GnRH agonists provide a similar castration effect, there is not enough evidence to show that GnRH agonists are equivalent.

Topics: Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Survival Rate; Testosterone; Treatment Outcome; Triptorelin Pamoate

To evaluate the effectiveness and harms of DES in treating prostate cancer compared to other forms of androgen deprivation therapy (orchiectomy, LHRH agonists, and anti-androgens).. We included clinical trials comparing DES with other forms of ADT (bicalutamide, flutamide, LHRH agonists, or orchiectomy) in PCa treatment. The primary outcomes were overall survival, cancer-specific survival, and progression-free survival, and secondary outcomes were cardiovascular effects. We searched in MEDLINE, EMBASE, Central, and Lilacs from inception to nowadays and saturated information for unpublished data in other sources. We performed a qualitative analysis of all included studies. It was not possible to perform meta-analysis due to low-quality trials and high heterogeneity.. Overall, 1700 references were scanned and 14 prospective randomized trials with a total of 3986 patients were included in the final analysis. Although trials showed DES as similarly effective to another forms of ADT, evidences about cardiovascular toxicity in out of date high doses have discouraged its use. In doses of 1 mg, DES has been used as secondary line PCa treatment with safety.. DES might be similarly effective to other forms of ADT on advanced PCa patients, with potential important roles. Intriguingly, the burden of severe cardiovascular toxicity is mainly related to old-fashioned doses of 5.0 and 3.0 mg. Modern PCa hormonal knowledge warrants stout high-quality prospective randomized trials in the low-dose 1 mg DES scenario.

Topics: Anilides; Antineoplastic Agents, Hormonal; Diethylstilbestrol; Estrogens, Non-Steroidal; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Nitriles; Orchiectomy; Prostatic Neoplasms; Tosyl Compounds

The combined use of androgen deprivation therapy (ADT) and image-guided radiotherapy (IGRT) can improve overall survival in aggressive, localized prostate cancer. However, owing to the adverse effects of prolonged ADT, it is imperative to identify the patients who would benefit from this combined-modality therapy relative to the use of IGRT alone. Opportunities exist for more personalized approaches in treating aggressive, locally advanced prostate cancer. Biomarkers--such as disseminated tumour cells, circulating tumour cells, genomic signatures and molecular imaging techniques--could identify the patients who are at greatest risk for systemic metastases and who would benefit from the addition of systemic ADT. By contrast, when biomarkers of systemic disease are not present, treatment could proceed using local IGRT alone. The choice of drug, treatment duration and timing of ADT relative to IGRT could be predicated on these personalized approaches to prostate cancer medicine. These novel treatment intensification and reduction strategies could result in improved prostate-cancer-specific survival and overall survival, without incurring the added expense of metabolic syndrome and other adverse effects of ADT in all patients.

Topics: Androgen Antagonists; Androstenes; Benzamides; Biomarkers; Combined Modality Therapy; Dose-Response Relationship, Radiation; Flutamide; Goserelin; Humans; Male; Neoplasm Recurrence, Local; Nitriles; Phenylthiohydantoin; Prostatic Neoplasms; Radiotherapy, Image-Guided; Risk Assessment; Treatment Outcome

Studies comparing the gonadotropin-releasing hormone antagonist, degarelix, with luteinising hormone-releasing hormone (LHRH) agonists indicate differences in outcomes.. To assess differences in efficacy and safety outcomes in a pooled analysis of trials comparing degarelix with LHRH agonists.. Data were pooled from five prospective, phase 3 or 3b randomised trials (n=1925) of degarelix and leuprolide or goserelin in men requiring androgen deprivation therapy for the treatment of prostate cancer. Patients received either 3 mo (n=467) or 12 mo (n=1458) of treatment.. Men were randomised to receive degarelix (n=1266), leuprolide (n=201), or goserelin (n=458).. Unadjusted Kaplan-Meier analyses were supported by the Cox proportional hazards model, adjusted for disease-related baseline factors, to estimate hazard ratios (HRs) of efficacy and safety outcomes. The Fisher exact test compared crude incidences of adverse events.. Prostate-specific antigen (PSA) progression-free survival (PFS) was improved in the degarelix group (HR: 0.71; p=0.017). For patients with baseline PSA levels >20 ng/ml, the HR for PSA PFS was 0.74 (p=0.052). Overall survival (OS) was higher in the degarelix group (HR: 0.47; p=0.023). OS was particularly improved with degarelix in patients with baseline testosterone levels >2 ng/ml (HR: 0.36; p=0.006). In terms of disease-related adverse events, there were, overall, fewer joint-related signs and symptoms, musculoskeletal events, and urinary tract events in the degarelix group.. These data indicate clinical benefits with degarelix, including a significant improvement in PSA PFS and OS, as well as reduced incidence of joint, musculoskeletal, and urinary tract adverse events, compared with LHRH agonists.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Clinical Trials, Phase III as Topic; Disease-Free Survival; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Oligopeptides; Prostate-Specific Antigen; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate; Testosterone; Treatment Outcome

We performed a systematic review and meta-analysis to assess the efficacy and tolerability of degarelix for lower urinary tract symptom relief, prostate volume reduction and quality of life improvement in men with prostate cancer (PCa).. A literature review was performed to identify all of the published randomized controlled trials (RCTs) that used degarelix versus gonadotropin-releasing hormone agonists plus antiandrogens therapy for the treatment of PCa. The search included the following databases: MEDLINE, EMBASE and the Cochrane Controlled Trials Register.. Three publications involving a total of 466 patients were used in the analysis, including three RCTs that compared degarelix with goserelin plus bicalutamide therapy for PCa over 12 weeks. For the comparison of degarelix with goserelin plus bicalutamide therapy, International Prostate Symptom Score (IPSS) reduction (standardized mean difference [SMD] = -1.85, 95% confidence interval [CI] = -2.97 to -0.72, p = 0.001) and IPSS ≥13 (SMD = -2.68, 95% CI = -4.57 to -0.78, p = 0.006) indicated that decreases in IPSS were greater in degarelix-treated patients than in goserelin plus bicalutamide-treated patients.. Our meta-analysis indicates that, compared with goserelin plus bicalutamide, degarelix has significantly more pronounced effects on lower urinary tract symptoms.

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Chi-Square Distribution; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lower Urinary Tract Symptoms; Male; Nitriles; Odds Ratio; Oligopeptides; Prostatic Neoplasms; Quality of Life; Time Factors; Tosyl Compounds; Treatment Outcome; Tumor Burden

Non-steroidal antiandrogens and castration are the main therapy options for advanced stages of prostate cancer. However, debate regarding the value of these treatment options continues.. To assess the effects of non-steroidal antiandrogen monotherapy compared with luteinising hormone-releasing hormone agonists or surgical castration monotherapy for treating advanced stages of prostate cancer.. We searched the Cochrane Prostatic Diseases and Urologic Cancers Group Specialized Register (PROSTATE), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science with Conference Proceedings, three trial registries and abstracts from three major conferences to 23 December 2013, together with reference lists, and contacted selected experts in the field and manufacturers.. We included randomised controlled trials comparing non-steroidal antiandrogen monotherapy with medical or surgical castration monotherapy for men in advanced stages of prostate cancer.. One review author screened all titles and abstracts; only citations that were clearly irrelevant were excluded at this stage. Then, two review authors independently examined full-text reports, identified relevant studies, assessed the eligibility of studies for inclusion, assessed trial quality and extracted data. We contacted the study authors to request additional information. We used Review Manager 5 for data synthesis and used the fixed-effect model for heterogeneity less than 50%; we used the random-effects model for substantial or considerable heterogeneity.. Eleven studies involving 3060 randomly assigned participants were included in this review. The quality of evidence is hampered by risk of bias. Use of non-steroidal antiandrogens decreased overall survival (hazard ratio (HR) 1.24, 95% confidence interval (CI) 1.05 to 1.48, six studies, 2712 participants) and increased clinical progression (one year: risk ratio (RR) 1.25, 95% CI 1.08 to 1.45, five studies, 2067 participants; 70 weeks: RR 1.26, 95% CI 1.08 to 1.45, six studies, 2373 participants; two years: RR 1.14, 95% CI 1.04 to 1.25, three studies, 1336 participants), as well as treatment failure (one year: RR 1.19, 95% CI 1.02 to 1.38, four studies, 1539 participants; 70 weeks: RR 1.27, 95% CI 1.05 to 1.52, five studies, 1845 participants; two years: RR 1.14, 95% CI 1.05 to 1.24, two studies, 808 participants), compared with medical or surgical castration. The quality of evidence for overall survival, clinical progression and treatment failure was rated as moderate according to GRADE. Predefined subgroup analyses showed that use of non-steroidal antiandrogens, compared with castration, was less favourable for overall survival, clinical progression (at one year, 70 weeks, two years) and treatment failure (at one year, 70 weeks, two years) in men with metastatic disease. Use of non-steroidal antiandrogens also increased the risk for treatment discontinuation due to adverse events (RR 1.82, 95% CI 1.13 to 2.94, eight studies, 1559 participants), including events such as breast pain (RR 22.97, 95% CI 14.79 to 35.67, eight studies, 2670 participants), gynaecomastia (RR 8.43, 95% CI 3.19 to 22.28, nine studies, 2774 participants) and asthenia (RR 1.77, 95% CI 1.36 to 2.31, five studies, 2073 participants). The risk of other adverse events, such as hot flashes (RR 0.23, 95% CI 0.19 to 0.27, nine studies, 2774 participants), haemorrhage (RR 0.07, 95% CI 0.01 to 0.54, two studies, 546 participants), nocturia (RR 0.38, 95% CI 0.20 to 0.69, one study, 480 participants), fatigue (RR 0.52, 95% CI 0.31 to 0.88, one study, 51 participants), loss of sexual interest (RR 0.50, 95% CI 0.30 to 0.83, one study, 51 participants) and urinary frequency (RR 0.22, 95% CI 0.11 to 0.47, one study, 480 participants) was decreased when non-steroidal antiandrogens were used. The quality of evidence for breast pain, gynaecomastia and hot flashes was rated as moderate according to GRADE. The effects of non-steroidal antiandrogens on cancer-specific survival and biochemical progression. Currently available evidence suggests that use of non-steroidal antiandrogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival, clinical progression, treatment failure and treatment discontinuation due to adverse events. Evidence quality was rated as moderate according to GRADE. Further research is likely to have an important impact on results for patients with advanced but non-metastatic prostate cancer treated with non-steroidal antiandrogen monotherapy. However, we believe that research is likely not necessary on non-steroidal antiandrogen monotherapy for men with metastatic prostate cancer. Only high-quality, randomised controlled trials with long-term follow-up should be conducted. If further research is planned to investigate biochemical progression, studies with standardised follow-up schedules using measurements of prostate-specific antigen based on current guidelines should be conducted.

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Disease Progression; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Medication Adherence; Nitriles; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Tosyl Compounds; Triptorelin Pamoate

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

Bone-targeted treatments with bisphosphonates and denosumab, which reduce bone resorption, are known to reduce the risk of skeletal complications and prevent treatment-induced bone loss in patients with malignant bone disease. Additionally, these drugs may modify the course of bone destruction via inhibitory effects on the "vicious cycle" of growth factor and cytokine signaling between tumor and bone cells within the bone marrow microenvironment. Effects of the drugs on the stem cell niche, direct effects on the cancer cells, and immune modulation may also contribute. In early-stage (stages I, II, and III) breast cancer, treatment with the bisphosphonate zoledronic acid has shown improvements in disease-free and overall survival. Improved survival was particularly notable in women with established menopause at diagnosis and in premenopausal women with endocrine-responsive disease who received treatment with goserelin, which suppresses ovarian function by inhibiting the production of ovarian hormones. Additionally, in castrate-resistant prostate cancer, treatment with denosumab delays the development of bone metastases. These results strongly support the adjuvant use of bone-targeted treatments but suggest that reproductive hormones are an important treatment modifier to take into account. In advanced-stage (stage IV, ie, metastatic) cancers, survival benefits have been observed in patients with multiple myeloma and in patients with other solid tumors with rapid rates of bone destruction who received treatment with zoledronic acid. Here, we have critically reviewed the increasing evidence to support a disease-modifying effect of bone-targeted treatment and discussed the impact on clinical management.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Denosumab; Diphosphonates; Disease Progression; Disease-Free Survival; Female; Goserelin; Humans; Imidazoles; Male; Menopause; Neoplasms; Prostatic Neoplasms; Survival Rate; Treatment Outcome; Zoledronic Acid

Luteinizing hormone-releasing hormone (LHRH) agonists represent one of the main cost factors in the management of patients with metastatic prostate cancer. We compared the cost-effectiveness of the five different 3-month formulations of LHRH agonists currently available for advanced prostate cancer in Italy, because these differ both in their capacity to suppress testosterone and in their acquisition costs.. A probabilistic, patient-level simulation model was developed to compare the cost-effectiveness, from the perspective of the Italian National Health Service (INHS), of leuprorelin 11.25 mg and 22.5 mg, triptorelin 11.25 mg, buserelin 9.9 mg, and goserelin 10.8 mg. The model incorporated testosterone-dependent progression-free and cancer-specific survival functions, LHRH agonist effectiveness data, and national costs and tariffs. Cox's proportional hazard models were used to compute total and progression-free survival functions based on clinical data from 129 patients with metastatic prostate cancer treated in an Italian center. Bayesian random effects models were employed to summarize evidence from published literature on testosterone suppression obtained with the available LHRH agonists.. Estimated total survival was ≈5 years, with a maximum difference between treatment options of ≈2 months. There was a mean difference of almost €2,500 in lifetime total costs between the least costly option (leuprorelin 22.5 mg) and the most expensive (goserelin). In the incremental cost-effectiveness analysis, leuprorelin 22.5 mg dominated all alternatives except buserelin, which had an incremental cost-effectiveness ratio versus leuprorelin 22.5 mg of ≈€12,000 per life-month gained.. Based on modelling with meta-analysis of comparative survival data, leuprorelin 22.5 mg was the most cost-effective treatment of the available depot formulation LHRH agonists.

Topics: Aged; Antineoplastic Agents, Hormonal; Buserelin; Cost-Benefit Analysis; Decision Trees; Drug Costs; Gonadotropin-Releasing Hormone; Goserelin; Humans; Italy; Leuprolide; Male; Models, Econometric; Proportional Hazards Models; Prostatic Neoplasms; Survival Analysis; Triptorelin Pamoate

Topics: Aged; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Granuloma; Humans; Injections, Subcutaneous; Male; Microscopy, Electron, Transmission; Prostatic Neoplasms; Skin Diseases

We report a case history of a patient with Parkinson's disease (PD) treated with androgen deprivation therapy (ADT) and external beam radiation for prostate cancer, who developed severe deterioration of his PD during ADT.

Topics: Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Middle Aged; Parkinson Disease; Prostatic Neoplasms

Historically, adjuvant androgen deprivation therapy has been viewed as a palliative treatment option for patients with poor-prognosis non-metastatic prostate cancer. In addition, guidelines from bodies such as the European Association of Urology and American Society for Clinical Oncology do not specifically categorize adjuvant hormonal therapy as being curative in intent. We propose that adjuvant androgen deprivation therapy should now be classified as a treatment of curative intent in patients with poor-prognosis, non-metastatic prostate cancer. By applying a carefully considered definition of cure (based on long-term (10- to 15-year) disease-free survival curves) to the findings from randomized controlled clinical trials that have studied adjuvant hormonal treatments in non-metastatic prostate cancer, we challenged whether this viewpoint should now be considered redundant. According to our review of relevant studies and our definition of cure, goserelin appears to augment cure in a sizeable proportion of men with poor-prognosis non-metastatic prostate cancer when given adjuvant to radical prostatectomy or radiotherapy. Across several trials, the relevant survival curves for the goserelin-treated population became indefinitely flat after long-term follow-up. This indicates that these patients have a mortality risk comparable to the general population without prostate cancer. On the basis of the evidence presented within this review, we believe that, given it can control disease for a long period of time, adjuvant goserelin should be reclassified as a treatment of curative intent for patients with poor-prognosis non-metastatic prostate cancer.

Topics: Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Prognosis; Prostatic Neoplasms

Improvements in longer-term survival rates have been demonstrated for locally advanced prostate cancer patients treated with adjuvant androgen deprivation therapy (ADT), and in subsets of men with clinically localized disease treated with ADT combined with external-beam radiotherapy (RT). In these studies, ADT was administered in the form of surgery (orchiectomy) or with a class of drugs called luteinizing hormone-releasing hormone agonists. Goserelin acetate is a member of this class, and 10 of 11 major Phase III trials demonstrating better outcomes with ADT and RT used goserelin acetate. The reduction in deaths from prostate cancer noted in the mid-1990s may largely be due to the early use of these agents in men with intermediate-to-high-risk disease.

Topics: Antineoplastic Agents, Hormonal; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Goserelin; Humans; Male; Prostatic Neoplasms; Radiotherapy

Topics: Androgen Antagonists; Biopsy, Needle; Castration; Diagnostic Imaging; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prognosis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy; Testosterone

Following the studies of Huggins and colleagues in 1941, the hormonal treatment of prostatic cancer has been aimed at neutralizing the influence of testicular androgens through surgical castration or the administration of high dose estrogen. Labrie et al introduced combined use of a LHRH agonist and an androgen antagonist for prostatic cancer. Various reports demonstrated a beneficial effect for combined androgen blockade using nonsteroidal antiandrogens for advanced prostatic cancer through meta-analysis of published randomized control trials. In Japanese status, a combined androgen blockade is popular for advanced prostatic cancer as well as local cancer by J-Cap survey. There is a lot of controversy about adjuvant hormonal therapy for prostatic cancer including intermittent hormonal therapy, but the results are not gotten yet.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Castration; Chemotherapy, Adjuvant; Diethylstilbestrol; Drug Therapy, Combination; Estrogens; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Meta-Analysis as Topic; Prostatectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic

The role of androgen deprivation therapy in prostate carcinoma is controversial in earlier stages of disease. The authors examined the time trends and patterns of use for androgen deprivation in the form of gonadotropin-releasing hormone (GnRH) agonists or orchiectomy, in population-based tumor registries.. Data were obtained from the linked Surveillance, Epidemiology and End Results-Medicare database. A total of 100,274 men with prostate carcinoma diagnosed from 1991 through 1999 were selected. The main outcome was the proportion of men who received >/= 1 dose of a GnRH agonist in the first 6 months of diagnosis. This was plotted by year and stratified for age, grade, stage as well as primary versus adjuvant usage. Multiple logistic regression was used to examine predictors of GnRH agonist use in the subset of patients with localized cancer.. There was a consistent increase in GnRH agonist use by year for all ages, stages, and grades. Even in men >/= 80 years with localized stage and low to moderate grade tumors, primary GnRH agonist use increased over the study period, from 3.7% in 1991 to 30.9% in 1999 (P < 0.001). The multivariable analysis showed that significant variability in GnRH agonist use existed among SEER geographic regions.. The use of GnRH agonists for prostate carcinoma increased dramatically during the 1990s. This increase occurred across all stages and histologic grades of prostate carcinoma, and was greatest in patients >/= 80 years.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Databases as Topic; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Neoplasm Staging; Orchiectomy; Predictive Value of Tests; Prostatic Neoplasms; Registries; SEER Program; Time Factors; Treatment Outcome

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Nitriles; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Survival Rate; Tosyl Compounds

This article reviews the clinical disease-free survival (DFS) and disease-related mortality (DRM) data from published prospective, randomized trials of goserelin, given alone as adjuvant treatment or combined with a nonsteroidal antiandrogen as neoadjuvant treatment in patients with locally advanced or localized prostate cancer. Four trials were of radiotherapy and one of radical prostatectomy. The five trials included > 3500 patients and the median follow-up was 4.8-7.1 years. There were statistically significant improvements in clinical DFS with goserelin support relative to the control treatment in all five trials (each log-rank P

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Evaluation; Follow-Up Studies; Goserelin; Humans; Male; Prostatectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Treatment Outcome

In our institution, rotational 3D-conformal radiation therapy (also called conformation therapy) has been applied since the late 1970s to conform the target volume of high-dose radiation to the cancerous tissue while minimizing radiation to the surrounding normal tissues. This technique has been used most commonly to treat prostate cancers in combination with hormonal therapy. The results of Stage B2/C prostate cancer treated with this method were analyzed.. Between 1987 and 1997, 33 cases of prostate cancer were definitively treated with this method: 9 Stage B2 tumors and 24 Stage C tumors. Of these 33 tumors, 3 were well differentiated, 18 were moderately differentiated, and 12 were poorly differentiated. The average patient age was 75.6 years. The median pretreatment PSA value was 23.8 ng/ml. The total radiation dose ranged from 60 Gy to 70 Gy (average: 63.5 Gy) with conventional fractionation. Hormone therapy was administered permanently; the primary hormonal agent was diethylstilbestrol phosphate.. The overall survival rate after 5 years was 58.2% and that after 10 years was 29.6%. The biochemical relapse-free rate after 5 years was 87.0% and that after 10 years was still 87.0%. There were 4 cases of biochemical failure, but no cases of death from prostate cancer. Stage, differentiation, and pretreatment PSA value were not prognostic factors. One of the 2 cases with delayed complications was a case of RTOG Grade 3 gastrointestinal complication.. Rotational 3D-conformal radiation therapy combined with hormone therapy might be promising for the treatment of prostate cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Chlormadinone Acetate; Diethylstilbestrol; Disease-Free Survival; Flutamide; Follow-Up Studies; Gastrointestinal Diseases; Goserelin; Humans; Imaging, Three-Dimensional; Japan; Life Tables; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostatic Neoplasms; Radiation Injuries; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Retrospective Studies; Rotation; Survival Analysis; Treatment Outcome; Urination Disorders

Adjuvant hormone treatment with radiotherapy has been demonstrated in two studies (Bolla and RTOG 8531) to be beneficial in patients with locally advanced prostate cancer. However, the vast majority of patients with early prostate cancer can be cured with radiotherapy alone. Subset analysis combining RTOG 8610 and RTOG 8531 has demonstrated a survival benefit only for patients with a biopsy Gleason score < or =6 after short-term neoadjuvant hormonal therapy. The results of ongoing research will further clarify the use of hormone treatment with radiotherapy in patients with low and intermediate risk.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome

In the recent years, researches on drugs for prostate cancer have received more attention than ever before. This article reviews the mechanism and efficacy of such prostate cancer drugs as bicalutamide, medroxyprogesterone acetate, megestrol acetate, flutamide and so on, as well as the clinical data and clinical uses of calcitriol analogue EB1089, SR233377, etc.

Topics: Androgen Antagonists; Antineoplastic Agents; Goserelin; Humans; Male; Prostatic Neoplasms; Sulfonamides; Suramin; Thioxanthenes

In the 60 years since Huggins first demonstrated the hormone dependency of prostate cancer, the introduction of various means of hormonal manipulation has resulted in modest achievements. Orchiectomy reduced testosterone but was irreversible and associated with reduced quality of life. Diethylstilbestrol (DES) represented the first alternative to surgical castration. However, cardiovascular adverse events severely limited its use. The luteinizing hormone-releasing hormone (LHRH) agonists offered true medical castration but suffered from problems of testosterone surge and tumor flare. The introduction of antiandrogens in combination with LHRH agonists appears on meta-analysis not to have improved survival and has implications for the cost and convenience of therapy, as well as added toxicity. Gonadotropin-releasing hormone (GnRH) antagonists offer for the first time a truly rapid medical means of reducing testosterone and also suppress follicle-stimulating hormone (FSH). However, the clinical benefit of this new class of drugs remains to be evaluated.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Diethylstilbestrol; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Oligopeptides; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Patients with locally advanced prostate cancer (TNM clinical stage T3, T4) who were treated using external-beam radiotherapy (EBRT) and 3 years of androgen deprivation therapy (ADT) were compared with patients treated with EBRT alone and were shown to have a survival benefit. Studies that address the same question for patients with clinically localized disease (stage T1, T2) have been completed and are awaiting follow-up study. A rate of decrease in the serum hemoglobin level of > or =1 g/dL during the first month of neoadjuvant ADT predicted for a significantly worse disease-free survival outcome, as defined by the prostate-specific antigen, for patients with intermediate- and high-risk clinically localized disease who were undergoing EBRT and ADT. Validation of this predictive factor by others is needed.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Disease Progression; Disease-Free Survival; Goserelin; Hemoglobins; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Survival Rate

A 66-year-old, man was referred to our hospital for further examination of multiple pulmonary nodules on chest X-ray performed on medical examination. He was referred to our clinic because his chief complaint was poor urinary stream. Prostatic cancer was suspected on digital rectal examination and magnetic resonance imaging. Serum prostatic specific antigen (PSA) level was 134.9 ng/ml. Histological examination of transrectal prostatic sextant biopsy revealed well differentiated adenocarcinoma of prostate. Abdominal computed tomography-scan, gastro-intestinal tract examination and bone scintigraphy demonstrated no other primary lesions or distant metastases. Under the diagnosis of prostatic cancer with multiple pulmonary metastasis, we performed total androgen blockade (TAB) consisting of luteinizing hormone releasing hormone agonist and flutamide following dietylstilbestrol (DES) intravenous injection therapy. After three months, pulmonary nodules disappeared on chest X-ray and PSA level decreased to below 0.1 ng/ml. Pulmonary nodules also disappeared on CT-scan after six months after TAB. He is alive and free from the recurrence for 42 months.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Diethylstilbestrol; Drug Administration Schedule; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lung Neoplasms; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Tomography, X-Ray Computed

Goserelin acetate is a LH-RH agonist developed by AstraZeneca (formerly ICI, UK), and has been used clinically for the treatment of prostate cancer as a 4-week controlled-release formulation (Zoladex 3.6 mg depot). Recently, a new drug (Zoladex LA 10.8 mg depot) with 3-month controlled-release formulation was developed and became commercially available in Japan. In the randomized comparative phase III studies carried out with global bases, single administration of the new drug yielded almost equivalent anti-testosterone effect and the same serum level of the previous 3.6 mg depot formulation in 3-times continuous administration. In these studies, adverse drug reactions, which were mainly due to pharmacological effects of the new drug and minimal, were found in 52.6% (41/78) compared with 54.8% (46/84) with the previous 3.6 mg depot formulation. In the phase III studies, there were no significant differences in average serum testosterone levels between the two formulations at 12 and 13 weeks after administration. In the Japanese late phase II study with untreated patients, castration effect was observed in all 20 cases entered in the trial. In 20 cases in which treatment was switched from 3.6 mg depot to the new formulation, there were no significant changes in serum testosterone levels at castration level of the untreated patients, 90% (18/20) responded to the treatment, and normalization of PSA level was found in 75.0% (15/20). The adverse drug reactions were mainly increased triglyceride level and hot flushes. In the retrospective evaluation of untreated patients in this trial and the post-marketing clinical trial data for 3.6 mg depot, it was concluded that the new drug had almost the same efficacy and safety profile as 3.6 mg depot in Japanese people. These results indicate that Zoladex LA 10.8 mg depot has the same efficacy and safety as 3.6 mg depot with administration every three months, the burden of injection of LH-RH agonist can be reduced. This new medication can be considered a new standard for treatment of prostate cancer.

Topics: Animals; Antineoplastic Agents, Hormonal; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms; Retrospective Studies

The use of the luteinising hormone releasing hormone (LHRH) analogues--goserelin (Zoladex, AstraZeneca) and leuprorelin (Prostap, Wyeth)--is well established and forms the backbone of the treatment of locally advanced and metastatic prostate cancer. Comparable efficacy with orchidectomy and, historically, diethylstilbestrol (DES) is accepted, with the advantages of reversibility and limited thromboembolic and cardiovascular toxicity, respectively. Side effects such as hot flushes, loss of libido, lethargy and decreased bone mineral density have recently stimulated more interest in the use of non-steroidal anti-androgens such as bicalutamide (Casodex, AstraZeneca) in locally advanced disease. Although better tolerated, bicalutamide has significant problems with gynaecomastia and breast pain. Maximal androgen blockade using LHRH analogues and their adjuvant use with radiotherapy are discussed, as well as their experimental application in intermittent androgen suppression therapy. Similar side effect profiles are reported for the LHRH analogues but injection tolerability differs with the smaller 23G needle for Prostap 3 compared to the 16G needle for Zoladex LA. There is no evidence to suggest a difference in the efficacy between the LHRH analogues goserelin and leuprorelin, although no direct comparison has yet been undertaken.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Clinical Trials as Topic; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms

Topics: Antineoplastic Agents, Hormonal; Clinical Trials as Topic; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Quality of Life

Topics: Antineoplastic Agents, Hormonal; Drug Administration Schedule; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Luteinizing Hormone; Male; Prostatic Neoplasms; Substance Withdrawal Syndrome; Testosterone; Time Factors

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Castration; Chlormadinone Acetate; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Nitriles; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Tosyl Compounds

Topics: Adenoviridae; Androgen Antagonists; Antibodies, Monoclonal; Antineoplastic Agents; Aziridines; Cancer Vaccines; Drug Design; Flurbiprofen; Genetic Therapy; Genetic Vectors; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Oligonucleotides, Antisense; Panitumumab; Prostate-Specific Antigen; Prostatic Neoplasms

Prostatic cancer is rarely diagnosed by detection of lung metastases. We report a case of prostatic cancer in a 73-year-old man detected by abnormalities in chest X-ray and serum prostate specific antigen (PSA) level. He was initially admitted to our hospital due to elevation of PSA level. On the first transperineal prostatic needle biopsy, prostatic cancer was not detected and he was followed. Seven months after the first biopsy, chest X-ray revealed multiple abnormal nodules in the lung fields bilaterally and PSA level was again elevated. A second prostatic biopsy and whole-body examination were performed, and he was diagnosed with moderately differentiated prostatic adenocarcinoma with multiple lung metastases. Complete androgen blockade therapy was performed immediately. Two months after the beginning of treatment, PSA level was normalized and the multiple lung metastases had completely disappeared. There has been no evidence of recurrence or PSA relapse 24 months after detection of the prostatic cancer. This is the 26th case of prostatic cancer diagnosed in Japan following detection of multiple lung metastases.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Lung Neoplasms; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiography; Treatment Outcome

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Clinical Trials as Topic; Combined Modality Therapy; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Multicenter Studies as Topic; Prostatic Neoplasms; Survival Analysis; Treatment Outcome

Prostate cancer has become the most common cancer among American men and is second only to lung cancer as a cause of male cancer-related death. Several treatment options exist for different stages of prostate cancer including observation, prostatectomy, radiation therapy, chemotherapy, and hormone therapy. Hormone therapy has evolved from the use of estrogens to gonadotropin-releasing hormone (GnRH) agonists and recently, investigational GnRH antagonists. GnRH receptor agonists such as leuprolide, bruserelin and goserelin have been used for the treatment of prostate cancer. These agonists eventually cause the inhibition of lutenizing hormone production, which in turn causes a suppression of testosterone and dihydrotestosterone, on which continued growth of prostate cancer cells depend. Several comparative studies of leuprorelin administered as daily injections or monthly depot injections have been reported. Disease progression was prevented in more than 72% of men administered daily leuprorelin, and in 82% to 89% of those receiving monthly depots. Another synthetic GnRH analog, goserelin, has been studied in a similar population of men with daily injections producing partial responses in 60% to 80% of men with previously untreated prostate cancer. Abarelix, a peptide antagonist of GnRH receptor, is also being studied for the treatment of prostate cancer. The discovery and development of GnRH antagonists may provide an important advance for patients with prostate cancer. Clearly the studies described herein, as well as many others, outline an exciting era of research to define the optimal use of hormonal therapy in prostate cancer.

Topics: Antineoplastic Agents, Hormonal; Buserelin; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Testosterone

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Goserelin; Humans; Leuprolide; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms

Topics: Antineoplastic Agents, Hormonal; Autacoids; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms

Topics: Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Libido; Male; Prostatic Neoplasms; Substance Withdrawal Syndrome

Topics: Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms

With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic review of the evidence from randomized controlled trials on the relative effectiveness of alternative strategies for androgen suppression as treatment of advanced prostate cancer. Three key issues are addressed: (1) the relative effectiveness of the available methods for monotherapy (orchiectomy, luteinizing hormone-releasing hormone [LHRH] agonists, and antiandrogens), (2) the effectiveness of combined androgen blockade compared to monotherapy, and (3) the effectiveness of immediate androgen suppression compared to androgen suppression deferred until clinical progression. Outcomes of interest are overall, cancer-specific, and progression-free survival; time to treatment failure; adverse effects; and quality of life. Two supplementary analyses were conducted for each key question: (1) meta-analysis of overall survival at 2 years (questions 1 and 2) and 5 years (questions 2 and 3), and (2) cost-effectiveness analysis.. The MEDLINE, CANCERLIT, and EMBASE databases were searched from 1966 to March 1998, and Current Contents to August 24, 1998, for the terms: leuprolide (Lupron); goserelin (Zoladex); buserelin (Suprefact); flutamide (Eulexin); nilutamide (Anandron, Nilandron); bicalutamide (Casodex); cyproterone acetate (Androcur); diethylstilbestrol (DES); and orchiectomy (castration, orchidectomy). The search was then limited to human studies indexed under the MeSH term "prostatic neoplasms" and by the UK Cochrane Center search strategy for randomized controlled trials. Total yield was 1,477 references.. We Reports of efficacy outcomes were limited to randomized controlled trials. Phase II studies that reported on withdrawals from therapy and all studies reporting on quality of life were also included.. The systematic review used a prospectively designed protocol conducted by two independent reviewers, with disagreements resolved by consensus. The meta-analysis combined data on overall survival using a random effects model. The cost-effectiveness analysis used a decision analysis model of advanced prostate cancer with health states and transitions derived from the literature and estimates of effectiveness derived from the meta-analysis. The cost-effectiveness analysis is conducted from a societal perspective, consistent with the guidelines of the U.S. Public Health Service Panel on Cost-Effectiveness in Health and Medicine.. Survival after treatment with an LHRH agonist is equivalent to survival after orchiectomy. The available LHRH agonists are equally effective, and no LHRH agonist is superior to the other when adverse effects are considered. Survival may be somewhat lower with use of a nonsteroidal antiandrogen. There is no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade or monotherapy. Meta-analysis of the limited data available shows a statistically significant difference in survival at 5 years that favors combined androgen blockade. However, the magnitude of this difference is of questionable clinical significance. For the subgroup of patients with good prognosis, there is no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. No evidence is yet available from randomized controlled trials of androgen suppression initiated at prostate-specific antigen (PSA) rise after definitive therapy for clinically localized disease. For patients who are newly diagnosed with locally advanced or asymptomatic metastatic disease, the evidence is insufficient to determine whether primary androgen suppression initiated at diagnosis improves outcomes. (ABSTRACT TRUNCATED)

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Cost-Benefit Analysis; Evidence-Based Medicine; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Treatment Outcome

Endocrine therapy for prostate cancer has been changing rapidly. While LH-RH agonists have been popularly used in medication, their long-acting sustained release formulation is about to be introduced to clinics in Japan. LH-RH antagonists, which have not attracted much attention of clinicians because of adverse reactions, are also going to be put into practical use in the near future. Bicalutamide, which is considered to have greater usefulness than other anti-androgens, is now under regulatory review by the authorities for approval. In addition, a broader range of endocrine therapies is being studied for treatment of prostate cancer. In terms of treatment methods, a number of attempts are made in selection of subject patients, treatment timing, combination treatment and so on.

Topics: Adult; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Nitriles; Prostatic Neoplasms; Survival Rate; Testosterone; Tosyl Compounds

Ever since prostatic carcinoma was discovered to be dependent on the hormone androgen for its proliferation, androgen deprivation has been the treatment of choice for advanced cases of prostate cancer. Originally, treatment was limited to surgical castration or estrogen therapy. However, the introduction of luteinizing hormone-releasing hormone analogues, antiandrogens, and newer treatment modalities, such as combined androgen blockade, has made choosing a treatment strategy more complex. Assuming that each modality is equally effective, emphasis should be placed on increasing patient tolerance and compliance by the use of long-acting, nontoxic treatments with simple dosing regimens and minimal side effects. This review focuses on the factors influencing the final choice of treatment strategy.

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Flutamide; Goserelin; Humans; Imidazoles; Imidazolidines; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds

There can be seen many investigations to examine the effects and benefits of total androgen blockade (TAB), combining an antiandrogen with surgical castration or a LH-RH analogue, for advanced prostate cancer. This review summarizes the concept, theory, method and clinical application of TAB. The concept of TAB was supported by reports that show a survival advantage using the combined blockade over LH-RH analogue alone. The theory of TAB proposes that suppression of all androgen production, adrenal and testicular androgen, should result in a better response than standard hormonal management such as castration and/or estrogens. In Japan, Chlormadinone acetate (100 mg twice daily) or Flutamide (375 mg three times daily) is orally administered and Leuprorelin acetate (3.75 mg every 4 weeks) or Goserelin acetate (3.6 mg every 4 weeks) is administered by hypodermic injection. There have been unresolved controversies surrounding this therapeutic modality, therefore future studies should help to define the role of TAB.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Chlormadinone Acetate; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms

Management of patients with metastatic prostate cancer differs from that of patients with other metastatic solid tumors. Because the treating physician is usually the patient's urologist, the primary care physician's main role may be to relieve pain and treat the patient for common side effects of hormone therapies. By being familiar with the forms of systemic treatment-including orchiectomy and the use of estrogens, luteinizing hormone-releasing hormone agonists, and antiandrogens-the primary care physician can also assist patients in making treatment decisions that are individualized to the specifics of disease state, comorbid conditions, age, and value systems.

Topics: Antineoplastic Agents, Hormonal; Bone Neoplasms; Estrogens; Goserelin; Humans; Male; Orchiectomy; Pain Management; Palliative Care; Prostatic Neoplasms

Goserelin is a gonadotrophin-releasing hormone (GnRH) analogue which during long term administration reduces circulating levels of gonadotrophins (luteinising hormone and follicle stimulating hormone) and sex hormones. Goserelin is administered subcutaneously as a biodegradable depot formulation incorporating 3.6mg of the drug, which is released continuously over 4 weeks. In men with untreated advanced prostate cancer, monthly goserelin 3.6mg has been confirmed as similar in efficacy to surgical castration and diethylstilbestrol (stilboestrol) 3mg daily taken orally. Goserelin is better tolerated than diethylstilbestrol and appears to have a more favourable effect on quality of life than surgical castration. Treatment of prostate cancer with a combination of goserelin and an antiandrogen remains controversial as a result of inconsistent findings, despite extended data from a large trial which indicated an advantage for the combined regimen over surgical castration with respect to duration of time to progression and survival. Combination therapy also minimises the initial increase in signs and symptoms (disease flare) that occurs in up to 4% of patients at the beginning of treatment with a GnRH analogue. Surgical castration remains the treatment of choice in patients at risk of metastatic compression of the spinal cord or ureteric obstruction. However, goserelin is an effective alternative to surgery, or estrogen therapy, in men with previously untreated advanced prostate cancer. Goserelin seems to be preferred to surgery by the majority of patients given a choice of treatment, and importantly in a palliative care situation where there are no survival advantages for treatment alternatives, it appears to have a more beneficial effect on the quality of life than surgery.

Topics: Absorption; Aged; Antineoplastic Combined Chemotherapy Protocols; Estramustine; Estrogens; Flutamide; Gonadotropins; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Steroids

Topics: Adrenalectomy; Androgen Antagonists; Combined Modality Therapy; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Goserelin; History, 18th Century; Humans; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prognosis; Prostatic Neoplasms

Androgen ablation by bilateral orchiectomy or by the administration of gonadotropin-releasing hormone (GnRH) agonists has become standard treatment for advanced prostate cancer. However, serum levels of dihydrotestosterone (DHT) remain at about 40% of the precastration levels due to the conversion of the adrenal androgens. Maximal androgen blockade (MAB) aims to block the stimulatory action of this adrenal-derived DHT by adding antiandrogens to surgical or medical castration. Some of the largest and best controlled randomized trials in Europe and the United States have shown statistically better progression-free survival, overall survival, and survival from death by prostate cancer with MAB than with monotherapy with a GnRH agonist or with bilateral orchiectomy. Trial 30853 of the European Organization for Research and Treatment of Cancer (EORTC) compared MAB using a combination of goserelin subcutaneous depot (Zoladex; Zeneca Pharmaceuticals, Macclesfield, UK) and flutamide with bilateral orchiectomy. Some other published trials did not find the differences revealed by EORTC 30853, however, and so an overview or meta-analysis of trials on the effects of MAB was organized jointly by the American Cancer Society, the Urological Group of the EORTC, and the International Prostate Health Council. Preliminary results on some of the 23 trials included in the meta-analysis showed an advantage of the GnRH agonist therapy in combination with an anti-androgen, particularly in time to progression. If time to progression is viewed as improved quality of life due to the absence of symptoms, a net result in favor of the combination therapy is noted. The MAB trials, using flutamide as the antiandrogen, also showed a small but distinct improvement in survival with the combination treatment. An emphasis on prognostic factors allows treatment decisions to be reached more easily.

Topics: Combined Modality Therapy; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Male; Orchiectomy; Prognosis; Prostatic Neoplasms; Survival Analysis; Treatment Outcome

Radical prostatectomy is an excellent form of treatment of pathologically organ-confined prostatic carcinoma. However, most clinically localized prostatic cancers have pathologic evidence of extracapsular spread, limiting the effectiveness of radical surgery in curing this disease. To improve the organ-confined rate of prostate cancer, we studied the effect of preoperative or neoadjuvant androgen deprivation therapy (ADT). Our initial attempts focused on downstaging locally advanced tumors (T3) with neoadjuvant diethylstilbestrol (3 mg/d). Our study of 59 patients revealed that although there were significant clinical signs of downstaging, most patients still had extraprostatic disease. However, a subset of patients demonstrated marked pathologic regression, so we initiated a nonrandomized but controlled study of neoadjuvant ADT (goserelin acetate and flutamide for 3 months) followed by radical prostatectomy in patients with clinically localized prostate cancer. Of 72 control and 69 study patients, the rate of organ-confined disease was 48% and 74% (including 4% with no detectable residual carcinoma), respectively. In addition, the margin-positive rate was 33% and 10%, respectively. As demonstrated in the previous study, changes in serum prostate-specific antigen, transrectal ultrasonographic evaluations, and digital rectal examinations could not predict those patients with favourable pathology. Our results suggest that neoadjuvant ADT may improve the pathologic stage in some prostatic carcinomas and is worthy of further investigation in the efforts to augment the effectiveness of radical prostatectomy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Flutamide; Goserelin; Humans; Male; Preoperative Care; Prostatectomy; Prostatic Neoplasms

Androgen ablation by bilateral orchidectomy has long been considered the gold standard against which other forms of treatment for the management of advanced prostate cancer can be evaluated. It now is recognized that the use of luteinizing hormone-releasing hormone analogs provides a form of primary endocrine therapy that is as effective as surgical castration for the treatment of disseminated disease.

Topics: Androgen Antagonists; Clinical Trials as Topic; Diethylstilbestrol; Goserelin; Humans; Luteinizing Hormone; Male; Orchiectomy; Prostatic Neoplasms; Testosterone

Cancer of the prostate gland is the most frequently occurring malignant lesion in men. Because most prostate cells depend on androgen for growth, removal of testosterone by either orchiectomy or medical castration using diethylstilbestrol or a luteinizing hormone-releasing hormone (LHRH) analogue is first-line treatment for patients with symptomatic Stage D2 disease. The trend in hormonal therapy has been toward long-acting minimal-dosing high-compliance regimens, capitalizing on the recent availability of the long-acting LHRH analogues, which require only monthly injections to maintain castration levels of testosterone, and the nonsteroidal antiandrogen ICI 176,334, which (in early clinical trials) appears to block intracellular testosterone activity with a once-a-day oral regimen. To eliminate the rapid LH increase that can occur during early agonist therapy, combinations of LHRH analogues and antiandrogens (total androgen blockade) have been tested and appear promising. The effects of hormonal treatment in patients with symptomatic Stage D2 prostate cancer have been studied extensively and are relatively well understood. By contrast, hormonal treatment has not been explored in contemporary randomized Phase III trials of asymptomatic Stage D2, D1, or C disease, localized Stage B or A disease, or before prostate surgery or radiation treatment. Research must continue to determine the optimal regimen that suppresses testosterone activity with the least amount of toxicity.

Topics: Androgen Antagonists; Anilides; Animals; Antineoplastic Agents; Buserelin; Clinical Trials as Topic; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Nitriles; Orchiectomy; Prostatic Neoplasms; Tosyl Compounds

Goserelin is a synthetic analogue of gonadotrophin-releasing hormone (GnRH) [luteinising hormone-releasing hormone (LHRH); or gonadorelin] which stimulates gonadotrophin and sex hormone release in the short term, and then causes suppression with continued administration. Goserelin is given as a subcutaneous biodegradable depot incorporating 3.6 mg of the drug, which is released continuously at an average rate of 120 micrograms/day over 4 weeks. Monthly goserelin depot therapy produces partial disease remission or stabilisation in about 75% of men with previously untreated prostatic cancer, a rate equivalent to that achieved with orchidectomy or diethylstilbestrol (stilboestrol). The response to goserelin is more rapid than to diethylstilbestrol, and goserelin is better tolerated. About 30 to 45% of premenopausal women with breast cancer responded to goserelin using objective assessment criteria, suggesting comparability to ovariectomy. In benign hormone-dependent conditions, preoperative goserelin aids surgical removal of uterine leiomyoma (fibroids) and reduces blood loss, and 6 months of therapy relieves the signs and symptoms of endometriosis. The elevation in testosterone at the beginning of goserelin therapy can result in disease 'flare' in men with prostate cancer, and sex steroid suppression with continued treatment results in hot flushes and loss of libido in most patients. Thus, goserelin is an effective alternative to surgery or estrogen therapy in prostatic cancer palliation, and possibly to ovariectomy in premenopausal breast cancer. Other gynaecological conditions reliant on the pituitary-gonadal axis also appear amenable to hormone manipulation with goserelin.

Topics: Animals; Breast Neoplasms; Buserelin; Drug Evaluation; Endometriosis; Female; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Gonadotropins; Goserelin; Humans; Leiomyoma; Male; Menstruation Disturbances; Polycystic Ovary Syndrome; Prostatic Neoplasms; Uterine Neoplasms

Topics: Androgen Antagonists; Antineoplastic Agents; Buserelin; Delayed-Action Preparations; Estradiol Congeners; Goserelin; Humans; Leuprolide; Male; Orchiectomy; Prostatic Neoplasms

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Biodegradation, Environmental; Estrogens; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms

The identification of the decapeptide luteinizing hormone-releasing hormone (LHRH) has led to the development of LHRH agonists, which are a new class of drugs for the treatment of advanced prostate cancer. These peptides have a modified amino acid structure that makes them more potent than LHRH. Prolonged administration of LHRH agonists results in down-regulation of the LHRH receptors in the pituitary and decreased secretion of luteinizing hormone. The result is decreased production of testosterone by Leydig cells, which is the basis for the use of LHRH agonists to treat prostate cancer. The effectiveness of LHRH agonists has been demonstrated in the United States in several randomized, controlled clinical trials. Daily administration of leuprolide produced equivalent results compared with diethylstilbestrol (DES). More recently, in two separate, randomized studies, the long-acting LHRH agonist Zoladex (ICI Pharma, Wilmington, Delaware) produced the same objective response rate as DES or bilateral orchiectomy. The equivalent response rates obtained with LHRH agonists indicate that these drugs can now be considered a reasonable treatment option for patients with metastatic prostatic cancer.

Topics: Antineoplastic Agents; Buserelin; Clinical Trials as Topic; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms

Topics: Androgen Antagonists; Buserelin; Clinical Trials as Topic; Diethylstilbestrol; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms

The introduction of potent analogues of gonadotropin hormone-releasing hormone (GnRH) into clinical practice and their use in patients with metastatic prostatic carcinoma provides an effective alternative to the exogenous administration of pharmacologic doses of estrogens or surgical castration. Their advantages over estrogens are primarily related to a lower incidence of cardiovascular toxicity and gynecomastia. Their choice over orchiectomy is based on cosmetic and psychologic factors since their endocrine effects and clinical benefits are virtually the same. In this review, we describe the current experience with GnRH analogues in the treatment of prostatic carcinoma and discuss their use in the context of other endocrine manipulations. GnRH analogues act on the pituitary and indirectly affect gonadal function, and represent an opportunity for combination with other compounds capable of suppressing or interfering with the effects of circulating and androgens. The availability of several new compounds affecting different aspects of androgen metabolism provides promise for rational drug selection and testing.

Topics: Buserelin; Clinical Trials as Topic; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Goserelin; Humans; Leuprolide; Male; Nafarelin; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Testosterone

Topics: Buserelin; Castration; Chorionic Gonadotropin; Cosyntropin; Dexamethasone; Diethylstilbestrol; Estrogens; Goserelin; Hormones; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.. We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.. On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).. LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.. ClinicalTrials.gov, NCT04563936.

Topics: Antineoplastic Agents, Hormonal; East Asian People; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Pharmacobiological behavior differs between gonadotropin-releasing hormone (GnRH) antagonists and GnRH agonists. However, reliable evidence clarifying the difference between them is limited.. We aimed to elucidate the difference in recovery profile between GnRH antagonist (degarelix) and GnRH agonist (leuprorelin acetate or goserelin acetate) as short-term (12 weeks) neoadjuvant androgen deprivation therapy (ADT) prior to 125I-transperineal prostate brachytherapy (TPPB) for localized prostate cancer.. This study was initially designed as a single-center, prospective, open-label, randomized controlled trial. The primary endpoint was a serum testosterone level above the castration range (>50 ng/dl) after the cessation of 12-week neoadjuvant ADT (GnRH antagonist or GnRH agonists). All patients underwent 12 weeks of neoadjuvant ADT. The recovery profiles of hormones, prostate-specific antigen, total prostate volume (TPV), bone mineral density, and quality of life scores were investigated.. Testosterone recovery duration after the last injection was significantly longer in the GnRH antagonist arm than in the GnRH agonist arm (median, 27.3 vs. 4.8 weeks, p < 0.001). The serum levels of luteinizing hormone and follicle-stimulating hormone in the GnRH antagonist arm also remained significantly lower than those in the GnRH agonist arm between 16 and 24 weeks (p < 0.01). Meanwhile, reduction in TPV at the time of TPPB was comparable between both arms (p = 0.128). There were also no significant between-arm differences in the International Prostate Symptom Score and the International Index of Erectile Function scores.. The recovery patterns of hormonal profiles after short-term (12 weeks) neoadjuvant ADT differ between GnRH antagonists and GnRH agonists. The choice between these drugs matters and may have a clinical impact depending on the primary objective of ADT.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Brachytherapy; Gonadotropin-Releasing Hormone; Goserelin; Humans; Iodine Radioisotopes; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oligopeptides; Orchiectomy; Organ Size; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Testosterone; Time Factors; Treatment Outcome; Withholding Treatment

The optimal duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains controversial. The DART 01/05 trial was designed to determine whether long-term androgen deprivation is superior to short-term androgen deprivation when combined with high-dose radiotherapy. The 5-year results showed that 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy significantly improved biochemical control, metastasis, and overall survival, especially in patients with high-risk disease. In this report, we present the 10-year final results of the trial.. This open-label, phase 3, randomised, controlled trial was done in ten hospitals in Spain. The eligibility criteria included patients aged 18 years or older with histologically confirmed T1c to T3, N0, and M0 adenocarcinoma of the prostate, according to the 2002 classification of the American Joint Committee on Cancer, with intermediate-risk and high-risk factors, prostate-specific antigen (PSA) less than 100 ng/mL, and a Karnofsky performance score of at least 70%. Patients were randomly assigned (1:1) to receive 4 months of neoadjuvant and concomitant short-term androgen deprivation (STAD) plus high-dose radiotherapy (minimum dose 76 Gy; median dose 78 Gy) or to receive the same treatment followed by 24 months of adjuvant long-term androgen deprivation (LTAD), via a randomisation scheduled generated by Statistical Analysis Software programme (version 9.1) and an interactive web response system. Patients assigned to the STAD group received 4 months of neoadjuvant and concomitant androgen deprivation (oral flutamide 750 mg per day or oral bicalutamide 50 mg per day) with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy was added during the first 2 months of treatment. Patients assigned to LTAD continued with goserelin every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival at 5 years. For this 10-year study we analysed overall survival, metastasis-free survival, biochemical disease-free survival, and cause-specific survival. Analysis was by intention to treat. This trial is closed and is registered at ClinicalTrials.gov (NCT02175212) and in the EU Clinical Trials Register (EudraCT 2005-000417-36).. Between Nov 7, 2005, and Dec 20, 2010, 355 patients were enrolled. One patient in the STAD group withdrew from the trial, hence 354 participants were randomly assigned to STAD (n=177) or LTAD (n=177). The median follow-up was 119·4 months (IQR 100·6-124·3). The 10-year biochemical disease-free survival for LTAD was 70·2% (95% CI 63·1-77·3) and for STAD was 62·3% (54·9-69·7; hazard ratio [HR] 0·84; 95% CI 0·50-1·43; p=0·52). At 10 years, overall survival was 78·4% (72·1-84·8) for LTAD and 73·3% (66·6-80·0) for STAD (HR 0·84; 95% CI 0·55-1·27; p=0·40), and metastasis-free survival was 76·0% (69·4-82·7) for LTAD and 70·9% (64·0-77·8) for STAD (HR 0·90; 95% CI, 0·37-2·19; p=0·81). For the subgroup of high-risk patients, the 10-year biochemical disease-free survival was 67·2% (57·2-77·2) for LTAD and 53·7% (43·3-64·1) for STAD (HR 0·90; 95% CI 0·49-1·64; p=0·73), the 10-year overall survival was 78·5% (69·6-87·3) for LTAD and 67·0% (57·3-76·7) for STAD (HR 0·58; 95% CI 0·33-1·01; p=0·054), and the 10-year metastasis-free survival was 76·6% (95% CI 67·6-85·6) for LTAD and 65·0% (55·1-74·8) for STAD (HR 0·89; 95% CI 0·33-2·43; p=0·82). Only 11 (3%) of 354 patients died from prostate cancer, all of them in the high-risk subgroup (five in the LTAD group and six in the STAD group). 76 (21%) patients died from other causes (mainly second malignancies in 31 [9%] and cardiovascular disease in 21 [6%]). No treatment-related deaths were observed.. After an extended 10-year follow-up, we were unable to support the significant benefit of LTAD reported at 5 years. However, the magnitude of the benefit was clinically relevant in high-risk patients. Intermediate-risk patients treated with high-dose radiotherapy do not benefit from LTAD. A biological characterisation with the inclusion of genomic testing is needed in the decision-making process.. Grupo de Investigación en Oncología Radioterápica and Sociedad Española de Oncología Radioterápica, the National Health Investigation Fund, and AstraZeneca.

Topics: Androgen Antagonists; Androgens; Goserelin; Humans; Male; Neoplasm Staging; Prostatic Neoplasms

Immunosuppressive cytokines have the potential to promote prostate cancer progression. Assessing their longitudinal changes may implicate mechanisms of progression, treatment resistance, and suggest new therapeutic targets.. Thirty-seven men with biochemically recurrent (BCR) prostate cancer who received 6 months of androgen deprivation therapy (ADT) and were monitored until the time to prostate-specific antigen progression (TTPP) were identified from a completed phase III trial (NCT00020085). Serum samples were archived at baseline, 3 months after ADT, and at TTPP. Cytokine concentrations were quantified using a 36-parameter electrochemiluminescence assay. The Wilcoxon signed-rank sum test was used to compare observations between time points. Kaplan-Meier analysis was used to calculate TTPP dichotomized by cytokine values above or below the median. Pearson's rank correlation coefficient was used to compare continuous variables.. Median TTPP was 399 days (range, 114-1641). Median prostate-specific antigen (PSA) at baseline and progression were 8.5 and 5.3 ng/mL, respectively. Twenty-three patients (62%) achieved undetectable PSA with ADT. Castrate levels of testosterone (<50 ng/dL) after 3 months of ADT occurred in 35 patients (95%). TNF-α (P = .002), IL-23 (P = .002), and CXCL10 (P = .001) significantly increased from baseline to post ADT. Certain cytokines correlated longitudinally: TNF-α correlated with IL-23 (r = .72; P < .001) and IL-8 (r = .59; P < .001) from baseline to post ADT and to PSA progression. Neutrophil-to-lymphocyte ratio correlated with IL-27 (r = .57; P < .001) and MIP-3α (r = .56; P < .001). Patients with a detectable PSA after ADT had elevated levels of IL-6 (P = .049) and IL-8 (P = .013) at PSA progression as compared with those with an undetectable PSA. There was a trend toward shorter TTPP in patients with TNF-α levels above the median (P = .042).. Several innate cytokines were associated with biochemically recurrent prostate cancer.

Topics: Aged; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Cohort Studies; Cytokines; Disease Progression; Double-Blind Method; Goserelin; Humans; Immune Tolerance; Immunity, Innate; Immunosuppressive Agents; Kallikreins; Leuprolide; Longitudinal Studies; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Thalidomide

Purpose Patients with high-risk prostate cancer after radical prostatectomy are at risk for death. Adjuvant androgen-deprivation therapy (ADT) may reduce this risk. We hypothesized that the addition of mitoxantrone and prednisone (MP) to adjuvant ADT could reduce mortality compared with adjuvant ADT alone. Methods Eligible patients had cT1-3N0 prostate cancer with one or more high-risk factors after radical prostatectomy (Gleason score [GS] ≥ 8; pT3b, pT4, or pN+ disease; GS 7 and positive margins; or preoperative prostate-specific antigen [PSA] > 15 ng/mL, biopsy GS score > 7, or PSA > 10 ng/mL plus biopsy GS > 6. Patients with PSA ≤ 0.2 ng/mL after radical prostatectomy were stratified by pT/N stage, GS, and adjuvant radiation plan and randomly assigned to ADT (bicalutamide and goserelin for 2 years) or ADT plus six cycles of MP. The primary end point was overall survival (OS). Median OS was projected to be 10 years in the ADT arm, requiring 680 patients per arm to detect a hazard ratio of 1.30 with 92% power and one-sided α = .05. Results Nine hundred sixty-one eligible intent-to-treat patients were randomly assigned to ADT or ADT + MP from October 1999 to January 2007, when the Data Safety Monitoring Committee recommended stopping accrual as a result of higher leukemia incidence with ADT + MP. Median follow-up was 11.2 years. The 10-year OS estimates were 87% with ADT (expected 50%) and 86% with ADT + MP (hazard ratio, 1.06; 95% CI, 0.79 to 1.43). The 10-year estimate for disease-free survival was 72% for both arms. Prostate cancer was the cause of death in 18% of patients in the ADT arm and 22% in the ADT + MP arm. More patients in the MP arm died of other cancers (36% v 18% in ADT alone arm). Conclusion MP did not improve OS and increased deaths from other malignancies. The DFS and 10-year OS in these patients treated with 2 years of ADT were encouraging compared with historical estimates, although a definitive conclusion regarding value of ADT may not be made without a nontreatment control arm.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents; Biopsy; Combined Modality Therapy; Glucocorticoids; Goserelin; Humans; Male; Middle Aged; Mitoxantrone; Neoplasm Grading; Neoplasm Staging; Nitriles; Prednisone; Prostatectomy; Prostatic Neoplasms; Survival Rate; Tosyl Compounds; Treatment Outcome

Non-inferiority in the cumulative castration rate of the 3-month formulation of degarelix compared with the 3-month formulation of goserelin was evaluated in subjects with prostate cancer. A phase III, open-label, parallel-arm study was carried out. An initial dose of 240 mg degarelix or 3.6 mg goserelin was given s.c.; after day 28, a maintenance dose of 480 mg degarelix or 10.8 mg goserelin was given once every 84 days. Non-inferiority in castration rate and safety of degarelix to goserelin were evaluated. The primary end-point was the cumulative castration rate from day 28 to day 364 and the non-inferiority margin was set to be 10%. A total of 234 subjects with prostate cancer were randomized to the degarelix group (n = 117) and the goserelin group (n = 117). The cumulative castration rate was 95.1% in the degarelix group and 100.0% in the goserelin group. As there were no events in the goserelin group, an additional analysis was carried out using 95% confidence intervals of the difference in the proportion of subjects with castration. Analyses indicated the non-inferiority of the 3-month formulation of degarelix to goserelin. Degarelix showed more rapid decreases in testosterone, luteinizing hormone, follicle stimulating hormone, and prostate-specific antigen levels compared with goserelin. The most common adverse events in the degarelix group were injection site reactions. Non-inferiority of the 3-month formulation of degarelix to goserelin was shown for testosterone suppression. The 3-month formulation of degarelix was also found to be tolerated as an androgen deprivation therapy for patients with prostate cancer. This trial was registered with ClinicalTrials.gov (identifier NCT01964170).

Topics: Aged; Antineoplastic Agents, Hormonal; Asian People; Constipation; Dose-Response Relationship, Drug; Drug Administration Schedule; Goserelin; Humans; Japan; Male; Nasopharyngitis; Oligopeptides; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Outcome

The NRG/RTOG 9413 study showed that whole pelvic radiotherapy (WPRT) plus neoadjuvant hormonal therapy (NHT) improved progression-free survival in patients with intermediate-risk or high-risk localised prostate cancer compared with prostate only radiotherapy (PORT) plus NHT, WPRT plus adjuvant hormonal therapy (AHT), and PORT plus AHT. We provide a long-term update after 10 years of follow-up of the primary endpoint (progression-free survival) and report on the late toxicities of treatment.. The trial was designed as a 2 × 2 factorial study with hormonal sequencing as one stratification factor and radiation field as the other factor and tested whether NHT improved progression-free survival versus AHT, and NHT plus WPRT versus NHT plus PORT. Eligible patients had histologically confirmed, clinically localised adenocarcinoma of the prostate, an estimated risk of lymph node involvement of more than 15% and a Karnofsky performance status of more than 70, with no age limitations. Patients were randomly assigned (1:1:1:1) by permuted block randomisation to receive either NHT 2 months before and during WPRT followed by a prostate boost to 70 Gy (NHT plus WPRT group), NHT 2 months before and during PORT to 70 Gy (NHT plus PORT group), WPRT followed by 4 months of AHT (WPRT plus AHT group), or PORT followed by 4 months of AHT (PORT plus AHT group). Hormonal therapy was combined androgen suppression, consisting of goserelin acetate 3·6 mg once a month subcutaneously or leuprolide acetate 7·5 mg once a month intramuscularly, and flutamide 250 mg twice a day orally for 4 months. Randomisation was stratified by T stage, Gleason Score, and prostate-specific antigen concentration. NHT was given 2 months before radiotherapy and was continued until radiotherapy completion; AHT was given at the completion of radiotherapy for 4 months. The primary endpoint progression-free survival was analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00769548. The trial has been terminated to additional follow-up collection and this is the final analysis for this trial.. Between April 1, 1995, and June 1, 1999, 1322 patients were enrolled from 53 centres and randomly assigned to the four treatment groups. With a median follow-up of 8·8 years (IQR 5·07-13·84) for all patients and 14·8 years (7·18-17·4) for living patients (n=346), progression-free survival across all timepoints continued to differ significantly across the four treatment groups (p=0·002). The 10-year estimates of progression-free survival were 28·4% (95% CI 23·3-33·6) in the NHT plus WPRT group, 23·5% (18·7-28·3) in the NHT plus PORT group, 19·4% (14·9-24·0) in the WPRT plus AHT group, and 30·2% (25·0-35·4) in the PORT plus AHT group. Bladder toxicity was the most common grade 3 or worse late toxicity, affecting 18 (6%) of 316 patients in the NHT plus WPRT group, 17 (5%) of 313 in the NHT plus PORT group, 22 (7%) of 317 in the WPRT plus AHT group, and 14 (4%) of 315 in the PORT plus AHT group. Late grade 3 or worse gastrointestinal adverse events occurred in 22 (7%) of 316 patients in the NHT plus WPRT group, five (2%) of 313 in the NHT plus PORT group, ten (3%) of 317 in the WPRT plus AHT group, and seven (2%) of 315 in the PORT plus AHT group.. In this cohort of patients with intermediate-risk and high-risk localised prostate cancer, NHT plus WPRT improved progression-free survival compared with NHT plus PORT and WPRT plus AHT at long-term follow-up albeit increased risk of grade 3 or worse intestinal toxicity. Interactions between radiotherapy and hormonal therapy suggests that WPRT should be avoided without NHT.. National Cancer Institute.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Canada; Chemoradiotherapy; Dose Fractionation, Radiation; Drug Administration Schedule; Flutamide; Goserelin; Humans; Kallikreins; Leuprolide; Male; Neoplasm Grading; Neoplasm Staging; Progression-Free Survival; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors; United States

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug-Related Side Effects and Adverse Reactions; Goserelin; Humans; Longitudinal Studies; Male; Middle Aged; Patient Reported Outcome Measures; Progression-Free Survival; Prospective Studies; Prostatic Neoplasms; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors

In patients with prostate cancer (PCa), prostate enlargement may give rise to lower urinary tract symptoms (LUTS); many patients suffer from moderate-to-severe symptoms. We compare the efficacy of degarelix and goserelin plus bicalutamide in improving LUTS in PCa patients.. Data were pooled from three Phase 3, randomized clinical trials of once-monthly treatment for 12 weeks with degarelix (240/80 mg; n = 289) or goserelin (3.6 mg) plus bicalutamide (50 mg; n = 174) for initial flare protection. LUTS at weeks 4, 8, and 12 were compared to baseline. Clinically relevant LUTS relief was a ≥3-point International Prostate Symptom Score (IPSS) decrease. Adverse events were assessed throughout the trials.. Patients receiving degarelix had significantly greater decreases in IPSS vs. goserelin at week 12 (adjusted difference: -1.24; 95% CI -2.33 to -0.14, P = 0.03). Clinically relevant LUTS relief with degarelix was especially pronounced in patients with moderate-to-severe LUTS (baseline IPSS ≥13) (odds ratio; OR 2.31; 95% CI 1.19-4.47, P = 0.01) and advanced PCa (OR 2.36; 95% CI 1.10-5.04, P = 0.03). A twofold higher OR for early (week 4) LUTS relief was seen with degarelix vs. goserelin (OR 2.03; 95% CI 1.14-3.60, P = 0.02). No difference in total prostate volume or urinary tract infection-related adverse events (2%) was seen between treatment groups.. An early, significant and clinically more pronounced improvement of LUTS, especially in patients with moderate-to-severe LUTS or advanced PCa, was seen with degarelix vs. goserelin plus bicalutamide.

Topics: Aged; Analysis of Variance; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Goserelin; Humans; Lower Urinary Tract Symptoms; Male; Nitriles; Oligopeptides; Organ Size; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Tosyl Compounds; Treatment Outcome

To assess the effectiveness and safety of tamsulosin combined with androgen deprivation therapy (ADT) for lower urinary tract symptoms (LUTS) in advanced prostate cancer (PC) patients.. Ninety PC patients with moderate-to-severe LUTS randomized into two groups of 45 each. One group received ADT (group 1), and the other received ADT plus tamsulosin (group 2) for 24 weeks. The outcome measures were changes in the International Prostate Symptom Score (IPSS), IPSS obstructive and irritative subscores, quality of life (QoL), maximum urinary flow rate (Q. Both ADT monotherapy and ADT plus tamsulosin significantly improved IPSS,QoL score, Q. Additional administration of tamsulosin showed significantly greater and sooner relief in LUTS than ADT monotherapy, with good acceptability. It is feasible that ADT is used alone after 16-24 weeks of combination therapy.

Topics: Adrenergic alpha-1 Receptor Antagonists; Aged; Antineoplastic Combined Chemotherapy Protocols; Flutamide; Goserelin; Humans; Lower Urinary Tract Symptoms; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Severity of Illness Index; Sulfonamides; Tamsulosin; Time Factors; Urodynamics

Trial RTOG 9202 was a phase 3 randomized trial designed to determine the optimal duration of androgen deprivation therapy (ADT) when combined with definitive radiation therapy (RT) in the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate. Long-term follow-up results of this study now available are relevant to the management of this disease.. Men (N=1554) with adenocarcinoma of the prostate (cT2c-T4, N0-Nx) with a prostate-specific antigen (PSA) <150 ng/mL and no evidence of distant metastasis were randomized (June 1992 to April 1995) to short-term ADT (STAD: 4 months of flutamide 250 mg 3 times per day and goserelin 3.6 mg per month) and definitive RT versus long-term ADT (LTAD: STAD with definitive RT plus an additional 24 months of monthly goserelin).. Among 1520 protocol-eligible and evaluable patients, the median follow-up time for this analysis was 19.6 years. In analysis adjusted for prognostic covariates, LTAD improved disease-free survival (29% relative reduction in failure rate, P<.0001), local progression (46% relative reduction, P=.02), distant metastases (36% relative reduction, P<.0001), disease-specific survival (30% relative reduction, P=.003), and overall survival (12% relative reduction, P=.03). Other-cause mortality (non-prostate cancer) did not differ (5% relative reduction, P=.48).. LTAD and RT is superior to STAD and RT for the treatment of locally advanced nonmetastatic adenocarcinoma of the prostate and should be considered the standard of care.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Combined Modality Therapy; Disease-Free Survival; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors; Treatment Outcome

The optimal treatment for high-risk prostate cancer (PCa) remains to be established. We previously reported favorable, biochemical recurrence-free survival in high-risk PCa patients treated with a neoadjuvant gonadotropin-releasing hormone agonist or antagonist and estramustine phosphate (EMP) (chemohormonal therapy; CHT) followed by radical prostatectomy (RP). We conducted a retrospective study to elucidate the clinical benefit of neoadjuvant CHT for high-risk PCa patients.. We reviewed the clinical and pathological records of 1254 PCa patients who underwent RP and bilateral pelvic lymphadenectomy between July 1996 and April 2016 at Hirosaki University. According to the D'Amico risk classification, we focused on 613 patients in the high-risk group. The high-risk PCa patients were further divided into two groups based on whether the patients received neoadjuvant CHT before RP (EMP group) or not (non-EMP group). The endpoint was overall survival (OS) after surgery.. The 5- and 10-year OS rates were 98.5 and 92.6%, respectively. The 10-year OS rate in the EMP group was significantly higher compared to the non-EMP group (P = 0.021). In multivariate analysis, administration of neoadjuvant CHT, lymph node involvement, and castration-resistant PCa status were significantly associated with OS.. RP with neoadjuvant CHT using EMP for high-risk PCa patients provided excellent long-term OS.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Estramustine; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Lymph Node Excision; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Survival Rate

The study aimed to evaluate the effects of metformin on insulin, C-peptide and body weight in Chinese men undergoing androgen deprivation therapy (ADT).. Between March 2013 and June 2014, 62 newly diagnosed patients of prostate cancer (PCa) due to receive ADT were recruited from 7 hospitals in Shanghai. Patients were randomized to respectively receive ADT (n = 31) and ADT + metformin (n = 31) for 6 months. Fasting and postprandial serum levels of insulin and C-peptide, blood glucose, prostate specific antigen, body mass index (BMI) and waist circumference (WC) were measured at the beginning and end of 6-month treatment.. Baseline characteristics were comparable between the 2 groups. Controlling for baseline levels, the ADT group had significantly higher levels of fasting glucose (p = 0.01) and higher WC (p = 0.04) than the ADT + metformin group. The levels of insulin, C-peptide and BMI did not differ significantly.. Metformin may be potentially efficient as a concomitant therapy on patients with PCa undergoing androgen deprivation treatment.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Humans; Hypoglycemic Agents; Male; Metformin; Nitriles; Orchiectomy; Pilot Projects; Prostatic Neoplasms; Tosyl Compounds

Androgen deprivation therapy (ADT) is associated with coronary heart disease and diabetes in men with prostate cancer (PCa); however, controversy exists regarding ADT and cardiovascular mortality (CVM) with limited data for lower risk disease.. We conducted a hypothesis-generating retrospective analysis to evaluate the relationship between short-course ADT and CVM in patients with clinically localized PCa enrolled in a phase III trial.. A total of 1979 men with clinically localized (T1b-2b, prostate-specific antigen [PSA] <20 ng/ml) PCa enrolled in Radiation Therapy Oncology Group (RTOG) 94-08 from 1994 to 2001. Patients were randomized to radiation therapy (RT) with or without short-course ADT (4 mo of gonadotropin-releasing hormone (GnRH) agonist therapy and antiandrogen). Median follow-up was 9.1 yr for survivors.. The Cox proportional hazards model assessed overall survival. The Fine-Gray proportional hazards model assessed disease-specific survival (DSS) and CVM. Covariates included age, race, weight, baseline cardiovascular disease, baseline diabetes, baseline hypertension, Gleason score, T stage, and PSA.. Short-course ADT improved overall survival and DSS and was not associated with an increased risk of CVM. Overall, 191 cardiovascular-related deaths were observed. At 10 yr, 83 patients (cumulative incidence rate: 10%) receiving RT and ADT versus 95 patients (cumulative incidence rate: 11%) receiving RT alone experienced CVM. The treatment arm was not associated with increased CVM (unadjusted hazard ratio: 1.07; confidence interval, 0.81-1.42; p=0.62). Increased CVM was not observed in patients at low risk of PCa death or at high risk of cardiac-related death.. Data from patients enrolled in RTOG 94-08 support the hypothesis that ADT does not increase CVM risk in men with clinically localized PCa treated with short-course GnRH agonist therapy. These data support ADT use in settings with proven survival benefit.. We investigated the controversial relationship between hormone therapy and cardiovascular mortality in men with prostate cancer (PCa) treated with radiation in a large randomized trial. Our data suggest that hormone therapy does not increase the risk of cardiovascular death in patients with clinically localized PCa and support the use of such therapy in settings with proven survival benefit.

Topics: Aged; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Flutamide; Follow-Up Studies; Goserelin; Humans; Incidence; Leuprolide; Male; Middle Aged; Proportional Hazards Models; Prostatic Neoplasms; Retrospective Studies; Survival Rate; Time Factors

The role of pelvic elective nodal irradiation (ENI) in the management of prostate cancer is controversial. This study analyzed the role of pelvic radiation therapy (RT) on the outcome in high-risk localized prostate cancer patients included in the Groupe d'Etude des Tumeurs Uro-Genitales (GETUG) 12 trial.. Patients with a nonpretreated high-risk localized prostate cancer and a staging lymphadenectomy were randomly assigned to receive either goserelin every 3 months for 3 years and 4 cycles of docetaxel plus estramustine or goserelin alone. Local therapy was administered 3 months after the start of systemic treatment. Performance of pelvic ENI was left to the treating physician. Only patients treated with primary RT were included in this analysis. The primary endpoint was biochemical progression-free survival (bPFS).. A total of 413 patients treated from 2002 to 2006 were included, of whom 358 were treated using primary RT. A total of 208 patients received pelvic RT and 150 prostate-only RT. Prostate-specific antigen (PSA) concentration, Gleason score, or T stage did not differ according to performance of pelvic RT; pN+ patients more frequently received pelvic RT than pN0 patients (P<.0001). Median follow-up was 8.8 years. In multivariate analysis, bPFS was negatively impacted by pN stage (hazard ratio [HR]: 2.52 [95% confidence interval [CI]: 1.78-3.54], P<.0001), Gleason score 8 or higher (HR: 1.41 [95% CI: 1.03-1.93], P=.033) and PSA higher than 20 ng/mL (HR: 1.41 [95% CI: 1.02-1.96], P=.038), and positively impacted by the use of chemotherapy (HR: 0.66 [95% CI: 0.48-0.9], P=.009). There was no association between bPFS and use of pelvic ENI in multivariate analysis (HR: 1.10 [95% CI: 0.78-1.55], P=.60), even when analysis was restricted to pN0 patients (HR: 0.88 [95% CI: 0.59-1.31], P=.53). Pelvic ENI was not associated with increased acute or late patient reported toxicity.. This unplanned analysis of a randomized trial failed to demonstrate a benefit of pelvic ENI on bPFS in high-risk localized prostate cancer patients.

Topics: Aged; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Confidence Intervals; Disease-Free Survival; Docetaxel; Estramustine; Goserelin; Humans; Lymph Node Excision; Lymphatic Irradiation; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Taxoids

Neoadjuvant androgen deprivation therapy (ADT) has been suggested to confer several clinical benefits in patients with prostate cancer (PCa) undergoing transperineal prostate brachytherapy (TPPB). Unlike gonadotropin-releasing hormone (GnRH) receptor agonists, a GnRH antagonist such as degarelix can achieve castrate levels of testosterone without testosterone flare. However, normalization of serum testosterone levels following completion of neoadjuvant ADT in either form of treatment has never been compared in clinical trials.. This is a single-center, open-label, randomized controlled study that will compare the efficacy and safety of degarelix with those of existing GnRH agonists combined with (125)I-TPPB. A total of 56 patients with low/intermediate-risk clinically localized PCa will be enrolled and randomized to one of two treatment groups: the GnRH agonist group and the degarelix group. Patients in the GnRH agonist group will receive leuprorelin acetate or goserelin acetate, and those in the degarelix group will receive the initial dose of 240 mg as 2 subcutaneous injections of 120 mg each, and then 80 mg of maintenance doses every 4 weeks for 12 weeks. Those randomly assigned to the 12-week intervention period will subsequently undergo 48-weeks of follow-up after (125)I-TPPB. The primary endpoint is defined as normalization of serum testosterone levels (>50 ng/dL) following completion of neoadjuvant ADT. All patients will be assessed every 4 weeks for the first 24 weeks, then every 12 weeks for the next 36 weeks after administrations of these drugs. Secondary endpoints are the proportion of normalized serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), the percent reduction in prostate specific antigen (PSA) compared with pretreatment levels, the percent reduction in total prostate volume (TPV) during neoadjuvant ADT, the percent increase in TPV after (125)I-TPPB, the percent reduction in hemoglobin, serum alkaline phosphatase (ALP), changes in free testosterone and bone mineral content measurement, the proportion of patients who have serum testosterone levels over 50 ng/dL at 12 weeks following completion of neoadjuvant ADT, and the improvement of quality of life (QOL).. The present study will provide additional insight regarding the benefit and potency of degarelix and will examine its potential as a new option for administration in neoadjuvant ADT.. Identification number: UMIN000015519 . Registration date: October 24, 2014.

Topics: Adult; Aged; Androgen Antagonists; Brachytherapy; Chemoradiotherapy; Gonadotropin-Releasing Hormone; Goserelin; Humans; Iodine Radioisotopes; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Oligopeptides; Prostatic Neoplasms; Research Design

This study was conducted to determine the efficacy of switching therapy with a second-line luteinizing hormone-releasing hormone (LHRH) analogue after prostate-specific antigen (PSA) progression for advanced prostate cancer. We enrolled 200 patients, from December 2005 to September 2013, with nodal positive, metastatic prostate cancer or disease progression after definite treatment receiving continuous LHRH analogue therapy with monthly depot leuprorelin(sc) acetate 3.75 mg/vial (LA) or goserelin acetate(sc) 3.6 mg/vial (GA). If the patients had castration-resistant prostate cancer, the treatment choice of switching therapy (from LA to GA or from GA to LA) prior to starting chemotherapy was given. The LH, testosterone level, and PSA change were recorded. The records showed that there were 127 patients receiving LA as initial ADT therapy, whereas the other 73 patients were in GA therapy. A total of 92 patients received LHRH analogue switching therapy (54 patients switched from LA to GA and 38 switched from GA to LA). The effect of LH and testosterone reduction prior to and after switching therapy was comparable between the two groups, and increased PSA level after 3 months of treatment was seen in both groups (median PSA: 15.7-67.7 ng/mL in the LA to GA group; 15.2-71.4 ng/mL in the GA to LA group). This study concluded that switching therapy for patients with PSA progression after ADT has no efficacy of further PSA response.

Topics: Aged; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

To assess total testosterone and prostatic-specific antigen (PSA) kinetics among diverse chemical castrations, advanced-stage prostate cancer patients were randomized into three groups of 20: Group 1, Leuprolide 3.75 mg; Group 2, Leuprolide 7.5 mg; and Group 3, Goserelin 3.6 mg. All groups were treated with monthly application of the respective drugs. The patients' levels of serum total testosterone and PSA were evaluated at two time periods: before the treatment and 3 months after the treatment. Spearman's rank correlation coefficient was utilized to verify the hypothesis of linear correlation between total testosterone and PSA levels. At the beginning the patients' age, stage, grade, PSA, and total testosterone were similar within the three groups, with median age 72, 70, and 70 years in Groups 1, 2, and 3, respectively. Three months after the treatment, patients who received Leuprolide 7.5 mg presented significantly lower median total testosterone levels compared with Goserelin 3.6 mg and Leuprolide 3.75 mg (9.5 ng/dL vs. 20.0 ng/dL vs. 30.0 ng/dL, respectively; p = .0072), while those who received Goserelin 3.6 mg presented significantly lower PSA levels compared with Leuprolide 7.5 mg and Leuprolide 3.75 mg (0.67 vs. 1.86 vs. 2.57, respectively; p = .0067). There was no linear correlation between total testosterone and PSA levels. Overall, regarding castration levels of total testosterone, 28.77% of patients did not obtain levels ≤50 ng/dL and 47.80% did not obtain levels ≤20 ng/dL. There was no correlation between total testosterone and PSA kinetics and no equivalence among different pharmacological castrations.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Dose-Response Relationship, Drug; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer.. Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks.. A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P < 0.001). Median time to biochemical progression for patients with serum bone-specific alkaline phosphatase level higher than 26 μg/L was 12.7 months. Multivariate analysis indicated that higher serum C-terminal telopeptide of type I collagen independently increased the risk of death (hazard ratio 9.62; 95 % confidence interval 2.11-43.89; P = 0.003). Median overall survival for patients with serum C-terminal telopeptide of type I collagen level higher than 8.0 ng/ml was 31.1 months.. Baseline bone markers can be useful as predictors for disease progression and survival time in patients with bone metastasis from treatment-naïve prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Neoplasms; Diphosphonates; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Therapy, Combination; Follow-Up Studies; Goserelin; Humans; Imidazoles; Japan; Male; Middle Aged; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Risk Factors; Survival Rate; Time Factors; Tosyl Compounds; Zoledronic Acid

To determine whether prolonged androgen suppression (AS) duration before radiotherapy improves survival and disease control in prostate cancer.. One thousand five hundred seventy-nine men with intermediate-risk prostate cancer were randomly assigned to 8 weeks of AS followed by radiotherapy with an additional 8 weeks of concurrent AS (16 weeks total) or to 28 weeks of AS followed by radiotherapy with an additional 8 weeks of AS (36 weeks total). The trial sought primarily to detect a 33% reduction in the hazard of prostate cancer death in the 28-week assignment. Time-to-event end points are reported for up to 10 years of follow-up.. There were no between-group differences in baseline characteristics of 1,489 eligible patients with follow-up. For the 8- and 28-week assignments, 10-year disease-specific survival rates were 95% (95% CI, 93.3% to 97.0%) and 96% (95% CI, 94.6% to 98.0%; hazard ratio [HR], 0.81; P = .45), respectively, and 10-year overall survival rates were 66% (95% CI, 62.0% to 69.9%) and 67% (95% CI, 63.0% to 70.8%; HR, 0.95; P = .62), respectively. For the 8- and 28-week assignments, 10-year cumulative incidences of locoregional progression were 6% (95% CI, 4.3% to 8.0%) and 4% (95% CI, 2.5% to 5.7%; HR, 0.65; P = .07), respectively; 10-year distant metastasis cumulative incidences were 6% (95% CI, 4.0% to 7.7%) and 6% (95% CI, 4.0% to 7.6%; HR, 1.07; P = .80), respectively; and 10-year prostate-specific antigen-based recurrence cumulative incidences were 27% (95% CI, 23.1% to 29.8%) and 27% (95% CI, 23.4% to 30.3%; HR, 0.97; P = .77), respectively.. Extending AS duration from 8 weeks to 28 weeks before radiotherapy did not improve outcomes. A lower than expected prostate cancer death rate reduced ability to detect a between-group difference in disease-specific survival. The schedule of 8 weeks of AS before radiotherapy plus 8 weeks of AS during radiotherapy remains a standard of care in intermediate-risk prostate cancer.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Disease-Free Survival; Flutamide; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy; Time Factors; Tosyl Compounds; Treatment Outcome

Optimizing androgen suppression may provide better control of localized prostate cancer (PCa). Numerous trials have supported the benefit of combining androgen deprivation therapy with definitive radiation therapy in men with locally advanced or high-grade disease. Addition of abiraterone to luteinizing hormone-releasing hormone agonist (LHRHa) with radiation has not been reported. We examined the safety of this combination as well as its impact on androgen suppression.. A prospective, phase 2 study was conducted in men with localized PCa treated with 6 months of neoadjuvant and concurrent abiraterone with LHRHa and radiation. Duration of adjuvant LHRHa was at the discretion of the treating clinician. Prostate biopsy assays were obtained prior to the start of therapy and prior to radiation. Sera and tissue androgen levels were measured by liquid chromatography-tandem mass spectrometry.. A total of 22 men with intermediate- (n=3) and high-risk PCa (n=19) received study therapy. Sixteen men completed the intended course of abiraterone, and 19 men completed planned radiation to 77.4 to 81 Gy. Radiation to pelvic nodes was administered in 20 men. The following grade 3 toxicities were reported: lymphopenia (14 patients), fatigue (1 patient), transaminitis (2 patients), hypertension (2 patients), and hypokalemia (1 patient). There were no grade 4 toxicities. All 21 men who complied with at least 3 months of abiraterone therapy had a preradiation prostate-specific antigen (PSA) concentration nadir of <0.3 ng/mL. Median levels of tissue androgen downstream of CYP17A were significantly suppressed after treatment with abiraterone, and upstream steroids were increased. At median follow-up of 21 months (range: 3-37 months), only 1 patient (who had discontinued abiraterone at 3 months) had biochemical relapse.. Addition of abiraterone to LHRHa with radiation is safe and achieves effective prostatic androgen suppression. Preliminary analysis of the clinical data is also promising, with excellent PSA nadir and no relapse to date in this high-risk population.

Topics: Androgen Antagonists; Androgens; Androstenes; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Neoadjuvant Therapy; Prednisone; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Time Factors

Androgen deprivation therapy (ADT) increases survival rates in prostate cancer (PCa) patients with locally advanced disease, but is associated with side effects that may impair daily function. Strength training may counteract several side effects of ADT, such as changes in body composition and physical functioning, which in turn may affect health-related quality of life (HRQOL). However, additional randomised controlled trials are needed to expand this knowledge.. Fifty-eight PCa patients on ADT were randomised to either 16 weeks of high-load strength training (n = 28) or usual care (n = 30). The primary outcome was change in total lean body mass (LBM) assessed by dual x-ray absorptiometry (DXA). Secondary outcomes were changes in regional LBM, fat mass, and areal bone mineral density (aBMD) measured by DXA; physical functioning assessed by 1-repetition maximum (1RM) tests, sit-to-stand test, stair climbing test and Shuttle walk test; and HRQOL as measured by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30.. No statistically significant effect of high-load strength training was demonstrated on total LBM (p = 0.16), but significant effects were found on LBM in the lower and upper extremities (0.49 kg, p < 0.01 and 0.15 kg, p < 0.05, respectively). Compared to usual care, high-load strength training showed no effect on fat mass, aBMD or HRQOL, but beneficial effects were observed in all 1RM tests, sit-to-stand test and stair climbing tests. Adherence to the training program was 88% for lower body exercises and 84% for upper body exercises. In summary, high-load strength training improved LBM in extremities and physical functioning, but had no effect on fat mass, aBMD, or HRQOL in PCa patients on ADT.

Topics: Absorptiometry, Photon; Adiposity; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Body Composition; Bone Density; Exercise Test; Goserelin; Humans; Lower Extremity; Male; Middle Aged; Muscle Strength; Patient Compliance; Prostatic Neoplasms; Quality of Life; Resistance Training; Surveys and Questionnaires; Upper Extremity; Walking

The efficacy of zoledronic acid in patients with treatment-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefits of combined zoledronic acid and androgen deprivation therapy in treatment-naïve prostate cancer with bone metastasis. The primary endpoint was skeletal-related event-free survival at 24 months.. Subjects were treatment-naïve patients with histologically confirmed adenocarcinoma of the prostate and radiological evidence of bone metastasis. Treatment consisted of bicalutamide 80 mg daily, goserelin acetate 10.8 mg every 12 weeks, and zoledronic acid 4 mg every 4 weeks. Zoledronic acid was continued for 24 months.. Of the patients enrolled between July 2008 and April 2010, 52 were included in the analyses. The median age of the patients was 72 years. The median baseline prostate-specific antigen level was 249.4 ng/mL. The median follow-up period was 33.3 months. The 24-month skeletal-related event-free survival rate was 84.4 % (95 % confidence interval 71.2-91.9). The median time to prostate-specific antigen progression was 25.9 months (95 % confidence interval 14.7-36.3). The median overall survival time was not reached. Improvement in pain or maintenance of no pain during the first 12 weeks was observed in 70 % of patients and the extent of bone disease was decreased in 10 % of patients at 12 months. Grade 3 osteonecrosis of the jaw was observed in three patients (5.8 %).. Zoledronic acid concomitant with androgen deprivation therapy as initial treatment in patients with treatment-naïve prostate cancer with bone metastasis resulted in an encouraging skeletal-related event-free survival rate at 24 months.

Topics: Aged; Androgen Antagonists; Androgens; Bone Neoplasms; Diphosphonates; Disease-Free Survival; Goserelin; Humans; Imidazoles; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Zoledronic Acid

Ligand-mediated activation of the androgen receptor (AR) is critical for prostate cancer (PCa) survival and proliferation. The failure to completely ablate tissue androgens may limit suppression of PCa growth. We evaluated combinations of CYP17A and 5-α-reductase inhibitors for reducing prostate androgen levels, AR signaling, and PCa volumes.. Thirty-five men with intermediate/high-risk clinically localized PCa were randomly assigned to goserelin combined with dutasteride (ZD), bicalutamide and dutasteride (ZBD), or bicalutamide, dutasteride, and ketoconazole (ZBDK) for 3 months before prostatectomy. Controls included patients receiving combined androgen blockade with luteinizing hormone-releasing hormone agonist and bicalutamide. The primary outcome measure was tissue dihydrotestosterone (DHT) concentration.. Prostate DHT levels were substantially lower in all experimental arms (0.02 to 0.04 ng/g v 0.92 ng/g in controls; P < .001). The ZBDK group demonstrated the greatest percentage decline in serum testosterone, androsterone, and dehydroepiandrosterone sulfate (P < .05 for all). Staining for AR and the androgen-regulated genes prostate-specific antigen and TMPRSS2 was strongly suppressed in benign glands and moderately in malignant glands (P < .05 for all). Two patients had pathologic complete response, and nine had ≤ 0.2 cm(3) of residual tumor (defined as a near-complete response), with the largest numbers of complete and near-complete responses in the ZBDK group.. Addition of androgen synthesis inhibitors lowers prostate androgens below that achieved with standard therapy, but significant AR signaling remains. Tissue-based analysis of steroids and AR signaling is critical to informing the search for optimal local and systemic control of high-risk prostate cancer.

Topics: 5-alpha Reductase Inhibitors; Aged; Aged, 80 and over; Androgen Antagonists; Androgen Receptor Antagonists; Androsterone; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Azasteroids; Biomarkers, Tumor; Chemotherapy, Adjuvant; Dihydrotestosterone; Dutasteride; Goserelin; Humans; Ketoconazole; Male; Middle Aged; Molecular Targeted Therapy; Neoadjuvant Therapy; Neoplasm Staging; Nitriles; Pilot Projects; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Signal Transduction; Steroid 17-alpha-Hydroxylase; Testosterone; Tosyl Compounds; Treatment Outcome

The aim of the study was to compare intermittent (IAD) and continuous (CAD) androgen deprivation therapy (ADT) between locally advanced (M0) and metastatic (M1) prostate cancer, and the effect of ADT on the quality of life.. In total, 852 men with advanced prostate cancer were enrolled to receive goserelin acetate for 24 weeks. Of these, 554 patients whose prostate-specific antigen (PSA) decreased to less than 10 ng/ml or by at least 50% (<20 ng/ml at baseline) were randomized to IAD or CAD. In the IAD arm, ADT was resumed for at least 24 weeks whenever PSA increased to greater than 20 ng/ml or above baseline.. Median follow-up time was 65 months. Median times from randomization to progression, death, prostate cancer death and treatment failure in M0 and M1 patients were 46.8 and 21.4, 57.6 and 40.3, 59.5 and 40.7, and 41.9 and 20.0 months, respectively (p < 0.001). No significant differences emerged between IAD and CAD. ADT showed a beneficial effect on pain, activity limitation and social functioning in M1 patients, and a deleterious effect on physical capacity in M0 patients and on sexual functioning in both groups. IAD offered extra benefit for activity limitation, social functioning and recovery of sexual functioning.. IAD is as efficient as CAD in treatment of locally advanced and metastatic prostate cancer. ADT improves quality of life in M1 patients, with IAD offering extra benefit.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease Progression; Disease-Free Survival; Follow-Up Studies; Goserelin; Health Status; Humans; Male; Neoplasm Metastasis; Pain Measurement; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Sexuality; Social Participation; Survival Rate; Time Factors

With great improvements in survival in patients with locally advanced prostate cancer, quality of life (QOL) is becoming an important factor in the selection of treatment. The aim of this study was to evaluate changes in health-related QOL in patients with locally advanced prostate cancer after intensity-modulated radiotherapy (IMRT) combined with androgen deprivation therapy. Patients were treated with IMRT combined with androgen deprivation. Total dose to the prostate was 68.2 Gy (2.2 Gy per fraction), and patients received 50 mg of oral Casodex once daily and 3.6 mg of subcutaneous Zoladex once every 28 days for 2.5 years. QOL was measured using the Expanded Prostate Cancer Index Composite. The time points were baseline, end of radiotherapy, and 3, 12, 36, 48, and 60 months after radiotherapy. From 2002 to 2007, a total of 87 patients were enrolled. Median follow-up time was 76.8 months. Compared with baseline, all four domain summary scores were decreased to varying degrees. Statistically significant changes in the urinary, bowel, and hormonal domain scores were observed (P < 0.05). The changes in scores for urinary incontinence and dysuria were -13.0 ± 8.3 and -6.12 ± 3.9, respectively (P < 0.05). QOL was decreased in patients with locally advanced prostate cancer after IMRT combined with androgen deprivation therapy in all four primary domains, especially in urinary, bowel, and hormonal domains. Nevertheless, the treatment was well tolerated in most patients during the 5 years of follow-up.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Goserelin; Humans; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Quality of Life; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Tosyl Compounds; Treatment Outcome; Urinary Incontinence

To evaluate long-term follow-up of a phase II trial of chemohormonal therapy in 62 men with prostate cancer biochemical relapse (BR).. Treatment was 4 cycles of docetaxel (70 mg/m(2)) every 3 weeks and estramustine 280 mg three times a day (days 1-5) followed by 15 months of goserelin acetate/bicalutamide. The primary endpoint was the proportion with prostate-specific antigen (PSA) <0.1 with recovered testosterone 5 years after completion of therapy. Secondary endpoints included time to progression (TTP), time to reinitiate androgen deprivation therapy (ADT), the proportion with castration-resistant prostate cancer (CRPC), and overall survival (OS).. Median follow-up was 8.6 years (range 1.3-11.1 years). At 5 year follow-up, 7 patients (11%) had PSA <0.1 (5 undetectable); 8 (13%) had PSA >0.1 but without reinitiation of ADT (median PSA 0.37). Of the 15 (24%) men without reinitiation of ADT, and 14 have recovered testosterone to normal range. Median TTP for the complete cohort was 35.0 months (95% confidence interval [CI] 31.7-39.2). Baseline PSA <3.0 ng/dL, no prior ADT, and prostatectomy (vs radiation) were associated with longer TTP (P = .0001, P = .0055, and P = .0398, respectively). At the time of analysis, 42 men (68%) had restarted ADT, 23 men had CRPC (37%), and 11 (18%) had chemotherapy. Median time to reinitiation of ADT was 32.6 months (range 0-107.6 months). Median OS has not been reached; there were 15 deaths.. Chemotherapy plus ADT for BR resulted in durable (>5 years) complete responses (<0.1 ng/mL) in 7 men (11%). Twenty-four percent of men have not re-initiated ADT 5 years from completion of protocol therapy.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Therapy, Combination; Estramustine; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Nitriles; Prostatic Neoplasms; Retrospective Studies; Taxoids; Time Factors; Tosyl Compounds; Treatment Outcome

Prostate cancer patients at increased risk for relapse after prostatectomy were treated in a neoadjuvant study with androgen deprivation therapy (ADT) in combination with cixutumumab, an inhibitory fully human monoclonal antibody against IGF receptor 1 (IGF-IR).. A clinical trial with prospective collection of serum and tissue was designed to test the potential clinical efficacy of neoadjuvant IGF-IR blockade combined with ADT in these patients. The effect of body mass index (BMI) on response of IGF-IR/insulin components to IGF-IR blockade was also examined.. Eligibility for the trial required the presence of high-risk prostate adenocarcinoma. Treatment consisted of bicalutamide, goserelin, and cixutumumab for 13 weeks before prostatectomy. Here we report on an analysis of serum samples from 29 enrolled patients. Changes in IGF and glucose homeostasis pathways were compared to control samples from patients in a concurrent clinical trial of neoadjuvant ADT alone.. Significant increases were seen in GH (P = .001), IGF-I (P < .0001), IGF-II (P = .003), IGF binding protein (IGFBP)-3 (P < .0001), C-peptide (P = .0038), and insulin (P = .05) compared to patients treated with ADT alone. IGFBP-1 levels were significantly lower in the cixutumumab plus ADT cohort (P = .001). No significant changes in blood glucose were evident. Patients with BMIs in the normal range had significantly higher GH (P < .05) and IGFBP-1 (P < 0.5) levels compared to overweight and obese patients.. Patients with IGF-IR blockade in combination with ADT demonstrated significant changes in IGF and glucose homeostasis pathway factors compared to patients receiving ADT alone. In the patients receiving combination therapy, patients with normal BMI had serum levels of glucose homeostasis components similar to individuals in the ADT-alone cohort, whereas patients with overweight and obese BMIs had serum levels that differed from the ADT cohort.

Topics: Adenocarcinoma; Androgen Antagonists; Anilides; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Body Mass Index; Cohort Studies; Goserelin; Humans; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 1; Male; Neoadjuvant Therapy; Nitriles; Obesity; Prostatectomy; Prostatic Neoplasms; Receptor, IGF Type 1; Risk; Secondary Prevention; Somatomedins; Tosyl Compounds; United States

To evaluate the feasibility of administering sunitinib in combination with androgen deprivation therapy and external-beam intensity modulated radiation therapy (XRT) in patients with localized high-risk prostate cancer.. Seventeen men with localized adenocarcinoma of the prostate with cT2c-cT4 or Gleason 8-10 or prostate-specific antigen >20 ng/mL received initial androgen deprivation (leuprolide 22.5 mg every 12 weeks plus oral bicalutamide 50 mg daily) for 4-8 weeks before oral sunitinib 12.5, 25, or 37.5 mg daily for 4 weeks as lead-in, then concurrently with and 4 weeks after XRT (75.6 Gy in 42 fractions to prostate and seminal vesicles). A 3+3 sequential dose-escalation design was used to assess the frequency of dose-limiting toxicity (DLT) and establish a maximal tolerated dose of sunitinib.. Sunitinib at 12.5- and 25-mg dose levels was well tolerated. The first 4 patients enrolled at 37.5 mg experienced a DLT during lead-in, and a drug interaction between sunitinib and bicalutamide was suspected. The protocol was revised and concurrent bicalutamide omitted. Of the next 3 patients enrolled at 37.5 mg, 2 of 3 receiving concurrent therapy experienced DLTs during radiation: grade 3 diarrhea and grade 3 proctitis, respectively. Only 1 of 7 patients completed sunitinib at 37.5 mg daily, whereas 3 of 3 patients (25 mg as starting dose) and 3 of 4 patients (25 mg as reduced dose) completed therapy.. The feasibility of combined vascular endothelial growth factor receptor (VEGFR)/platelet-derived growth factor receptor (PDGFR) inhibitor therapy, androgen deprivation, and radiation therapy for prostate cancer was established. Using a daily dosing regimen with lead-in, concurrent, and post-XRT therapy, the recommended phase 2 dose of sunitinib is 25 mg daily.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents; Combined Modality Therapy; Drug Interactions; Feasibility Studies; Goserelin; Humans; Indoles; Leuprolide; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Grading; Neoplasm Staging; Nitriles; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Pyrroles; Radiotherapy, Intensity-Modulated; Seminal Vesicles; Sunitinib; Tosyl Compounds

Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence.. Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization.. A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events.. Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Confidence Intervals; Drug Administration Schedule; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Neoplasm Metastasis; Nitriles; Penile Erection; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Survival Analysis; Tosyl Compounds

Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine men undergoing ADT for prostate cancer and ten healthy men with normal testosterone levels underwent 12 weeks of endurance training. Primary endpoints were insulin sensitivity (euglycemic-hyperinsulinemic clamps with concomitant glucose-tracer infusion) and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO2max (ml(O2)/min per kg) by 11 and 13% in the patients and controls respectively (P<0.0001). The patients and controls demonstrated an increase in peripheral tissue insulin sensitivity of 14 and 11% respectively (P<0.05), with no effect on hepatic insulin sensitivity (P=0.32). Muscle protein content of GLUT4 (SLC2A4) and total AKT (AKT1) was also increased in response to the training (P<0.05 and P<0.01 respectively). Body weight (P<0.0001) and whole-body fat mass (FM) (P<0.01) were reduced, while lean body mass (P=0.99) was unchanged. Additionally, reductions were observed in abdominal (P<0.01), subcutaneous (P<0.05), and visceral (P<0.01) FM amounts. The concentrations of plasma markers of systemic inflammation were unchanged in response to the training. No group × time interactions were observed, except for thigh intermuscular adipose tissue (IMAT) (P=0.01), reflecting a significant reduction in the amount of IMAT in the controls (P<0.05) not observed in the patients (P=0.64). In response to endurance training, ADT-treated prostate cancer patients exhibited improved insulin sensitivity and body composition to a similar degree as eugonadal men.

Topics: Aged; Antineoplastic Agents, Hormonal; Blood Glucose; Body Composition; Cholesterol, HDL; Exercise Therapy; Glucose Tolerance Test; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin Resistance; Male; Middle Aged; Physical Endurance; Prostatic Neoplasms; Testosterone

To assess the effects of timing and schedule of zoledronic acid (ZA) administration on bone mineral density (BMD) in patients beginning androgen deprivation therapy (ADT) for the treatment of recurrent prostate cancer.. In this randomized, 3-arm trial, we evaluated changes in BMD after 3 different ZA administration schedules in men with recurrent prostate cancer who were beginning ADT. Forty-four patients were enrolled and randomized to receive a single dose of ZA given 1 week before beginning ADT (arm 1), a single dose of ZA given 6 months after beginning ADT (arm 2), or monthly administration of ZA starting 6 months after beginning ADT, for a total of 6 doses (arm 3).. Patients who received ZA before ADT had a significant improvement in BMD at the total proximal femur and trochanter after 6 months compared with the other groups. In addition, only patients in the arm that received multiple doses improved lumbar spine BMD while on ADT, with these findings persisting to 24 months. However, this group also experienced more grade 1 adverse events.. Analysis of these data suggests that ZA administration before initiation of ADT was superior to treatment 6 months after starting ADT in maintaining BMD. In addition, monthly ZA administration can increase BMD above baseline but is associated with more adverse events. Further study is needed to examine whether the timing and frequency of ZA therapy in patients on ADT can reduce fracture risk.

Topics: Aged; Alkaline Phosphatase; Androgen Antagonists; Bone Density; Bone Density Conservation Agents; Cell Proliferation; Diphosphonates; Drug Administration Schedule; Goserelin; Humans; Imidazoles; Leuprolide; Lymphocyte Count; Male; Middle Aged; Osteoporosis; Prostate-Specific Antigen; Prostatic Neoplasms; T-Lymphocytes; Zoledronic Acid

We compared the efficacy and safety of 1- and 3-month depots of the luteinizing hormone-releasing hormone (LH-RH) agonist goserelin acetate in prostate cancer patients.. Patients were randomly assigned to the Direct Group that received the goserelin 3-month depot or the Switch Group that began with the 1-month depot for the first 3 months and then switched to the 3-month depot. All patients were co-administered the antiandrogen agent bicalutamide. Serum testosterone and prostate-specific antigen (PSA) levels and adverse events were recorded at weeks 4, 8, 12, and 24.. Baseline testosterone levels in the Direct and Switch Groups were 4.98 and 5.07 ng/mL, respectively (P = 0.798). At each week, the levels in both groups were ≤0.50 ng/mL (castration level) with no significant differences between them. All of the patients in the Switch Group and 98.1 % in the Direct Group had achieved castration levels at week 12, and 100 % had achieved such levels at week 24. Baseline PSA levels in the Direct and Switch Groups were 52.37 and 46.72 ng/mL, respectively (P = 0.793). Levels in both groups dropped continuously, to about 1.0 ng/mL at week 24, with no significant differences between the groups at any time. Three patients in the Direct Group experienced adverse events that were attributed to the co-administered bicalutamide.. There was no difference in the efficacy or safety between the 1- and 3-month depots of goserelin when given as initial prostate cancer treatment in combination with bicalutamide. Patients must be monitored for adverse events associated with bicalutamide.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Drug-Related Side Effects and Adverse Reactions; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms

Although endocrine therapy has been used for decades, its influence on the expression of microRNAs (miRNAs) in clinical tissue specimens has not been analyzed. Moreover, the effects of the TMPRSS2:ERG fusion on the expression of miRNAs in hormone naïve and endocrine-treated prostate cancers are poorly understood.. We used clinical material from a neoadjuvant trial consisting of 28 men treated with goserelin (n = 8), bicalutamide (n = 9), or no treatment (n = 11) for 3 months prior to radical prostatectomy. Freshly frozen specimens were used for microarray analysis of 723 human miRNAs. Specific miRNA expression in cancer, benign epithelium and stromal tissue compartments was predicted with an in silico Bayesian modeling tool.. The expression of 52, 44, and 34 miRNAs was affected >1.4-fold by the endocrine treatment in the cancer, non-malignant epithelium, and stromal compartments, respectively. Of the 52 miRNAs, only 10 were equally affected by the two treatment modalities in the cancer compartment. Twenty-six of the 52 genes (50%) showed AR binding sites in their proximity in either VCaP or LNCaP cell lines. Forty-seven miRNAs were differentially expressed in TMPRSS2:ERG fusion positive compared with fusion negative cases. Endocrine treatment reduced the differences between fusion positive and negative cases.. Goserelin treatment and bicalutamide treatment mostly affected the expression of different miRNAs. The effect clearly varied in different tissue compartments. TMPRSS2:ERG fusion positive and negative cases showed differential expression of miRNAs, and the difference was diminished by androgen ablation.

Topics: Adenocarcinoma; Anilides; Antineoplastic Agents; Computer Simulation; Gene Expression Regulation, Neoplastic; Gene Fusion; Goserelin; Humans; In Situ Hybridization, Fluorescence; Male; MicroRNAs; Neoadjuvant Therapy; Nitriles; Oligonucleotide Array Sequence Analysis; Oncogene Proteins, Fusion; Prostatectomy; Prostatic Neoplasms; Tosyl Compounds; Tumor Cells, Cultured

Intermittent dosing may reduce the adverse events (AEs) of androgen-deprivation therapy (ADT).. To compare intermittent androgen deprivation (IAD) and continuous androgen deprivation (CAD) with regard to health-related quality of life (QoL).. A total of 852 men with advanced prostate cancer (PCa) were enrolled to receive goserelin acetate 3.6 mg every 28 d for 24 wk. A total of 554 patients whose prostate-specific antigen (PSA) decreased to <10 ng/ml or by ≥50% (<20 ng/ml at baseline) were randomised to IAD or CAD.. In the IAD arm, ADT was resumed for at least 24 wk whenever PSA increased >20 ng/ml or above baseline.. QoL was monitored with a validated Cleary 30-item questionnaire and analysed by the Mann-Whitney U test, 0.5 standard deviation rule, and repeated measures analysis of variance. AEs and adverse drug reactions (ADRs) were analysed by the chi-square test.. Median follow-up was 65 mo. Significant differences in QoL emerged in activity limitation, physical capacity, and sexual functioning, favouring IAD. No significant differences emerged in the prevalence of AEs: 87 patients in the IAD arm (31.8%) and 95 in the CAD arm (33.9%) had cardiovascular (CV) AEs (p=0.59), with 25 (9.1%) and 29 (10.4%) withdrawn (p=0.62), and 21 (7.7%) and 24 (8.6%) dying because of a CV event (p=0.70), respectively; bone fractures occurred in 19 (6.9%) and 15 (5.4%) patients (p=0.44), respectively. Hot flushes or night sweats were the most common ADRs (47.1% vs 50.4%; p=0.44). Erectile dysfunction (15.7% vs 7.9%; p=0.042) and depressed mood (2.2 vs 0%; p=0.032) were more common in the IAD arm.. IAD showed benefits in the treatment of advanced PCa with respect to QoL. The prevalence of AEs was not significantly lower with IAD.. ClinicalTrials.gov, NCT00293670.

Topics: Aged; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chi-Square Distribution; Drug Administration Schedule; Finland; Goserelin; Humans; Kallikreins; Male; Neoplasm Grading; Neoplasm Staging; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Surveys and Questionnaires; Testosterone; Time Factors; Treatment Outcome

The treatment of intermediate- to high-risk prostate cancer with radical radiotherapy is usually in combination with neoadjuvant androgen deprivation therapy. The aim of the present trial was to investigate whether degarelix achieves comparable efficacy with that of goserelin plus bicalutamide as neoadjuvant therapy before radiotherapy.. The study was a randomised, parallel-arm, active-controlled, open-label trial in 244 men with a UICC prostate cancer TNM category T2b-T4, N0, M0, Gleason score ≥7, or prostate-specific antigen ≥10 ng/ml and a total prostate volume >30 ml, who were scheduled to undergo radical radiotherapy and in whom neoadjuvant androgen deprivation therapy was indicated. Eligible patients received treatment with either monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeks, the latter patients also receiving bicalutamide (50 mg) for 17 days initially. The primary efficacy measure was the mean percentage reduction in total prostate volume from baseline at week 12 measured by transrectal ultrasound. The severity and relief of lower urinary tract symptoms were assessed by the International Prostate Symptom Score questionnaire. Quality of life was assessed by the eighth question of the International Prostate Symptom Score. About 50% of the patients had moderate to severe lower urinary tract symptoms at baseline.. The total prostate volume decreased significantly from baseline to week 12 in both treatment groups, reaching -36.0 ± 14.5% in degarelix-treated patients and -35.3 ± 16.7% in goserelin-treated patients (adjusted difference: -0.3%; 95% confidence interval: -4.74; 4.14%). At the end of the therapy, more degarelix- than goserelin-treated patients reported International Prostate Symptom Score decreases of ≥3 points (37% versus 27%, P = 0.21). In addition, in patients with a baseline International Prostate Symptom Score of ≥13, the magnitude of the decrease was larger in degarelix- (n = 53) versus goserelin-treated patients (n = 17) (6.04 versus 3.41, P = 0.06).. The efficacy of degarelix in terms of prostate shrinkage is non-inferior to that of goserelin plus bicalutamide. The added benefits of degarelix in terms of more pronounced lower urinary tract symptom relief in symptomatic patients could be the reflection of differences in the direct effects on extra-pituitary receptors in the lower urinary tract [Clinicaltrials.gov ID: NCT00833248].

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Goserelin; Humans; Kallikreins; Male; Neoadjuvant Therapy; Nitriles; Oligopeptides; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Risk Factors; Testosterone; Tosyl Compounds

No studies to date have assessed the efficacy/tolerability of degarelix in the relief of lower urinary tract symptoms (LUTS) secondary to prostate cancer (PrCa).. Patients were randomised to degarelix 240/80 mg or goserelin 3.6 mg + bicalutamide flare protection (G+B); both treatments were administered for 3 months. The primary endpoint was change in International Prostate Symptom Score (IPSS) at week 12 compared with baseline.. This study was stopped early due to recruitment difficulties. 40 patients received treatment (degarelix n = 27; G+B n = 13); most had locally advanced disease and were highly symptomatic. Degarelix was non-inferior to G+B in reducing IPSS at week 12 in the full analysis set (p = 0.20); the significantly larger IPSS reduction in the per-protocol analysis (p = 0.04) was suggestive of superior reductions with degarelix. Significantly more degarelix patients had improved quality of life (IPSS question) at week 12 (85 vs. 46%; p = 0.01). Mean prostate size reductions at week 12 were 42 versus 25% for patients receiving degarelix versus G+B, respectively (p = 0.04; post hoc analysis). Most adverse events were mild/moderate; more degarelix patients experienced injection site reactions whereas more G+B patients had urinary tract infections/cystitis.. In 40 men with predominantly locally advanced PrCa and highly symptomatic LUTS, degarelix was at least non-inferior to G+B in reducing IPSS at week 12.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Androgen Antagonists; Anilides; Drug Therapy, Combination; Early Termination of Clinical Trials; Europe; Goserelin; Humans; Lower Urinary Tract Symptoms; Male; Middle Aged; Nitriles; Oligopeptides; Patient Selection; Prostatic Neoplasms; Sample Size; Time Factors; Tosyl Compounds; Treatment Outcome

Study Type - Therapy (prospective cohort). Level of Evidence 2a. What's known on the subject? and What does the study add? The sequential administration of a GnRH antagonist followed by an LHRH agonist in the management of prostate cancer patients has not been studied, but such a program would provide a more physiologic method of achieving testosterone suppression and avoid the obligatory testosterone surge and need for concomitant antiandrogens that accompany LHRH agonist therapy. The current study which uses abarelix initiation therapy for 12 weeks followed by either leuprolide or goserelin demonstrates the ability to more rapidly achieve testosterone suppression, avoid the obligatory LHRH induced testosterone surge, avoid the necessity of antiandrogens, all of which were accomplished safely, without inducing either additional or novel safety issues.. • To demonstrate the safety and endocrinological and biochemical efficacy of initiating treatment with the gonadotropin-releasing hormone (GnRH) antagonist, abarelix, followed by administration of an luteinizing hormone-releasing hormone (LHRH) agonist in patients with advanced and metastatic prostate cancer.. • A multicentre, open-label design study was conducted at 22 centres in the US involving patients with: localized, locally advanced or metastatic disease; with a rising prostate-specific antigen (PSA) after definitive local treatment; patients undergoing neoadjuvant hormonal therapy before local therapy (radical prostatectomy, radiation therapy or cryosurgery); and patients in whom intermittent therapy was the planned treatment. • All patients received abarelix for 12 weeks followed by an LHRH agonist (either leuprolide or goserelin) for 8 weeks • The primary efficacy endpoint was achievement and maintenance of castration defined as testosterone <50 ng/dL from day 29 through to day 141 and whether abarelix initiation therapy could eliminate the testosterone surge after two consecutive doses of LHRH agonist therapy. • PSA, LH and follicle-stimulating hormone (FSH) levels were measured and adverse events were monitored.. • A total of 176 patients were enrolled into the present study, the majority of whom had localized prostate cancer (82%) and a PSA level <10 ng/mL (62%). • At the end of the abarelix treatment period (day 85), 93.8% of patients achieved castrate levels; during the first week of switch over to the LHRH agonist therapy (days 85-92) the rate was 86.5% and during the week after the second LHRH agonist injection (days 114-12) it was 93.3%. • A small, transient increase in testosterone occurred during the first injection of the LHRH agonist; mean (standard deviation [sd]) values increased from 17 (17.8) ng/dL at day 85 to 37.3 (51.07) ng/dL at day 86. • Mean (sd) PSA levels decreased from 20.5 (56.6) ng/mL at baseline to 3.7 (23.5) ng/mL on day 85 and remained stable throughout the LHRH agonist treatment phase. • Treatment-related adverse events occurred in 84% of patients overall; a similar incidence was reported during the two treatment phases.. • Abarelix initiation therapy results in the desired effect of achieving rapid testosterone suppression; testosterone surges after subsequent LHRH agonist therapy are greatly abrogated or completely eliminated. • This treatment paradigm (abarelix initiation followed by agonist maintenance) obviates the need for an antiandrogen. • Abarelix was well tolerated and no clinically meaningful or novel adverse events were observed during abarelix treatment or in the transition to LHRH agonist maintenance therapy.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Goserelin; Humans; Leuprolide; Male; Middle Aged; Oligopeptides; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; United States

We report a Phase II trial assessing the acute and late toxicities of intensity-modulated radiation therapy (IMRT), long-term androgen suppression (LTAS), and bevacizumab in patients with high-risk localized prostate cancer.. We treated 18 patients with LTAS with bicalutamide and goserelin in combination with bevacizumab and IMRT. Bevacizumab (10 mg/kg every 2 weeks) was administered for the first 16 weeks, and 15 mg/kg was then given every 3 weeks for 12 additional weeks, with an IMRT dose of 77.9 Gy to the prostate, 64.6 Gy to the seminal vesicles, and 57 Gy to the pelvic lymph nodes. Patients were eligible if they had clinical stage T2b to T4, a Gleason sum score of 8 to 10, or a prostate- specific antigen level of 20ng/mL or greater. The primary endpoint of the study was evaluation of acute and late toxicities.. The median age was 69 years, with a median pretreatment prostate-specific antigen level of 12.5 ng/mL and Gleason score of 8. The pretreatment clinical stage was T1c in 4 patients, T2 in 11, and T3 in 3. All patients completed IMRT with median follow-up of 34 months (range, 28-40 months) The most common Grade 2 or higher toxicities were hypertension (61% of patients with Grade 2 and 11% with Grade 3), proteinuria (28% with Grade 2 and 6% with Grade 3), and leucopenia (28% with Grade 2). No Grade 4 or higher acute toxicities were reported. Late toxicities included proctitis (6% of patients with Grade 2 and 11% with Grade 3), rectal bleeding (6% with Grade 2 and 11% with Grade 3), hematuria (6% with Grade 2), proteinuria (17% with Grade 2), hyponatremia (6% with Grade 3), cystitis (6% with Grade 3), and urinary retention (6% with Grade 2 and 11% with Grade 3). Grade 4 prostatitis occurred in 1 patient (6%).. Bevacizumab does not appear to exacerbate the acute effects of IMRT. Late toxicities may have been worsened with this regimen. Further investigations of bevacizumab with LTAS and IMRT should be performed cautiously.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Drug Administration Schedule; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Nitriles; Pilot Projects; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Risk; Tosyl Compounds

To evaluate the relative efficiency of leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg in relation to the reduction in serum testosterone, regarding the levels of castration.. We evaluated prospectively 60 randomized patients with advanced prostate carcinoma, with indication for hormone blockade. The patients were divided into 3 groups of 20: Group (1) received leuprolide 3.75 mg; Group (2) received leuprolide 7.5 mg; and Group (3) received goserelin 3.6 mg. All groups were treated with monthly application of the respective drugs. The patients' levels of serum testosterone were evaluated in two moments: before the treatment and 3 months after the treatment.. The patients' ages were similar within the three groups, with a median of 72, 70, and 70 in groups 1, 2, and 3, respectively. Of the patients that received leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg, 26.3, 25, and 35%, respectively, did not reach castration levels, considering a testosterone cutoff ≤ 50 ng/dl. And 68.4, 30, and 45%, respectively, did not reach castration levels, considering a testosterone cutoff ≤ 20 ng/dl.. There were no statistically significant differences in the levels of castration when comparing leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg, altogether. When compared in groups of two, there was a statistically significant difference between leuprolide 3.75 mg and leuprolide 7.5 mg, the latter presented better results in reaching castration levels, cutoff ≤ 20 ng/dl. The importance of this difference, however, must be measured with caution, since the comparison of the three groups simultaneously did not reach the established significance level, even though it came close.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Dose-Response Relationship, Drug; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

To update the results with 10-year data of a phase II prospective trial of neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy for locally advanced prostate cancer (SWOG 9109). The optimal management for clinical stage T3 and T4 N0,M0 prostate cancer is uncertain.. Sixty-two patients with clinical stage T3 and T4 N0,M0 prostate cancer were enrolled. Cases were classified by stage T3 vs T4 and by volume of disease (bulky >4 cm and nonbulky ≤ 4 cm).. Fifty-five of 61 eligible patients completed the trial with radical prostatectomy after neoadjuvant androgen deprivation therapy (ADT). The median preoperative prostate-specific antigen value was 19.8 ng/mL, and 67% of patients had a Gleason score of ≥ 7. Among 41 patients last known to be alive, median follow-up is 10.6 years (range 5.1-12.6). In all, 38 patients have had disease progression (30/55, 55%) or died without progression (8/55, 15%) for a 10-year progression-free survival (PFS) estimate of 40% (95% CI 27-53). Median PFS was 7.5 years, and median survival has not been reached. The 10-year overall survival (OS) estimate is 68% (95% CI 56-80).. In this small, prospective phase II study, neoadjuvant hormonal therapy with goserelin acetate and flutamide followed by radical prostatectomy achieves long-term PFS and OS comparable with alternative treatments. This approach is feasible and may be an alternative to a strategy of combined radiation and ADT.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease Progression; Drug Therapy, Combination; Flutamide; Follow-Up Studies; Goserelin; Humans; Infusions, Subcutaneous; Kaplan-Meier Estimate; Male; Middle Aged; Neoadjuvant Therapy; Prospective Studies; Prostatic Neoplasms; Treatment Outcome

Endocrine therapy by castration or anti-androgens is the gold standard treatment for advanced prostate cancer. Although it has been used for decades, the molecular consequences of androgen deprivation are incompletely known and biomarkers of its resistance are lacking. In this study, we studied the molecular mechanisms of hormonal therapy by comparing the effect of bicalutamide (anti-androgen), goserelin (GnRH agonist) and no therapy, followed by radical prostatectomy. For this purpose, 28 men were randomly assigned to treatment groups. Freshly frozen specimens were used for gene expression profiling for all known protein-coding genes. An in silico Bayesian modelling tool was used to assess cancer-specific gene expression from heterogeneous tissue specimens. The expression of 128 genes was > two-fold reduced by the treatments. Only 16% of the altered genes were common in both treatment groups. Of the 128 genes, only 24 were directly androgen-regulated genes, according to re-analysis of previous data on gene expression, androgen receptor-binding sites and histone modifications in prostate cancer cell line models. The tumours containing TMPRSS2-ERG fusion showed higher gene expression of genes related to proliferation compared to the fusion-negative tumours in untreated cases. Interestingly, endocrine therapy reduced the expression of one-half of these genes and thus diminished the differences between the fusion-positive and -negative samples. This study reports the significantly different effects of an anti-androgen and a GnRH agonist on gene expression in prostate cancer cells. TMPRSS2-ERG fusion seems to bring many proliferation-related genes under androgen regulation.

Topics: Administration, Oral; Analysis of Variance; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Bayes Theorem; Castration; Chemotherapy, Adjuvant; Chi-Square Distribution; Finland; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Subcutaneous; Male; Neoadjuvant Therapy; Neoplasms, Hormone-Dependent; Nitriles; Oligonucleotide Array Sequence Analysis; Oncogene Proteins, Fusion; Prostatectomy; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

Study Type--Therapy (RCT) Level of Evidence 1b. What's known on the subject? and What does the study add? Androgen deprivation therapy (ADT) is commonly used as a primary treatment for patients with prostate cancer (PCa) who are not eligible for radical treatment options. ADT is also used in patients with PCa as neo-adjuvant hormone therapy to reduce prostate volume and down-stage the disease before radiotherapy with curative intent. The present study showed that ADT with the gonadotropin hormone-releasing hormone (GhRH) antagonist degarelix is non-inferior to combined treatment with the LHRH agonist goserelin and bicalutamide in terms of reducing prostate volume during the treatment period of 3 months. Degarelix treatment evokes, however, significantly better relief of lower urinary tract symptoms in patients having moderate and severe voiding problems.. • To assess the efficacy of monthly degarelix treatment for reduction of total prostate volume (TPV), relief of lower urinary tract symptoms (LUTS) and improvement of quality of life (QoL) in patients with prostate cancer (PCa) using monthly goserelin as active control.. • This was a randomized, parallel-arm, active-controlled, open-label, multicentre trial on 182 patients treated with either monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeks. • For flare protection, goserelin-treated patients also received daily bicalutamide (50 mg) during the initial 28 days. • Key trial variables monitored monthly were TPV (primary endpoint), serum testosterone, prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS) and the Benign Prostate Hyperplasia Impact Index.. • In all, 175 patients completed the trial (96.1%). • At week 12, changes in TPV for degarelix and goserelin were similar (-37.2% vs -39.0%) and met the predefined non-inferiority criterion. • Decreases in IPSS were greater in degarelix than in goserelin-treated patients, differences being statistically significant in patients with baseline IPSS > 13 (-6.7 ± 1.8 vs -4.0 ± 1.0; P = 0.02). • The number of patients with an IPSS change of ≥ 3 over baseline was also significantly higher in patients treated with degarelix (61.0 vs 44.3%, P = 0.02). • Both treatments were safe and well tolerated.. • Medical castration reduces TPV and could also improve LUTS in patients with PCa. • While the short-term efficacy of degarelix and goserelin + bicalutamide was the same in terms of TPV reduction, degarelix showed superiority in LUTS relief in symptomatic patients, which could highlight the different actions of these drugs on extrapituitary gonadotrophin-releasing hormone (GnRH) receptors in the bladder and/or the prostate.

Topics: Aged; Analysis of Variance; Androgen Antagonists; Anilides; Antineoplastic Combined Chemotherapy Protocols; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lower Urinary Tract Symptoms; Male; Nitriles; Oligopeptides; Prostatic Neoplasms; Quality of Life; Tosyl Compounds; Treatment Outcome; Tumor Burden

The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant androgen deprivation therapy (NADT) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer. Here we report the 10-year results.. Between June, 1996, and February, 2000, 818 men with T2b, T2c, T3, and T4 N0 M0 prostate cancers were randomly assigned to receive radiotherapy alone, 3 months of NADT plus radiotherapy, or 6 months of NADT plus radiotherapy. The radiotherapy dose for all groups was 66 Gy, delivered to the prostate and seminal vesicles (excluding pelvic nodes) in 33 fractions of 2 Gy per day (excluding weekends) over 6·5-7·0 weeks. NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day. NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group. Primary endpoints were prostate-cancer-specific mortality and all-cause mortality. Treatment allocation was open label and randomisation was done with a minimisation technique according to age, clinical stage, tumour grade, and initial prostate-specific antigen concentration (PSA). Analysis was by intention-to-treat. The trial has been closed to follow-up and all main endpoint analyses are completed. The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000237482.. 802 men were eligible for analysis (270 in the radiotherapy alone group, 265 in the 3-month NADT group, and 267 in the 6-month NADT group) after a median follow-up of 10·6 years (IQR 6·9-11·6). Compared with radiotherapy alone, 3 months of NADT decreased the cumulative incidence of PSA progression (adjusted hazard ratio 0·72, 95% CI 0·57-0·90; p=0·003) and local progression (0·49, 0·33-0·73; p=0·0005), and improved event-free survival (0·63, 0·52-0·77; p<0·0001). 6 months of NADT further reduced PSA progression (0·57, 0·46-0·72; p<0·0001) and local progression (0·45, 0·30-0·66; p=0·0001), and led to a greater improvement in event-free survival (0·51, 0·42-0·61, p<0·0001), compared with radiotherapy alone. 3-month NADT had no effect on distant progression (0·89, 0·60-1·31; p=0·550), prostate cancer-specific mortality (0·86, 0·60-1·23; p=0·398), or all-cause mortality (0·84, 0·65-1·08; p=0·180), compared with radiotherapy alone. By contrast, 6-month NADT decreased distant progression (0·49, 0·31-0·76; p=0·001), prostate cancer-specific mortality (0·49, 0·32-0·74; p=0·0008), and all-cause mortality (0·63, 0·48-0·83; p=0·0008), compared with radiotherapy alone. Treatment-related morbidity was not increased with NADT within the first 5 years after randomisation.. 6 months of neoadjuvant androgen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer, particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged androgen deprivation.. Australian Government National Health and Medical Research Council, Hunter Medical Research Institute, AstraZeneca, and Schering-Plough.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Australia; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Flutamide; Follow-Up Studies; Goserelin; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; New Zealand; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Time Factors; Treatment Outcome

Men with high-risk features (extraprostatic extension or high Gleason grade) face a high risk of prostate cancer recurrence after radical prostatectomy. Clinical trials of adjuvant systemic therapy for such patients have been limited.. The SWOG (Southwest Oncology Group) S9921 study randomly assigned 983 men with high-risk features at prostatectomy to receive adjuvant therapy with androgen deprivation (ADT) alone or in combination with mitoxantrone chemotherapy. ADT consisted of goserelin and bicalutamide for 2 years.. Although the final primary treatment comparison results are not ready for publication, this article reports results in the ADT-alone control arm with a median follow-up of 4.4 years. For these 481 men, the estimated 5-year biochemical failure-free survival is 92.5% (95% CI, 90 to 95), and 5-year overall survival is 95.9% (95% CI, 93.9 to 97.9).. The results of this trial, taken in context, make a compelling argument for counseling all high-risk patients with prostate cancer about adjuvant ADT. This article discusses the challenges in the design and implementation of clinical trials to take the next step forward in adjuvant therapy for prostate cancer because of the excellent survival achieved with currently available therapies and highlights the need for better molecular markers to personalize care.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Goserelin; Humans; Male; Middle Aged; Mitoxantrone; Nitriles; Prostatectomy; Prostatic Neoplasms; Tosyl Compounds

It is not known whether short-term androgen-deprivation therapy (ADT) before and during radiotherapy improves cancer control and overall survival among patients with early, localized prostate adenocarcinoma.. From 1994 through 2001, we randomly assigned 1979 eligible patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level of 20 ng per milliliter or less to radiotherapy alone (992 patients) or radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy (radiotherapy plus short-term ADT, 987 patients). The primary end point was overall survival. Secondary end points included disease-specific mortality, distant metastases, biochemical failure (an increasing level of PSA), and the rate of positive findings on repeat prostate biopsy at 2 years.. The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiation-induced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients, with no significant reductions among low-risk patients.. Among patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less, the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival. According to post hoc risk analysis, the benefit was mainly seen in intermediate-risk, but not low-risk, men. (Funded by the National Cancer Institute; RTOG 94-08 ClinicalTrials.gov number, NCT00002597.).

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Erectile Dysfunction; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Multivariate Analysis; Prostate; Prostatic Neoplasms; Radiotherapy; Radiotherapy Dosage; Risk; Survival Rate

To ascertain whether biochemical response to neoadjuvant androgen-deprivation therapy (ADT) before radiotherapy (RT), rather than duration, is the critical determinant of benefit in the multimodal treatment of localized prostate cancer, by comparing outcomes of subjects from the Canadian multicenter 3- vs 8-month trial with a pre-RT, post-hormone PSA (PRPH-PSA) < or =0.1 ng/ml vs those >0.1 ng/ml.. From 1995 to 2001, 378 men with localized prostate cancer were randomized to 3 or 8 months of neoadjuvant ADT before RT. On univariate analysis, survival indices were compared between those with a PRPH-PSA < or =0.1 ng/ml vs >0.1 ng/ml, for all patients and subgroups, including treatment arm, risk group, and gleason Score. Multivariate analysis identified independent predictors of outcome.. Biochemical disease-free survival (bDFS) was significantly higher for those with a PRPH-PSA < or =0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (55.3% vs 49.4%, p = 0.014). No difference in survival indices was observed between treatment arms. There was no difference in bDFS between patients in the 3- and 8-month arms with a PRPH-PSA < or =0.1 ng/ml nor those with PRPH-PSA >0.1 ng/ml. bDFS was significantly higher for high-risk patients with PRPH-PSA < or =0.1 ng/ml compared with PRPH-PSA >0.1 ng/ml (57.0% vs 29.4%, p = 0.017). Multivariate analysis identified PRPH-PSA (p = 0.041), Gleason score (p = 0.001), initial PSA (p = 0.025), and T-stage (p = 0.003), not ADT duration, as independent predictors of outcome.. Biochemical response to neoadjuvant ADT before RT, not duration, appears to be the critical determinant of benefit in the setting of combined therapy. Individually tailored ADT duration based on PRPH-PSA would maximize therapeutic gain, while minimizing the duration of ADT and its related toxicities.

Topics: Adenocarcinoma; Aged; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease-Free Survival; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors

To report our long-term follow-up of an institutional randomized prospective trial of radical prostatectomy (RP) with or without a 3-month course of neoadjuvant hormone therapy (NHT), which results in pathological downstaging, but generally no reduction in biochemical recurrence (BCR) on early follow-up (at 3 years).. From December 1992 to June 1996, 148 patients with clinically localized prostate cancer were randomized to RP only or 3 months of goserelin acetate and flutamide before RP. BCR was defined as a detectable serum prostate specific antigen level (>0.1 ng/mL) at least 6 weeks after surgery, with a confirmatory increase.. The median follow-up for BCR-free patients was 8 years. There was no significant difference in BCR-free probabilities between groups (P = 0.7). The BCR-free probability at 7 years was 78% for patients undergoing RP only and 80% for patients undergoing NHT and RP (difference of 2%; 95% confidence interval, CI, 12-16%). A Cox regression showed no significant relationship between NHT and BCR (hazard ratio 1.16; 95% CI, 0.56-2.39, P = 0.7). Overall, two patients had local recurrence and six developed metastases, and were evenly distributed among the RP only and NHT groups.. Although our study was not originally powered to detect differences in BCR, there was no overall benefit in BCR-free probability, local recurrence or metastasis with 3 months of NHT at 8 years of follow-up. Pending evidence of improvement in patient outcomes, NHT before RP appears to be unjustified outside of clinical trials.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Epidemiologic Methods; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prostatectomy; Prostatic Neoplasms; Treatment Outcome

The effects of testosterone (T) and estradiol (E(2)) on cognition in men are confounded in extant studies. This randomized, placebo-controlled trial was undertaken to investigate the possible effects of E(2) on cognition in older men. Twenty-five men with prostate cancer (mean age: 71.0+/-8.8 years) who required combined androgen blockade treatment were enrolled. Performance on cognitive tests was evaluated at pre-treatment baseline and following 12 weeks of treatment with a gonadotropin-releasing hormone analog and the nonsteroidal antiandrogen bicalutamide to determine whether specific cognitive functions would decline when the production of both T and E(2) were suppressed. In the second phase of the study, either micronized E(2) 1mg/day or an oral daily placebo was randomly added to the combined androgen blockade for an additional 12 weeks to determine whether E(2) would enhance performance in specific cognitive domains (verbal memory, spatial ability, visuomotor abilities and working memory). Compared to pretreatment, no differences in scores occurred on any cognitive test following 12 weeks of combined androgen blockade. In the add-back phase of the study (Visit 3), the placebo-treated men, but not the E(2)-treated men, exhibited a trend towards improvement in their scores on both the immediate (p=.075) and delayed recall (p=.095) portions of a verbal memory task compared to baseline. Moreover, at Visit 3, placebo-treated men performed significantly better than the E(2)-treated men on both the immediate (p=.020) and delayed recall (p=.016) portions of the verbal memory task. Thus, combined androgen blockade plus add-back E(2) failed to improve short- or long-term verbal memory performance in this sample of older men being treated for prostate cancer.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cognition; Drug Administration Schedule; Estradiol; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Neuropsychological Tests; Nitriles; Placebos; Prostatic Neoplasms; Tosyl Compounds

Although androgen deprivation therapy (ADT) has been associated with bone loss in patients with prostate cancer, its mechanism remains unclear. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/parathyroid hormone (PTH) axis plays a critical role in bone synthesis, but its activity during ADT is also unknown.. Seventy-one patients with localized prostate cancer, who received ADT, were prospectively studied based on their bone mineral density (BMD) and blood and urine samples at the baseline and after ADT for 6 months.. The IGF-1 level was correlated with BMD before ADT (rs = 0.325, P = 0.007), but such a relationship disappeared after ADT (P = 0.565). Following ADT, the serum IGF-1 level increased compared with that at the baseline (22 +/- 6 nmol/L vs. 19 +/- 5 nmol/L, respectively, P < 0.001). The serum PTH level was reduced after ADT (41 +/- 33 ng/L) compared with the baseline (55 +/- 44 ng/L) (P < 0.001), but no change was observed in the serum GH level (P = 0.691). Bone resorption markers such as blood N-telopeptide (NTx), urinary NTx, calcium, and inorganic phosphorus levels increased after ADT (P < 0.001 in all). The ratio of the IGF-1 level after ADT/before ADT was associated with the ratio of the value after ADT/before ADT of alkaline phosphatase (rs = 0.266, P = 0.025) and calcium (rs = 0.242, P = 0.042).. Despite the unaffected GH and upregulated bone resorption, the serum IGF-1 level was elevated by ADT. The IGF-1 level was correlated with BMD before ADT, but the relationship was disrupted after ADT. IGF-1 or its receptor in the bone may be functionally inactivated during ADT.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Density; Bone Diseases, Metabolic; Flutamide; Goserelin; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Orchiectomy; Parathyroid Hormone; Prospective Studies; Prostatic Neoplasms

Radiation Therapy Oncology Group 85-31 was a randomized trial comparing radiotherapy (RT) alone vs. RT plus adjuvant androgen suppression for life in unfavorable-prognosis carcinoma of the prostate. We examined the impact of early initiation of salvage hormonal therapy (HT) in relapsing patients randomized to RT alone arm.. Patients were divided into two groups: early salvage HT and late salvage HT. The early salvage group was defined as receiving HT with a prostate-specific antigen (PSA) level of less than 10 ng/mL, and the late salvage HT group had a PSA level of 10 ng/mL or greater. The outcomes were overall survival (OS), cause-specific mortality (CSM), and local failure (LF). The Kaplan-Meier estimation and log-rank test were used for OS, and the cumulative incidence estimation and Gray's test were used for CSM and LF. Proportional hazards regression models were used to compare the outcomes adjusted for other covariates.. The median follow-up times of surviving patients in the early and late salvage HT groups were about 11 and 13 years, respectively. The late salvage HT group had significantly more post-prostatectomy patients and patients with high Gleason scores. After adjustment for all covariates, OS was significantly longer in the early salvage HT group (hazard ratio, 1.5; p = 0.01). However, there were no statistically significant differences in LF or CSM between the groups.. The early introduction of salvage HT resulted in improved OS but not improved CSM and LF. A randomized trial to define the optimal salvage hormonal timing is warranted in this group of patients with PSA recurrence after RT.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cause of Death; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Reference Values; Salvage Therapy; Survival Analysis; Time Factors

To evaluate the effect of zoledronic acid on androgen deprivation therapy in patients with hormone-sensitive prostate cancer by measuring the percentage change in lumbar-spine bone mineral density (BMD) at 12 and 24 months.. An open-label, multicenter, randomized, two-phase study was conducted in patients with hormone-sensitive prostate cancer (N = 200) receiving 10.8 mg goserelin acetate with or without zoledronic acid (4 mg intravenously) every 3 months. In phase I, patients were randomized to goserelin acetate alone or goserelin acetate plus zoledronic acid for 12 months. In phase II, patients receiving goserelin acetate plus zoledronic acid continued treatment for up to a total of 24 months, whereas patients receiving goserelin acetate alone were randomized to goserelin acetate alone or goserelin acetate plus zoledronic acid for an additional 12 months. Lumbar-spine, femoral-neck, and total-hip BMD were assessed at 6, 12, and 24 months. Additional assessments included height change, laboratory studies, bone scans, radiographs, and computed tomography scans.. Significant BMD differences between patients receiving goserelin acetate alone and goserelin acetate plus zoledronic acid were observed at the 12-month (p

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Density; Bone Density Conservation Agents; Diphosphonates; Goserelin; Humans; Imidazoles; Male; Middle Aged; Prostatic Neoplasms; Time Factors; Zoledronic Acid

We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results.. For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1-2 prostatic adenocarcinoma with WHO histological grade 3 or T3-4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0-2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082.. Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1-12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3-29·7) in the radiotherapy-alone group and 47·7% (39·0-56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33-0·55, p<0·0001). 10-year overall survival was 39·8% (95% CI 31·9-47·5) in patients receiving radiotherapy alone and 58·1% (49·2-66·0) in those allocated combined treatment (HR 0·60, 95% CI 0·45-0·80, p=0·0004), and 10-year prostate-cancer mortality was 30·4% (95% CI 23·2-37·5) and 10·3% (5·1-15·4), respectively (HR 0·38, 95% CI 0·24-0·60, p<0·0001). No significant difference in cardiovascular mortality was noted between treatment groups both in patients who had cardiovascular problems at study entry (eight of 53 patients in the combined treatment group had a cardiovascular-related cause of death vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment.. In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Canada; Cardiovascular Diseases; Chemotherapy, Adjuvant; Cyproterone Acetate; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Europe; Fractures, Bone; Goserelin; Humans; Israel; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Neoplasm Staging; Prostatic Neoplasms; Risk Assessment; Russia; Time Factors; Treatment Outcome

To evaluate the effect of 3 vs. 8 months of neoadjuvant hormonal therapy before conventional-dose radiotherapy (RT) on disease-free survival for localized prostate cancer.. Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before 66 Gy RT at four participating centers. The median baseline prostate-specific antigen level was 9.7 ng/mL (range, 1.3-189). Of the 378 men, 26% had low-, 43% intermediate-, and 31% high-risk disease. The two arms were balanced in terms of age, Gleason score, clinical T category, risk group, and presenting prostate-specific antigen level. The median follow-up for living patients was 6.6 years (range, 1.6-10.1). Of the 378 patients, 361 were evaluable, and 290 were still living.. The 5-year actuarial freedom from failure rate for the 3- vs. 8-month arms was 72% vs. 75%, respectively (p = 0.18). No difference was found in the failure types between the two arms. The median prostate-specific antigen level at the last follow-up visit for patients without treatment failure was 0.6 ng/mL in the 3-month arm vs. 0.50 ng/mL in the 8-month arm. The disease-free survival rate at 5 years was improved for the high-risk patients in the 8-month arm (71% vs. 42%, p = 0.01).. A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Canada; Disease-Free Survival; Drug Administration Schedule; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate

Gonadotropin-releasing hormone (GnRH) agonists are associated with greater risk of coronary heart disease and myocardial infarction in men with prostate cancer, but little is known about potential impact on cardiovascular mortality. We assessed the relationship between GnRH agonists and cardiovascular mortality in a large randomized phase III trial of men treated with or without adjuvant goserelin after radiation therapy (RT) for locally advanced prostate cancer.. Between 1987 and 1992, 945 men with locally advanced prostate cancer were randomly assigned to RT and adjuvant goserelin or RT alone. Fine and Gray's regression was used to evaluate treatment effect on cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus (DM), body mass index, race, Gleason score, stage, acid phosphatase level, prostatectomy history, and nodal involvement.. After a median follow-up of 8.1 years, there were 117 cardiovascular-related deaths but no treatment-related increase in cardiovascular mortality. At 9 years, cardiovascular mortality for men receiving adjuvant goserelin was 8.4% v 11.4% for men treated without adjuvant goserelin (Gray's P = .17). In multiple regression analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR] = 0.73; 95% CI, 0.47 to 1.15; P = .16; when censoring at time of salvage goserelin therapy, HR = 0.99; 95% CI, 0.58 to 1.69; P = .97). Traditional cardiac risk factors, including prevalent CVD and DM, were significantly associated with greater cardiovascular mortality.. GnRH agonists do not seem to increase cardiovascular mortality in men with locally advanced prostate cancer. Further studies are warranted to evaluate adverse effects of GnRH agonists in men with lower cancer-specific mortality.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Regression Analysis

The objective of this study was to evaluate the predictive value of prostate biopsies that were obtained 24 months after the completion of radiotherapy (RT) with respect to disease-free survival (DFS) in a randomized trial that compared 3 months versus 8 months of neoadjuvant hormone therapy before conventional dose external RT.. From February 1995 to June 2001, 378 men were randomized to receive either 3 months or 8 months of combined flutamide and goserelin before they received 66 Gray of RT at 4 participating centers. By risk group, 26% of patients were categorized as low risk, 43% were categorized as intermediate risk, and 31% were categorized as high risk. The 2 treatment arms were balanced in terms of age, Gleason score, clinical tumor classification, risk group, and presenting prostate-specific antigen level. The median follow-up for the patients who remained alive was 6.6 years (range, 1.6-10.1 years). Of 361 evaluable patients, 290 patients remained alive. Post-RT prostate biopsies were performed between 24 and 30 months after the completion of RT in 3 of the 4 centers. Biopsies that had residual tumor with severe treatment effect were considered indeterminate, and biopsies that had minimal or no treatment effect were considered positive.. The 5-year rate of actuarial freedom from any failure for the 3-month arm versus the 8-month arm was 72% versus 75% (P = .18). The DFS for patients who had negative and indeterminate biopsies was similar. Two-year post-treatment biopsy status was a strong predictor of 5-year DFS rate (82% and 83% for negative and indeterminate biopsies, respectively, vs 27% for positive biopsies; P < .0001). Multivariate analysis indicated that biopsy status (P < .0001) and Gleason score (P < .0001) were the strongest determinates of biochemical DFS.. Two-year post-RT prostate biopsies were strongly predictive of subsequent DFS. Biopsies with severe treatment effect were considered negative.

Topics: Aged; Aged, 80 and over; Biopsy; Canada; Disease-Free Survival; Flutamide; Goserelin; Humans; Male; Middle Aged; Predictive Value of Tests; Prognosis; Prostatic Neoplasms; Radiotherapy Dosage; Treatment Outcome

We determined whether thalidomide can prolong progression-free survival in men with biochemically recurrent prostate cancer treated with limited androgen deprivation therapy.. A total of 159 patients were enrolled in a double-blind randomized trial to determine if thalidomide can improve the efficacy of a gonadotropin-releasing hormone agonist in hormone responsive patients with an increasing prostate specific antigen after primary definitive therapy for prostate cancer. Patients were randomized to 6 months of gonadotropin-releasing hormone agonist followed by 200 mg per day oral thalidomide or placebo (oral phase A). At the time of prostate specific antigen progression gonadotropin-releasing hormone agonist was restarted for 6 additional months. Patients were then crossed over to the opposite drug and were treated until prostate specific antigen progression (oral phase B). Testosterone and dihydroxytestosterone were likewise monitored throughout the study.. During oral phase A the median time to prostate specific antigen progression was 15 months for the thalidomide group compared to 9.6 months on placebo (p = 0.21). The median time to prostate specific antigen progression during oral phase B for the thalidomide group was 17.1 vs 6.6 months on placebo (p = 0.0002). No differences in time to serum testosterone normalization between the thalidomide and placebo arms were documented during oral phase A and oral phase B. Thalidomide was tolerable although dose reductions occurred in 47% (58 of 124) of patients.. Despite thalidomide having no effect on testosterone normalization, there was a clear effect on prostate specific antigen progression during oral phase B. This is the first study to our knowledge to demonstrate the effects of thalidomide using intermittent hormonal therapy.

Topics: Administration, Oral; Aged; Aged, 80 and over; Androgens; Angiogenesis Inhibitors; Antineoplastic Agents, Hormonal; Cross-Over Studies; Double-Blind Method; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Thalidomide

The identification of surrogate endpoints for prostate cancer-specific survival may shorten the length of clinical trials for prostate cancer. We evaluated distant metastasis and general clinical treatment failure as potential surrogates for prostate cancer-specific survival by use of data from the Radiation Therapy and Oncology Group 92-02 randomized trial.. Patients (n = 1554 randomly assigned and 1521 evaluable for this analysis) with locally advanced prostate cancer had been treated with 4 months of neoadjuvant and concurrent androgen deprivation therapy with external beam radiation therapy and then randomly assigned to no additional therapy (control arm) or 24 additional months of androgen deprivation therapy (experimental arm). Data from landmark analyses at 3 and 5 years for general clinical treatment failure (defined as documented local disease progression, regional or distant metastasis, initiation of androgen deprivation therapy, or a prostate-specific antigen level of 25 ng/mL or higher after radiation therapy) and/or distant metastasis were tested as surrogate endpoints for prostate cancer-specific survival at 10 years by use of Prentice's four criteria. All statistical tests were two-sided.. At 3 years, 1364 patients were alive and contributed data for analysis. Both distant metastasis and general clinical treatment failure at 3 years were consistent with all four of Prentice's criteria for being surrogate endpoints for prostate cancer-specific survival at 10 years. At 5 years, 1178 patients were alive and contributed data for analysis. Although prostate cancer-specific survival was not statistically significantly different between treatment arms at 5 years (P = .08), both endpoints were consistent with Prentice's remaining criteria.. Distant metastasis and general clinical treatment failure at 3 years may be candidate surrogate endpoints for prostate cancer-specific survival at 10 years. These endpoints, however, must be validated in other datasets.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Disease-Free Survival; Dose Fractionation, Radiation; Endpoint Determination; Flutamide; Follow-Up Studies; Goserelin; Humans; Karnofsky Performance Status; Male; Middle Aged; Neoadjuvant Therapy; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Adjuvant; Research Design; Treatment Failure; Treatment Outcome

Radiation Therapy Oncology Group 85-31 was a randomized trial of androgen suppression for life for patients with locally advanced prostate cancer. However, not all patients continued on the protocol-mandated long-term hormonal therapy despite no evidence of recurrence. We correlated duration of adjuvant hormonal therapy and outcomes among patients who prematurely discontinued hormonal therapy.. The protocol mandated pelvic radiotherapy followed by goserelin given indefinitely or until disease progression. There were 189 analyzable patients. Patients were divided in groups based on the tertile of hormonal therapy duration (HTD) as follows: < or = 1 year, more than 1 year and < or = 5 years, and more than 5 years. Overall survival (OS), disease-free survival (DFS), cause-specific mortality, local failure (LF), and distant metastasis (DM) were studied. Kaplan-Meier estimation and Cox proportional hazards regression model were used for OS and DFS, and Fine and Gray's regression model was used for the other outcomes.. The median follow-up for surviving patients is 9.6 years. The median duration of adjuvant hormonal therapy was 2.2 years. The HTD more than 5 years group is significantly associated with an improved survival and DFS and fewer DMs than other HTD groups. After adjustment for age, radical prostatectomy, nodal status, Gleason score, and stage variables, the HTD more than 5 years group remains significantly associated with better OS and DFS than other HTD groups.. In this hypothesis-generating analysis, prolonged HTD of more than 5 years seems significantly associated with improvements in most outcomes. Given these data, decreasing HTD to < or = 5 years may have a detrimental effect on patients with locally advanced prostate cancer. Only a randomized trial will conclusively clarify this issue.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Humans; Male; Middle Aged; Proportional Hazards Models; Prostatic Neoplasms; Survival Rate; Time Factors

Prostate-specific antigen progression (PSA-P) is an indicator of progression in hormone-sensitive (HS) and castration-resistant (CR) prostate cancer (PC). We evaluated different definitions of PSA-P as predictors of overall survival (OS).. A total of 1,078 patients with HSPC who were on hormones (Southwest Oncology Group [SWOG] trial 9346 [S9346]) and 597 patients with CRPC who were treated with chemotherapy (SWOG trial 9916 [S9916]) were eligible for this analysis. PSA-P definitions tested included the following: PSA Working Group, Prostate Cancer Working Group (PCWG 2008), and other definitions. A time-varying approach analyzed associations between PSA-P at any time and OS. A landmark analysis examined the relationship between PSA-P status at 7 months for S9346, or 3 months for S9916, and subsequent OS.. In the time-varying analysis, both working groups definitions were strongly associated with OS (P < .001) in both study settings. In patients enrolled onto S9346, both definitions predicted a 2.4-fold increased risk of death (ROD) and a greater than four-fold increased ROD if PSA-P occurred in the first 7 months. In S9916, they predicted a 40% increase in ROD and a two-fold increase in ROD if PSA-P occurred at 3 months. In landmark analyses of patients on S9346 by using the PCWG 2008 definition of PSA-P, median subsequent OS was 10 months versus 44 months in patients who did or did not have PSA-P by 7 months, respectively; in S9916, data were 11 months versus 18 months for patients who did or did not have PSA-P by 3 months, respectively.. PSA-P, defined as an increase of > or = 25% greater than the nadir and an absolute increase of at least 2 or 5 ng/mL, predicts OS in HSPC and CRPC and may be a suitable end point for phase II studies in these settings.

Topics: Adult; Aged; Aged, 80 and over; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Docetaxel; Estramustine; Goserelin; Humans; Male; Middle Aged; Mitoxantrone; Nitriles; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms; Taxoids; Tosyl Compounds

In this study, we investigated the shrinking effect of concurrent three-dimensional conformal radiotherapy (3D-CRT) and androgen deprivation (AD) on prostate volume, and its possible impact on the dose received by the rectum and bladder during the course of 3D-CRT. The difference between the prostatic volumes determined on pre-treatment planning CT (PL-CT) and post-treatment CT (PT-CT) following a 3D-CRT course was assessed in 52 patients with localised prostate carcinoma. The changes in mean prostate volume when compared with PL-CT and PT-CT-based measurements were assessed. The pre- and post-treatment mean prostate volumes for the whole study population were 49.7 cm(3) and 41.0 cm(3) (p _ 0.02), respectively. The study cohort was divided into two groups depending on the duration of neoadjuvant androgen deprivation (NAD): 23 patients (44.7%) were designated as "short NAD" (< or =3 months; SNAD) and the remaining 29 (55.3%) as "long NAD" (>3 months; LNAD). Patients on SNAD experienced a significantly greater reduction in prostate volume compared with those on LNAD (14.1% vs 5.1%; p _ 0.03). A significant increase in rectum V(40-60) values in PT-CT compared with PL-CT was demonstrated. LNAD patients had significantly higher rectal V(50-70) values at PT-CT compared with the SNAD group. There was a significant decline in V(30)-V(75) bladder values in PT-CT compared with PL-CT in the SNAD group. In conclusion, a higher prostate volume reduction during 3D-CRT was demonstrated when RT planning was performed within 3 months of NAD. However, this reduction and daily organ motion may lead to an unpredictable increase in rectal doses.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nitriles; Prostatic Neoplasms; Radiation Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Conformal; Rectum; Tomography, X-Ray Computed; Tosyl Compounds; Treatment Outcome; Urinary Bladder

To study whether use of neoadjuvant androgen deprivation therapy (N-ADT) combined with whole pelvic radiotherapy (WPRT) for high-risk prostate cancer patients was associated with survival benefit over prostate radiotherapy (PORT) only.. Between 1999 and 2004, 162 high-risk prostate cancer patients were treated with radiotherapy combined with long-term androgen deprivation therapy (L-ADT). Patients were prospectively assigned into two groups: A (N-ADT + WPRT + L-ADT) n = 70 pts, B (PORT + L-ADT) n = 92 pts.. The 5-year actuarial overall survival (OS) rates were 89% for A and 78% for B (P = .13). The 5-year actuarial cause specific survival (CSS) rates were A = 90% and B = 79% (P = .01). Biochemical progression-free survival (bPFS) rates were 52% versus 40% (P = .07), for groups A and B, respectively.. The WPRT combined with N-ADT compared to PORT for high-risk patients resulted in improvement in CSS and bPFS; however no OS benefit was observed.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Goserelin; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoadjuvant Therapy; Neoplasms, Hormone-Dependent; Poland; Prospective Studies; Prostatic Neoplasms; Radiotherapy, Conformal; Risk Factors

Gonadotropin releasing hormone (GnRH) agonists are the cornerstone of metastatic prostate cancer treatment. Cardiovascular effects of GnRH agonists are unclear. In this study, we investigated the short term effects of GnRH agonists on plasma fibrinolytic parameters in patients with metastatic prostate cancer.. Eleven patients (mean age 69.3 +/- 6.5) with metastatic prostate cancer and a clinical indication for GnRH agonist therapy were selected. Plasma plasminogen activator inhibitor (PAI-1) antigen (Ag), tissue plasminogen activator (t-PA) Ag and thrombin-activatable fibrinolysis inhibitor (TAFI) activity levels were measured at baseline and at 4 weeks after the first dose of GnRH agonist, Goserelin Acetate (Zoladex, subcutaneous administration, 10.8 mg).. Serum prostate specific antigen (PSA) levels significantly decreased from 36.6 +/- 19.3 to 1.1 +/- 0.3 ng/ml after Goserelin acetate treatment (P = 0.005). Significant changes occurred in the fibrinolytic parameters. GnRH agonists decreased plasma t-PA Ag levels (16.3 +/- 4.9 vs. 12.2 +/- 2.8 ng/ml, P = 0.047) and increased PAI-1/t-PA molar ratio (4.8 +/- 3.6 vs. 6.6 +/- 3.4, P = 0.16), on the other hand, plasma PAI-1 Ag (59.0 +/- 48.5 vs. 56.4 +/- 30.5 ng/ml, P = 0.8), and TAFI levels (130.6 +/- 9.5 vs. 124.2 +/- 26.5% activity, P = 0.3) did not change significantly.. This study provides evidence that GnRH agonists may inhibit fibrinolytic system by decreasing t-PA levels.

Topics: Aged; Biomarkers; Fibrinolysis; Gonadotropin-Releasing Hormone; Goserelin; Hemostasis; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Tissue Plasminogen Activator

We determined the risk of recurrence in men enrolled on a randomized trial for prostate cancer who were treated with radiation therapy (RT) alone or in conjunction with combined or less than combined androgen suppression therapy (AST).. Between 1995 and 2001, 206 men with localized but unfavorable-risk adenocarcinoma of the prostate were randomly assigned to receive RT or RT and AST, which was defined as 6 months of both a luteinizing hormone-releasing hormone agonist and an antiandrogen. A post-random assignment hypothesis that was generated by multivariable Cox regression analyses was used to evaluate whether the risk of prostate-specific antigen (PSA) recurrence was significantly associated with months of antiandrogen use; regression analysis adjusted for known prognostic factors, comorbidity score, and medications that can elevate liver function tests sufficiently to necessitate discontinuation of the antiandrogen.. After a median follow-up of 8.2 years (interquartile range,7.0 to 9.5 years), 81 men sustained PSA recurrence. An increasing PSA level (P < .001); Gleason score of 8, 9, or 10 (P < .001); and clinical category T2 disease (P = .005) were significantly associated with an increased risk of recurrence. However, recurrence risk was significantly decreased (adjusted hazard ratio, 0.81; 95% CI, 0.72 to 0.92; P = .001) with each additional month of antiandrogen use after analysis was adjusted for these known prognostic factors.. Men with localized but unfavorable-risk prostate cancer who were treated with RT and 6 months of planned combined AST appear to have an increased risk of recurrence when treated with less than as compared with 6 months of the antiandrogen.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors

There were few studies which reported the longitudinal quality of life (QOL) for Japanese men who received endocrine therapy for advanced or metastatic prostate cancer. A pilot randomized trial was conducted to assess QOL and the incidence of hot flash following endocrine therapy using luteinizing hormone-releasing hormone (LH-RH) agonist goserelin acetate 1-month or 3-month depot alone in patients with advanced or metastatic prostate cancer.. A total of 28 patients with advanced or metastatic prostate cancer who received LH-RH analogue goserelin acetate depot alone for 12 months were randomized (1:1) to two different formulations. Fifteen patients received the 1-month depot and thirteen patients received 3-month depot, namely Zoladex 3.6 mg depot and Zoladex LA 10.8 mg depot, respectively. We measured health related QOL using European Organization for Research and Treatment of Cancer (EORTC) and EuroQol (EQ-5D) questionnaire and evaluated the incidence of hot flashes between the two groups for one year after diagnosis. Moreover, we evaluated the incidence of hot flashes between the 1M and 3M depot. A baseline interview was conducted before treatment. Follow-up interviews were conducted in person at scheduled study visits of 3, 6, 9 and 12 months after treatment.. Five (18%) patients dropped out of the study. Thus, we analyzed 23 eligible patients (11 in the 1M arms and 12 in the 3M arms). No significant differences between the two treatment arms were detected in categories of age, average pre- PSA values, Gleason scores and clinical T stage. According to EORTC, each treatment group showed similar QOL scores in all domains before and after treatment. With regard to EQ-5D, the 1M-treatnent arm reported better utility scores than 3M treatment arm, which was no significant statistically. The overall incidence of hot flash was 61% (58% in 1M group and 64% in 3M group).. There were no differences with regard to general and disease specific HRQOL between the both formulations of goserelin acetate. Hot flashes are the major adverse effects of endocrine therapy for Japanese patients with prostate cancer.

Topics: Aged; Antineoplastic Agents, Hormonal; Chemistry, Pharmaceutical; Gonadotropin-Releasing Hormone; Goserelin; Hot Flashes; Humans; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Prostatic Neoplasms; Quality of Life; Surveys and Questionnaires; Time Factors

To determine optimal predictors with which to select the crucial patients enrolled in delayed-combined androgen blockade (CAB) trials, based on risk factors.. From January 2001 to December 2004, 92 prostate cancer patients with T1c, T2 and T3aN0M0 were enrolled in a clinical trial. Medical castration and anti-androgen treatment were used sequentially as delayed-CAB. The prostate specific antigen (PSA) nadir was determined following medical castration only. Anti-androgen treatment was administered if a PSA progression was observed and the subsequent PSA response was evaluated. Time to PSA biochemical failure, induced by medical castration or with anti-androgen treatment, was estimated. Risk factors of PSA failure were evaluated by multivariate analysis.. During luteinizing hormone-releasing hormone (LH-RH) monotherapy, a Kaplan-Meier analysis estimated that the proportion of patients without PSA progression was 64.8% at 5 years. In the multivariate analysis of the prediction of PSA progression with LH-RH monotherapy, a Gleason score over 8, initial PSA >20 ng/ml and PSA nadir >0.2 ng/ml were significant independent risk factors that affected PSA biochemical failure. The PSA progression-free rate in the lower PSA nadir group was significantly lower than that in the other. The 25 patients in the higher PSA nadir group were treated with anti-androgen therapy. Under anti-androgen therapy, the PSA progression-free rate was 62.6% at 5 years. Only PSA nadir >0.2 ng/ml was a significant independent risk factor. The PSA progression-free rate in the lower PSA nadir group was significantly lower than the other.. PSA nadir was the optimal predictive for low stage, non-metastatic population during delayed-CAB.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Monitoring; Gonadotropin-Releasing Hormone; Goserelin; Humans; Kaplan-Meier Estimate; Leuprolide; Male; Middle Aged; Multivariate Analysis; Nitriles; Patient Selection; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; Tosyl Compounds; Treatment Failure

Groups have investigated time to testosterone recovery in patients who have undergone androgen deprivation therapy, usually by measuring androgen every 3 months, with varying results. To our knowledge this represents the largest study using monthly testosterone and dihydroxytestosterone measurement to evaluate the kinetics of androgen recovery following limited androgen deprivation therapy.. Monthly serum androgen levels were analyzed following 2, 6-month cycles of gonadotropin-releasing hormone agonist therapy as part of a randomized, placebo controlled study of the role of thalidomide in delaying time to prostate specific androgen progression.. By the Kaplan-Meier method the median time to testosterone normalization in cycles 1 vs 2 was 15.4 vs 18.3 weeks with similar dihydroxytestosterone recovery times. Neither on-study prostate specific antigen, Gleason score nor thalidomide treatment had a significant impact on time to testosterone normalization. However, in cycle 1 men with low baseline dihydroxytestosterone and those who were more than 67 years old had significantly longer time to T normalization on Cox model analysis. Additionally, in cycle 2 patients with prior local radiation therapy had longer time to testosterone normalization, although this was no longer significant on Cox model analysis. Cox model analysis in cycle 2 showed that low baseline dihydroxytestosterone and testosterone, low testosterone nadir and white race were associated with longer time to testosterone normalization.. Findings of delayed testosterone recovery may be useful for designing and analyzing clinical trials of limited androgen deprivation therapy and for estimating the duration of treatment associated side effects in patients undergoing limited androgen deprivation therapy.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Biopsy, Needle; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Goserelin; Humans; Immunohistochemistry; Leuprolide; Male; Middle Aged; Neoplasm Staging; Probability; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Recovery of Function; Reference Values; Risk Assessment; Testosterone; Thalidomide; Treatment Outcome

Diabetes is associated with lower risk of prostate cancer. Most men with diabetes are obese, and obesity is associated with greater prostate cancer mortality. Whether diabetes influences outcomes after prostate cancer diagnosis is unknown.. We assessed the relationship between prevalent diabetes and mortality using data from Radiation Therapy Oncology Group Protocol 92-02, a large randomized trial of men (N = 1,554) treated with radiation therapy and short-term versus long-term adjuvant goserelin for locally advanced prostate cancer. Regression and proportional hazard models were performed to evaluate relationships between prevalent diabetes and all-cause mortality, prostate cancer mortality, and non-prostate cancer mortality. Covariates included age, race, tumor stage, Gleason score, prostate-specific antigen, weight, and treatment arm.. There were a total of 765 deaths; 210 (27%) were attributed to prostate cancer. In univariate analyses, prevalent diabetes was associated with greater all-cause mortality and non-prostate cancer mortality but not prostate cancer mortality. After controlling for other covariates, prevalent diabetes remained significantly associated with greater all-cause mortality and non-prostate cancer mortality (hazard ratio [HR] = 2.12; 95% CI, 1.69 to 2.66; P < .0001) but not prostate cancer mortality (HR = 0.80; 95% CI, 0.51 to 1.25; P = .34). In contrast, weight was associated with greater prostate cancer mortality (HR = 1.77; 95% CI, 1.22 to 2.55; P = .002) but not all-cause or non-prostate cancer mortality.. Weight but not prevalent diabetes is associated with greater prostate cancer mortality in men receiving combined modality treatment for locally advanced disease. These observations suggest that the association between obesity and greater prostate cancer mortality is mediated by mechanism(s) other than the characteristic metabolic alterations of diabetes.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents, Hormonal; Diabetes Mellitus, Type 2; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Radiotherapy

The aim of this study was to determine the effects of anti-androgens on left ventricular (LV) function and levels of N-terminal proB-type natriuretic peptide (NT-proBNP), a sensitive cardiac risk marker, in men with prostate cancer as these are widely used drugs in this condition, and evidence suggests that endogenous androgens are cardioprotective in men.. Forty-three men (mean age 70.7 +/- 6.2 years) with prostate cancer were randomized to goserelin (an LH-releasing hormone analogue) or bicalutamide (an androgen-receptor blocker) for 6 months; 20 men with a history of prostate cancer on no treatment were studied in parallel.. Mean changes in testosterone and oestradiol, respectively, from baseline to 6 months were -88% and -46% with goserelin, +50% and +44% with bicalutamide, and -1% and -9% for the 'no-treatment' group. Bicalutamide significantly increased NT-proBNP from baseline to 3 and 6 months (median value at baseline, 3 and 6 months: 55, 101 and 118 ng/l, respectively). Goserelin caused a significant increase from baseline to 3 months but not to 6 months (median value at baseline, 3 and 6 months: 66, 87 and 72 ng/l, respectively). No significant changes occurred in the 'no-treatment' cohort (median value at baseline 3 and 6 months: 60, 53 and 60 ng/l, respectively). No significant changes in LV function, blood pressure (BP), body mass index or waist-hip ratio occurred to account for the changes in NT-proBNP.. Androgen receptor blockade and, to a lesser extent, androgen suppression cause an increase in NT-pro-BNP in men with prostate cancer. The significance is not clear but could imply an adverse effect on cardiovascular risk following hormonal manipulation.

Topics: Aged; Androgen Antagonists; Anilides; Estradiol; Goserelin; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Nitriles; Peptide Fragments; Prostatic Neoplasms; Testosterone; Tosyl Compounds

Late gastrointestinal (GI) and genitourinary (GU) morbidity from external beam irradiation used to treat adenocarcinoma of the prostate continue to be a concern of physicians and patients alike. In addition, for locally advanced/high-risk cancer, the appropriate use of hormonal manipulation in addition to radiation therapy (RT) may increase toxicity. We analyzed three large Radiation Therapy Oncology Group (RTOG) studies (85-31, 86-10, and 92-02) to try to address these issues.. A total of 2,922 patients were accrued with a median follow-up of 10.3 years for surviving patients. The RTOG scoring scheme was used to assess GI, GU, and other toxicities. Toxicity reported was Grade 3 or higher late toxicity. Patient toxicity level was assessed by study and by treatment type combining RT only vs. RT + short-course hormone therapy (STH) vs. RT + long-term hormone therapy (LTH).. Multivariate analysis reveals that age >70 was statistically significantly associated with a decrease in late any Grade 3+ toxicity (hazard ratio [HR] = 0.78, p = 0.0476) adjusted for treatment type. Comparing treatment type, patients treated with RT+STH had a statistically significant lower probability of Grade 3+ GI, GU, and other toxicity compared with RT alone (p = .00006; p = 0.0037; p = 0.0127, respectively). Patients treated with RT+LTH had a statistically significant lower probability of Grade 3+ GU toxicity compared with RT alone (p = 0.023).. These data show that external beam radiation therapy remains a safe option for locally advanced/high-risk prostate cancer, and the use of hormonal manipulation does appear to be protective for GU and GI toxicity depending upon length of treatment.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Combined Modality Therapy; Flutamide; Follow-Up Studies; Gastrointestinal Tract; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiation Injuries; Urogenital System

Testosterone administration can lead to increased antipyrine clearance in humans. Medical or surgical castration is a standard treatment of progressive prostate carcinoma, but the effect of the subsequent fall of testosterone concentrations upon drug metabolism has not been reported.. Eleven men with a biopsy-proven diagnosis of progressive prostate cancer were enrolled after providing informed consent. CYP3A4 activity was determined using the erythromycin breath test (EBT) in each patient prior to their beginning with an LHRH-agonist (leuprolide or goserelin). No patients had elected to undergo orchiectomy during the period of subject accrual. Each subject underwent a second EBT 2 months after beginning LHRH suppression. Blood samples were collected at these time points to determine changes in testosterone and leutinizing hormone.. All subjects had a predictable drop in serum testosterone concentrations over the 8-week course of the study, but concentrations in three did not fall below castrate levels (<50 ng/dl). There was no statistically significant change in CYP3A4 activity using the EBT method (p = 0.88). The extent and direction of changes in CYP3A4 activity was highly variable, with three subjects experiencing an increase in activity, and five demonstrating a decrease in activity.. There is no clinically significant change in CYP3A4 activity after medical castration. No changes in the clearance of docetaxel or other CYP3A4 substrates are likely during and after medical castration. Although similar findings are expected after orchiectomy, we were not able to test this presumption because of patient preference for medical castration.

Topics: Aged; Antineoplastic Agents, Hormonal; Breath Tests; Cytochrome P-450 CYP3A; Erythromycin; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Testosterone

Radiation Therapy Oncology Group (RTOG) 8610 was the first phase III randomized trial to evaluate neoadjuvant androgen deprivation therapy (ADT) in combination with external-beam radiotherapy (EBRT) in men with locally advanced prostate cancer. This report summarizes long-term follow-up results.. Between 1987 and 1991, 456 assessable patients (median age, 70 years) were enrolled. Eligible patients had bulky (5 x 5 cm) tumors (T2-4) with or without pelvic lymph node involvement according to the 1988 American Joint Committee on Cancer TNM staging system. Patients received combined ADT that consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg tid for 2 months before and concurrent with EBRT, or they received EBRT alone. Study end points included overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), disease-free survival (DFS), and biochemical failure (BF).. Ten-year OS estimates (43% v 34%) and median survival times (8.7 v 7.3 years) favored ADT and EBRT, respectively; however, these differences did not reach statistical significance (P = .12). There was a statistically significant improvement in 10-year DSM (23% v 36%; P = .01), DM (35% v 47%; P = .006), DFS (11% v 3%; P < .0001), and BF (65% v 80%; P < .0001) with the addition of ADT, but no differences were observed in the risk of fatal cardiac events.. The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Combined Modality Therapy; Disease-Free Survival; Flutamide; Follow-Up Studies; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Prostatic Neoplasms; Survival Rate

Gonadotropin-releasing hormone agonists (GnRHa) are associated with greater risk of coronary heart disease and myocardial infarction in men with prostate cancer, but little is known about their potential effects on cardiovascular mortality. We assessed the relationship between duration of GnRHa therapy and cardiovascular mortality in a large randomized trial of men treated with short-term versus longer-term adjuvant goserelin and radiation therapy (RT) for locally advanced prostate cancer.. From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-4, prostate-specific antigen [PSA] <150 ng/ml) received RT and 4 mo of goserelin and then were randomized to no additional therapy (arm 1) or 24 mo adjuvant goserelin (arm 2) in a phase 3 trial (Radiation Therapy Oncology Group [RTOG] 92-02). Cox regression analyses were performed to evaluate the relationship between treatment arm and cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes (DM), race, PSA, Gleason score, and stage.. After median follow-up of 8.1 yr, 185 cardiovascular-related deaths had occurred. No increase in cardiovascular mortality occurred for men receiving a longer duration of goserelin. At 5 yr, cardiovascular mortality for men receiving longer-term adjuvant goserelin was 5.9% versus 4.8% with short-term goserelin (Gray's p=0.16). In multivariate analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR]=1.09; 95% confidence interval [CI], 0.81-1.47; p=0.58; when censoring at time of salvage goserelin, HR=1.02, 95%CI, 0.73-1.43; p=0.9). Traditional cardiac risk factors, including age, prevalent CVD, and DM, were significantly associated with greater cardiovascular mortality.. Longer duration of adjuvant GnRHa therapy does not appear to increase cardiovascular mortality in men with locally advanced prostate cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Flutamide; Goserelin; Humans; Male; Middle Aged; Multivariate Analysis; Prostatic Neoplasms; Time Factors

Southwest Oncology Group (SWOG) study 9921 is a randomized, phase III, intergroup study to define the role of adjuvant chemotherapy in patients with high-risk prostate cancer.. We allocated 983 patients with prostate cancer with high-risk features to receive 2 years of androgen-deprivation therapy (ADT) with or without six cycles of mitoxantrone (12 mg/m(2)) after prostatectomy.. In January 2007, SWOG 9921 was closed to further accrual after three cases of acute myelogenous leukemia (AML) were reported of a total of 487 patients in the mitoxantrone treatment arm. The key cytogenetic features of these cases included inv(16) in the first case, t(15;17) in the second, and del(5) in the third case. Time from the start of mitoxantrone to the detection of AML was 13, 48, and 72 months, respectively. Before SWOG 9921, there were no cases of mitoxantrone-induced AML reported in patients treated for prostate cancer.. The emergence of this possible pattern of secondary malignancy emphasizes the importance of randomized controlled trials in defining safety and efficacy of new approaches for patients in the adjuvant setting.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anilides; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Fatal Outcome; Goserelin; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mitoxantrone; Nitriles; Prednisone; Prostatectomy; Prostatic Neoplasms; Risk Assessment; Risk Factors; Southwestern United States; Survival Analysis; Tosyl Compounds

This study used tumour specimens from a clinical trial on intermittent androgen suppression (IAS) to study the effects of castration on tissue morphology, cell proliferation, apoptosis, and the expression of androgen receptor (AR).. A total of 113 representative needle biopsy specimens were available from 29 patients for evaluation of the Gleason score as well as Ki-67, cleaved caspase-3, and AR immunostaining.. At 6 mo from the beginning of the first androgen withdrawal, cell proliferation activity was significantly (p = 0.002) reduced, whereas no effect on apoptosis was found. A nonsignificant trend to an increase in Gleason score after castration was found. Subsequent cycles of withdrawals had no significant effect on any of the measured parameters. The Gleason score, proliferation activity, and apoptosis rate showed only heterogeneous, nonsignificant changes after the first progression. Strong nuclear AR staining was evident in all cancer specimens.. The findings suggest that the long-term (months) effect of androgen withdrawal on tumour growth is due to the inhibition of proliferation. Because the tumours seem to become resistant to castration at the first cycle of treatment withheld, it is possible that IAS does not postpone the emergence of ablation-resistant tumours. There was no consistent sign of increased proliferation or Gleason score during the treatment, suggesting that the biologic aggressiveness of a particular tumour is defined already at an early stage of disease. The constant nuclear expression of AR in cancer cells indicates that the AR signalling remains active despite of the androgen withdrawal.

Topics: Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Apoptosis; Biomarkers, Tumor; Biopsy, Needle; Caspase 3; Cell Proliferation; Disease Progression; Dose-Response Relationship, Drug; Follow-Up Studies; Goserelin; Humans; Immunohistochemistry; Ki-67 Antigen; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Outcome

To compare combination therapy with bicalutamide 80 mg and a luteinizing hormone-releasing hormone agonist (LHRH-A) versus LHRH-A alone in Japanese men with untreated advanced prostate cancer. A total of 205 patients with stage C/D prostate cancer were randomized to either LHRH-A+once-daily oral bicalutamide 80 mg or placebo. Primary study variables have been reported previously. Secondary variables included: time to achieve prostate-specific antigen < or = 4 ng/ml, time-to-treatment failure (TTTF), time-to-disease progression (TTP), overall survival (OS), adverse events and adverse drug reactions. Following combination therapy with bicalutamide 80 mg, there were significant (P<0.001) advantages over LHRH-A alone in terms of TTTF and TTP, but the difference in the interim OS was not statistically significant. First-line combination therapy with bicalutamide 80 mg in Japanese patients with advanced prostate cancer offers significant benefits over LHRH-A alone, with respect to TTTF and TTP. Follow-up for OS continues.

Topics: Aged; Anilides; Double-Blind Method; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

Inherited genotypes may explain the inferior outcomes of African American (AA) men with prostate cancer. To understand how variation in CYP3A4 correlated with outcomes, a retrospective examination of the CYP3A4 *1B genotype was performed on men treated with Radiation Therapy Oncology Group (RTOG) 92-02.. From 1,514 cases, we evaluated 56 (28.4%) of 197 AA and 54 (4.3%) of 1,274 European American (EA) patients. All patients received goserelin and flutamide for 2 months before and during RT (STAD-RT) +/- 24 months of goserelin (long-term androgen deprivation plus radiation [LTAD-RT]). Events studied included overall survival and biochemical progression using American Society for Therapeutic Radiology and Oncology consensus guidelines.. There were no differences in outcome in patients in with or without CYP3A4 data. There was an association between race and CYP3A4 polymorphisms with 75% of EAs having the Wild Type compared to only 25% of AA men (p <0.0001). There was no association between CYP3A4 classification or race and survival or progression.. The samples analyzed support previously reported observations about the distribution of CYP3A4 *1B genotype by race, but race was not associated with poorer outcome. However, patient numbers were limited, and selection bias cannot be completely ruled out.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Black People; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Disease Progression; Flutamide; Genotype; Goserelin; Humans; Male; Neoplasm Proteins; Practice Guidelines as Topic; Prostate-Specific Antigen; Prostatic Neoplasms; Regression Analysis; Survival; White People

We examined overall and disease-specific survival outcomes both from the time of initial treatment and from the start of salvage hormone therapy (HT), by the extent of disease progression at the time salvage HT was started in patients treated on RTOG Protocol 86-10.. [corrected] With a median follow-up of 9.0 years, 247 patients (54%) had received subsequent salvage HT. The overall survival (OVS) and disease-specific survival (DSS) were compared by the extent of disease progression at the time salvage HT was started.. For those patients with distant metastases (DM) present at the start of salvage HT, the OVS and DSS were significantly reduced when compared to [corrected] those with DM absent at the time salvage HT was started (OVS at 8 years, 31% vs. 58%; DSS at 8 years, 38% vs. 65%). A statistically significant increase in DSS was observed among the 143 patients with DM absent when patients with prostate-specific antigen (PSA) less than 20 were compared with those with PSA greater than 20 at the time salvage HT was started.. [corrected] The DSS and the OVS of the relapsed patient are decreased in those with more extensive disease at the time of salvage HT. However, because this protocol could not evaluate the effect of posttreatment PSA velocity on outcomes, which is likely a better predictor of long-term success with salvage HT, these results cannot be taken to demonstrate that early salvage HT in patients with long posttreatment PSA doubling times is necessary for longer survival.

Topics: Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease-Free Survival; Flutamide; Goserelin; Humans; Male; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Salvage Therapy; Treatment Failure

Tumour features were evaluated during intermittent androgen suppression (IAS), and their prognostic impact on the first off-treatment time was analysed.. Twenty patients with advanced prostate cancer underwent three consecutive prostate biopsies during the first cycle, namely at the beginning of androgen deprivation, 8 months after continuous therapy and at the time of prostate-specific antigen (PSA) progression above 20 ng/ml. Biopsy specimens were immunohistochemically processed and analysed for the apoptotic index (AI), Ki-67, p53 and Bcl-2 to investigate eventual changes over time. Correlations and regression analysis were performed to assess the prognostic significance of clinical and pathological parameters in predicting the first off-treatment time.. In contrast to the AI, p53 and Bcl-2, Ki-67 was the only marker that significantly changed over time (P=0.008). The first off-treatment time correlated significantly with pretreatment PSA (r=-0.594; P<0.01), testosterone recovery time (r=0.590; P=0.013) and biopsy grade (r=-0.738; P<0.01); only the latter gaining an independent factor in the multivariate analysis (P=0.022).. During IAS, Ki-67 was the only molecular marker that consistently changed over time. However, it did not correlate with off-treatment time that was predicted independently by the initial biopsy grade only. First off-treatment time was best predicted by clinical parameters and molecular markers from needle biopsies did not further contribute to a better patient selection.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy; Carcinoma; Cell Proliferation; Gene Expression Regulation, Neoplastic; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Nitriles; Prognosis; Prostatic Neoplasms; Testosterone; Tosyl Compounds; Withholding Treatment

To evaluate the clinicopathological outcomes of 8 months of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy for high-risk prostate cancer.. A multi-institutional prospective trial was performed between July 2000 and May 2003 involving high-risk prostate cancer patients without metastasis, including 21 who received 8 months of NHT before radical prostatectomy. High-risk group was defined as clinical stage > or =T2c and/or prostate-specific antigen (PSA) >20 ng/ml and/or Gleason score > or =8. PSA values were considered elevated (biochemical failure) if values of 0.1 ng/ml or greater were obtained.. Median of initial PSA levels before prostate biopsy was 27.6 ng/ml (8.5-80.7 ng/ml), and median of pre-operative PSA levels after NHT was 0.28 ng/ml (0.02-4.2 ng/ml). There were 5 patients (23.8%) with lower limit of PSA detection (less than 0.02 ng/ml) in 8 months after NHT. The clinical T stage was T1c in 9 patients (42.9%), T2a-b in 8 patients (38.1%), T2c in 3 patients (14.3%), and T3a in 1 patient (4.8%). The median follow-up was 25 months (range 4 to 37). There were 2 patients (9.5%) in pT0, 5 patients (23.8%) with positive surgical margin, 5 patients (23.8%) with extracapsular extension (ECE) and 3 patients (14.3%) with seminal vesicle involvement (SVI). Biochemical failure was occurred in 9 of 21 (42.9%) including of one pT0. Range of time to postoperative biochemical failure was 2 to 25 months (median 6 months) and most of biochemical failure was found within 12 months after surgery. Biochemical failure rate was significantly higher in patient with positive SVI (p = 0.0308) and higher in patients with pre-operative PSA levels of more than 0.1 ng/ml (p = 0.0836), positive ECE (p = 0.0545) and positive surgical margin (p = 0.0545).. Biochemical failure was frequent after this combined treatment, even in a pT0 case. Long-term follow-up of patients is needed to assess the impact of this therapy on mortality.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Chemotherapy, Adjuvant; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nitriles; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Risk; Time Factors; Tosyl Compounds; Treatment Failure

To update the effect of immediate androgen suppression in conjunction with standard external-beam irradiation versus radiation alone on a group of histologically lymph node-positive patients with adenocarcinoma of the prostate.. A national prospective randomized trial (Radiation Therapy Oncology Group 85-31) of standard external-beam irradiation plus immediate androgen suppression versus external-beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate. One hundred seventy-three patients in this trial had histologically involved lymph nodes. Ninety-eight patients received radiation plus immediate androgen suppression (luteinizing hormone-releasing hormone [LHRH] agonist), whereas 75 patients received radiation alone with hormonal manipulation instituted at the time of relapse.. With a median follow-up of 6.5 years for all patients and 9.5 years for living patients, estimated progression-free survival with prostate-specific antigen (PSA) level less than 1.5 ng/mL at 5 and 9 years was 54% and 33%, respectively, for patients who received immediate LHRH agonist versus 10% [corrected] and 4% for patients who received radiation alone with hormonal manipulation instituted at time of relapse (P < .0001). Multivariate analysis revealed radiation therapy and immediate hormonal manipulation as having a statistically significant impact on all end points analyzed: absolute survival, disease-specific failure, metastatic failure, and biochemical control with PSA less than 4 ng/mL and less than 1.5 ng/mL.. Pending the results of randomized trials, patients with adenocarcinoma of the prostate who have pathologically involved pelvic lymph nodes (pathologic node-positive or clinical stage D1) should be considered for external-beam irradiation plus immediate hormonal manipulation rather than radiation alone with hormone manipulation at the time of relapse.

Topics: Adenocarcinoma; Adult; Aged; Combined Modality Therapy; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Prostatic Neoplasms

A randomized controlled trial has started in Japan to evaluate radiotherapy and endocrine therapy for prostate-specific antigen (PSA) failure after radical prostatectomy. Patients who have PSA failure after radical prostatectomy for localized prostate cancer (T1-2N0M0) are randomized into treatment groups of either radiotherapy +/- endocrine therapy or endocrine therapy alone. The Urologic Oncology Study Group (UOSG) in the Japan Clinical Oncology Group (JCOG) composed of 36 specialized institutions will recruit 200 patients. The primary end-point is time to treatment failure (TTF) of bicalutamide, and secondary end-points are TTF of protocol treatment, progression-free survival, overall survival, adverse events and quality of life (QOL). The Clinical Trial Review Committee of the JCOG approved the protocol on April 13, 2004, and the study was activated on May 17, 2004.

Topics: Adult; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Endpoint Determination; Goserelin; Humans; Male; Middle Aged; Nitriles; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Quality of Life; Radiotherapy Dosage; Survival Rate; Tosyl Compounds

To determine whether needle size influences a patient's perception of pain, 50 patients requiring hormonal manipulation for prostate cancer were blindfolded and randomised to receive two goserelin ('Zoladex') or two leuprorelin ('Prostap') injections, using 16- or 23-gauge needles, respectively. Median visual analogue scale pain scores for the first injections of goserelin and leuprorelin were below the level of clinical significance and were not statistically different. Mean administration time for goserelin was significantly shorter than for leuprorelin. In conclusion, there was no statistically significant difference in pain experienced on injection of goserelin and leuprorelin when patients were unaware of needle size.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Goserelin; Humans; Leuprolide; Male; Middle Aged; Needles; Pain; Pain Measurement; Patient Satisfaction; Prostatic Neoplasms; Single-Blind Method

To evaluate the efficacy of bicalutamide vs cyproterone acetate in preventing PSA flare (as a surrogate for tumour flare) for patients requiring luteinizing hormone-releasing hormone (LHRH) analogue therapy for prostate cancer.. In this pilot study, 40 men were randomized 1 : 1 to bicalutamide 50 mg o.d. or cyproterone acetate 100 mg t.i.d. 5 days prior to goserelin acetate and continued for 21 days thereafter. PSA, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone were obtained before treatment and on days 6, 8, 10, 16, 21 and 28. Primary end point was PSA. Hormone profile and clinical features including urinary symptoms and bone pain were secondary end points.. Both groups were equally matched apart from serum creatinine and ALP. The speed and magnitude of the percentage change in median PSA from baseline was increased for the CPA group but there was no statistically significant difference in the two groups. Although those receiving bicalutamide all showed a testosterone peak, this remained within the normal range. No difference in the frequency of drug-specific adverse events was found. None of the patients died or developed cord compression during the study period.. Bicalutamide is able to suppress the initial PSA surge as effectively as cyproterone acetate albeit slightly delayed. A statement whether bicalutamide is equally good at preventing clinical flare cannot be made and should be assessed in an appropriately powered study.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Cyproterone Acetate; Goserelin; Humans; Injections, Subcutaneous; Male; Nitriles; Pain; Prostatic Neoplasms; Tosyl Compounds

Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT).. Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression.. Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm.. In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival. The improvement in survival appeared preferentially in patients with a Gleason score of 7-10.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Goserelin; Humans; Male; Multivariate Analysis; Prostatectomy; Prostatic Neoplasms; Survival Rate

Patients with prostate cancer are treated with neoadjuvant, adjuvant and intermittent therapy with gonadotropin-releasing hormone agonists (GnRH-A). While these are largely successful in decreasing testosterone (T) and dihydroxytestosterone (DHT) to castrate levels, discontinuation of such therapy often results in continued suppression of androgens for variable periods of time. We present the largest published series of patients evaluating the timing of T and DHT increase after cessation of GnRH therapy.. Serial T and DHT measurements were prospectively obtained every 3 months while on GnRH-A then monthly upon discontinuation of GnRH-A. Analysis of time from the second 3-month GnRH-A administration to T and DHT increase was undertaken.. A total of 80 evaluable patients had a median time to T 50 ng/dl or greater of 12.9 weeks and a median time to T normalization (212 ng/dl or greater) of 16.6 weeks. Low baseline T was associated with a prolonged time to T 212 ng/dl or greater (p = 0.0086) and a similar trend was seen in patients older than 66 years (p = 0.08). There were 62 evaluable patients with a median of 14.9 weeks to DHT 150 pg/ml or greater. There was no association with Gleason score at diagnosis, on study prostate specific antigen, type of prior definitive therapy, or any prior hormonal therapy and time to increase in circulating androgens.. After 6 months of GnRH-A therapy in these patients, DHT and T levels did not return to normal for a median of 14.9 and 16.6 weeks, respectively.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Testosterone; Time Factors

Prostatectomy or radiation for localized prostate cancer (PC) can fail in up to 15% to 30% of patients. The purpose of this study was to determine feasibility, tolerability, and outcome of docetaxel followed by hormone therapy in men experiencing an increasing prostate-specific antigen (PSA) after their primary local treatments for PC.. Men with increasing serum PSA after prostatectomy or/and radiation were eligible. Serum PSA had to be > or = 4 ng/mL and serum testosterone had to be in the noncastrate range. Treatment included docetaxel 70 mg/m2 every 3 weeks for up to six cycles, followed by total androgen suppression (luteinizing hormone-releasing hormone agonist plus bicalutamide) and peripheral androgen blockade (finasteride plus bicalutamide) for 12 to 20 months.. Thirty-nine men were enrolled; 32 had PSA-only failure, seven also had clinical metastasis. Baseline median PSA was 13.7 ng/mL. Serum PSA decreased > or = 50% in 17 of 35 patients (48.5%) and > or = 75% in seven of 35 patients (20%) with docetaxel. The PSA decreased to a median of 0.1 ng/mL with subsequent hormone therapy. In 28 of 33 patients the PSA increased (median, 0.41 ng/mL) at a median follow-up of 2.3 months after treatment. In contrast, in five of 33 men the PSA remains at 0.1 ng/mL at a median of 18.9 months after therapy; three of these five men had soft tissue metastasis at entry but remain in complete remission. The most common grade 3 to 4 toxicity was neutropenia (61.5%).. Docetaxel followed by hormone therapy of limited duration may provide disease control in subgroups of men experiencing failure after local treatments for PC.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Docetaxel; Goserelin; Humans; Infusions, Intravenous; Injections, Intramuscular; Injections, Subcutaneous; Leuprolide; Male; Middle Aged; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Taxoids; Treatment Outcome

To examine, in a prospective study, the influence that temporary reversible medical castration for localized prostate cancer has on cognition, by assessing whether temporary 3-5 month treatment with a luteinizing-hormone releasing hormone (LHRH) agonist before radical radiotherapy had a short- or long-term affect on cognitive function.. Thirty-two patients with localized prostate cancer had cognitive assessments at baseline (T1) before the start of drug treatment, at 3 months (T2) or on completing drug treatment but before radiotherapy, and 9 months later (T3). Eighteen men with no prostate cancer (controls subjects) completed the cognitive tests at the same times. In addition, psychological functioning and quality of life were assessed at the same times, together with serum free and bound testosterone, beta-oestradiol and sex hormone-binding globulin levels.. There was a significant cognitive decline (on at least one cognitive task) at T2 in 15 (47%) patients vs three (17%) of controls (odds ratio 4.412, P = 0.033). Most patients (nine of 15) who had a change in performance declined on tasks of spatial memory and ability. At T3 there was significant cognitive decline in 11 (34%) patients and five (28%) control subjects (odds ratio 1.37, P = 0.631).. This pilot study suggests that short-term LHRH therapy for early-stage prostate cancer has modest short-term consequences on men's cognitive functioning; a larger prospective study is warranted.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cognition Disorders; Cyproterone Acetate; Goserelin; Humans; Intelligence; Male; Memory Disorders; Middle Aged; Neoadjuvant Therapy; Pilot Projects; Prostatic Neoplasms; Quality of Life; Speech Disorders; Surveys and Questionnaires

Androgen deprivation is an established treatment regimen for disseminated prostate cancer; however, its role in patients with localised cancer is less clear. We did a large randomised controlled trial to determine whether 3 months or 6 months of androgen deprivation given before and during radiotherapy improves outcomes for patients with locally advanced prostate cancer.. 818 men with locally advanced prostate cancer were randomly assigned to: no androgen deprivation (ie, radiotherapy alone: 66 Gy in 33 fractions of 2 Gy per day over 6.5-7.0 weeks to the prostate and seminal vesicles); 3 months' androgen deprivation with 3.6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day starting 2 months before radiotherapy (same regimen as control group); or 6 months' androgen deprivation, with the same regimen, starting 5 months before radiotherapy (same regimen as control group). Primary endpoints were time to local failure and prostate-cancer-specific survival; secondary endpoints were distant failure, disease-free survival, and freedom from salvage treatment. Analyses were done by intention to treat.. 802 (98%) patients were eligible for analysis. Median follow-up was 5.9 years (range 0.1-8.5). Compared with patients assigned no androgen deprivation, those assigned 3 months' treatment had significantly improved local failure (hazard ratio [HR] 0.56 [95% CI 0.39-0.79], p=0.001), biochemical failure-free survival (0.70 [0.56-0.88], p=0.002), disease-free survival (0.65 [0.52-0.80], p=0.0001), and freedom from salvage treatment (0.73 [0.56-0.96], p=0.025). 6 months' androgen deprivation significantly improved local failure (0.42 [0.28-0.62], p<0.0001), biochemical failure-free survival (0.58 [0.46-0.74], p<0.0001), disease-free survival (0.56 [0.45-0.69], p<0.0001), freedom from salvage treatment (0.53 [0.40-0.71], p<0.0001), distant failure (0.67 [0.45-0.99], p=0.046) and prostate-cancer-specific survival (0.56 [0.32-0.98], p=0.04) compared with no androgen deprivation.. 6 months' androgen deprivation given before and during radiotherapy improves the outlook of patients with locally advanced prostate cancer. Further follow-up is needed to estimate precisely the size of survival benefits. Increased radiation doses and additional periods of androgen deprivation might lead to further benefit.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Disease-Free Survival; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Prostatic Neoplasms

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Drug Administration Schedule; Goserelin; Humans; Injections, Intramuscular; Injections, Subcutaneous; Leuprolide; Male; Prospective Studies; Prostatic Neoplasms; Radiotherapy, Conformal; Treatment Outcome

The aim of this study was to compare the speed of administration (preparation and delivery) and nurses' perceived ease of use and relative safety of two injection systems used to administer luteinising hormone-releasing hormone agonists: a depot system used to administer goserelin acetate ('Zoladex', AstraZeneca) and a vial system used to administer leuprorelin acetate ('Prostap', Wyeth). This was a randomised, crossover study with 82 volunteer nurses (50 pre-registration and 32 post-registration). All nurses were timed in the administration of both systems and all were required to assess the two systems by completing a questionnaire. Results indicate that both pre- and post-registration nurses administered the depot system in less time than the vial system. Overall mean times for administration of the depot system and the vial system were 1.70 and 3.34min, respectively. In questionnaire responses, significantly more nurses thought that the depot system had 'good safety precautions' compared with the vial system (85% versus 40%; P<0.001) and significantly more nurses also expressed a preference for the depot system (58% versus 42%; P=0.036). In conclusion, this study demonstrates that nurses prefer the one-step depot system used to administer goserelin acetate over the vial system used to administer leuprorelin acetate.

Topics: Antineoplastic Agents, Hormonal; Attitude of Health Personnel; Cross-Over Studies; Delayed-Action Preparations; Drug Delivery Systems; England; Goserelin; Humans; Injections; Leuprolide; Male; Prostatic Neoplasms; Time Factors

To evaluate bicalutamide (Casodex) 80 mg as a component of maximum androgen blockade (MAB) in Japanese patients with previously untreated advanced prostate cancer.. 205 patients with previously untreated stage C/D prostate cancer were randomized (1:1) to receive once-daily bicalutamide 80 mg or placebo, each combined with a luteinizing hormone-releasing hormone (LHRH) agonist. Primary study variables were the 12 week prostate-specific antigen (PSA) normalization (i.e. PSA level

Topics: Aged; Anilides; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Disease-Free Survival; Double-Blind Method; Goserelin; Humans; Japan; Leuprolide; Lymphatic Metastasis; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Tosyl Compounds; Treatment Outcome

To investigate the effects of different management strategies for non-localized prostate cancer on men's quality of life and cognitive functioning.. Men with prostate cancer were randomly assigned to one of four treatment arms: leuprorelin, goserelin, cyproterone acetate (CPA), or close clinical monitoring. In a repeated-measures design, men were assessed before treatment (baseline) and after 6 and 12 months of treatment. A community comparison group of men of the same age with no prostate cancer participated for the same length of time. The men were recruited from public and private urology departments from university teaching hospitals. All those with prostate cancer who were eligible for hormonal therapy had no symptoms requiring immediate therapy. In all, 82 patients were randomized and 62 completed the 1-year study, and of the 20 community participants, 15 completed the study. The main outcome measures were obtained from questionnaires on emotional distress, existential satisfaction, physical function and symptoms, social and role function, subjective cognitive function, and sexual function, combined with standard neuropsychological tests of memory, attention, and executive functions.. Sexual dysfunction increased for patients on androgen-suppressing therapies, and emotional distress increased in those assigned to CPA or close clinical monitoring. Compared with before treatment there was evidence of an adverse effect of leuprorelin, goserelin, and CPA on cognitive function.. In deciding the timing of androgen suppression therapy for prostate cancer, consideration should be given to potential adverse effects on quality of life and cognitive function.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cognition Disorders; Cyproterone Acetate; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Quality of Life; Sexual Dysfunction, Physiological; Stress, Psychological

The timing of endocrine treatment for prostate cancer remains controversial. The issue is addressed in protocol 30846 of the European Organisation for Research and Treatment of Cancer for patients with lymph node positive cancer without local treatment of the primary tumor.. A total of 302 patients with metastatic regional lymph nodes who had not received local treatment for the primary tumor were included in the trial, of whom 234 were randomized to immediate vs delayed endocrine treatment. Endocrine treatment consisted of an luteinizing hormone-releasing hormone agonist and 1 month of antiandrogen treatment or surgical castration. The main end point of the trial was overall survival. Analysis followed the intent to treat principle.. At a median followup of 9.6 years (8.7 in the randomized sample) 190 patients (62.9%) had died, including 76% of prostate cancer. In the randomized sample the HR for survival on delayed vs immediate treatment was 1.23 (95% CI 0.88 to 1.71), indicating a 23% nonsignificant trend in favor of early treatment. However, the wide CI showed that results remained compatible with true effects, ranging from a 12% benefit in favor of delayed treatment to a 71% detriment for the same treatment approach.. While this study suggests an advantage for early treatment, it is under powered to show equivalence or superiority for the early or delayed approach. When dealing with individual patients, the potential survival advantage on early treatment must be balanced against potential advantages in quality of life on delayed treatment.

Topics: Adult; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cyproterone Acetate; Drug Therapy, Combination; Follow-Up Studies; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Prostatic Neoplasms; Survival Rate; Time Factors

Survival benefit in the management of high-grade clinically localized prostate cancer has been shown for 70 Gy radiation therapy combined with 3 years of androgen suppression therapy (AST), but long-term AST is associated with many adverse events.. To assess the survival benefit of 3-dimensional conformal radiation therapy (3D-CRT) alone or in combination with 6 months of AST in patients with clinically localized prostate cancer.. A prospective randomized controlled trial of 206 patients with clinically localized prostate cancer who were randomized to receive 70 Gy 3D-CRT alone (n = 104) or in combination with 6 months of AST (n = 102) from December 1, 1995, to April 15, 2001. Eligible patients included those with a prostate-specific antigen (PSA) of at least 10 ng/mL, a Gleason score of at least 7, or radiographic evidence of extraprostatic disease.. Time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits) and overall survival.. After a median follow-up of 4.52 years, patients randomized to receive 3D-CRT plus AST had a significantly higher survival (P =.04), lower prostate cancer-specific mortality (P =.02), and higher survival free of salvage AST (P =.002). Kaplan-Meier estimates of 5-year survival rates were 88% (95% confidence interval [CI], 80%-95%) in the 3D-CRT plus AST group vs 78% (95% CI, 68%-88%) in the 3D-CRT group. Rates of survival free of salvage AST at 5 years were 82% (95% CI, 73%-90%) in the 3D-CRT plus AST group vs 57% (95% CI, 46%-69%) in the 3D-CRT group.. The addition of 6 months of AST to 70 Gy 3D-CRT confers an overall survival benefit for patients with clinically localized prostate cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Goserelin; Humans; Leuprolide; Male; Middle Aged; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Conformal; Survival Analysis

To evaluate the effect of 3 months vs. 8 months of neoadjuvant hormonal therapy before conventional dose radiotherapy (RT) on disease-free survival using prostate-specific antigen PSA and biopsies as end points for clinically localized prostate cancer.. Between February 1995 and June 2001, 378 men were randomized to either 3 or 8 months of flutamide and goserelin before conventional-dose RT (66 Gy) at four participating centers. The median patient age was 72 years (range, 50-84 years). The stage distribution was 17% T1c, 35% T2a, 34% T2b-T2c, 13% T3-T4. The Gleason score (GS) was < or =6 in 51%, 7 in 38%, and 8-10 in 11%. The median baseline PSA level was 9.7 ng/mL (range, 1.3-189 ng/mL). Of the 378 men, 26% were low risk (Stage T1c-T2a, GS < or =6, PSA <10 ng/mL), 43% were intermediate risk (Stage T2b or GS 7 or PSA 10-20 ng/mL), and 31% were high risk (Stage T3 or GS 8-10 or PSA >20 ng/mL). The two arms were balanced in terms of age, GS, T stage, risk group, and presenting PSA level. The median follow-up was 44 months (range, 10-84 months), and 361 patients were available for evaluation.. The 8-month arm achieved a lower PSA level before starting RT (0.37 vs. 0.74 ng/mL, p < or =0.001) and had a greater downsizing of the prostate (mean volume 26.6 cm(3) vs. 30.5 cm(3), p < or =0.001). However, the actuarial freedom from failure rate (biochemical by American Society for Therapeutic Radiology and Oncology definition, local or distant) for the 3-month vs. 8-month arms at 3 years was 66% vs. 68% and by 5 years was 61% vs. 62%, respectively (p = 0.36). No statistically significant difference was noted in the types of failure between the two arms (crude final status): biochemical, 22.2% vs. 22.3%; local, 10.2% vs. 6.5%; and distant, 3.4% vs. 4.4% (p = 0.61). Two-year post-RT biopsies were done in 57% (n = 205). Negative biopsies were obtained in 68% of the 3-month and 77% of the 8-month patients; 18% and 14% had indeterminate biopsies and 14% and 9% were positive for residual cancer (p = 0.34) in the two arms, respectively. The median PSA level for nonfailing patients was 0.50 ng/mL in both the 3-months and 8-month arms. A suggestion of improvement was found in the 8-month arm for disease-free survival at 5 years for high-risk patients (39% vs. 52%) but did not achieve statistical significance.. A longer period of neoadjuvant hormonal therapy before standard-dose RT does not appear to confer a benefit in terms of disease-free survival or to alter failure patterns. Failure was delayed in the 8-month arm, but this advantage was lost by 5 years of follow-up. A suggestion of benefit was noted with a longer period of hormonal therapy for high-risk patients.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Prostate-Specific Antigen; Prostatic Neoplasms; Statistics, Nonparametric; Survival Rate

To investigate whether testosterone surges occur on repeat injections of 3.6 or 10.8 mg goserelin (Zoladex) depot and, if so, their extent.. Men with prostate cancer for whom hormonal therapy was indicated were randomized to open-label goserelin 3.6 mg every 28 days (n = 129) or 10.8 mg every 84 days (n = 118) for 48 weeks. Serum testosterone and luteinizing hormone levels were measured before repeat injection on day 1 of each treatment cycle and then on days 4 and 8. Surges were defined in three ways: type 1, simultaneous increase in both testosterone and luteinizing hormone to within the age-specific normal range; type 2, increase in testosterone to within the age-specific normal range; and type 3, elevation in testosterone from less than to greater than the castrate level (greater than 18.5 ng/dL).. Most patients did not experience a testosterone surge. Two patients (1.8%) in the 10.8-mg group had a type 1 surge after one repeat injection and two (1.6%) in the 3.6-mg group had a type 2 surge after one repeat injection. Type 3 surges occurred after one or more repeat injections in 34 (27.0%) and 20 (17.7%) patients in the 3.6-mg and 10.8-mg groups, respectively (P = 0.065); the mean surge (+/- standard deviation) was 11.2 ng/dL (+/-13.5) and 17.3 ng/dL (+/-24.6), respectively. No patient with a testosterone surge had clinical symptoms of a tumor flare reaction.. The testosterone levels were consistently maintained within the castrate range (18.5 ng/dL or less) in most (77.4%) patients receiving long-term 3.6 mg or 10.8 mg goserelin.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Palliative Care; Prostatic Neoplasms; Testosterone

Health related quality of life was assessed in patients with prostate cancer on androgen suppression therapy re-dosed based on serum testosterone, and observations were confirmed regarding the safety, efficacy and cost per patient treated with this method of re-dosing luteinizing hormone-releasing hormone agonists.. The study comprised 22 patients with prostate cancer prospectively enrolled in a control-crossover designed trial of dosing depot luteinizing hormone-releasing hormone agonist based on serum testosterone. Health related quality of life using the Expanded Prostate Index Composite and SF-36 instruments was the primary outcome assessed.. Median duration of castrate testosterone was 5.5 months (range 3.5 to 10). Longer durations of castrate testosterone significantly correlated with lower pretreatment serum testosterone and smaller body mass index. No significant change from nadir prostate specific antigen was observed during castrate duration. The yearly cost of care was significantly decreased using the method of re-dosing based on serum testosterone ($3,567.90 versus $7,135.80). Short-term overall health related quality of life and patient satisfaction were significantly improved over baseline measurements. However, by study completion overall health related quality of life was equivalent regardless of the dosing method.. Patient assessed health related quality of life improved in the short term and the cost of care decreased with no loss in the quality of care or patient satisfaction using serum testosterone as the trigger to re-dose 10.8 mg. goserelin in patients with prostate cancer on androgen suppression therapy.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cross-Over Studies; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Goserelin; Health Status; Humans; Injections; Male; Middle Aged; Patient Satisfaction; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Surveys and Questionnaires; Testosterone

The role of androgens in cardiovascular disease is uncertain. We aimed to determine the vascular effects of androgen suppression in men with prostate cancer. Arterial stiffness (or 'compliance') was measured in 16 men (71+/-9 years, mean+/-S.D.) prior to, and 3 months after, complete androgen suppression with gonadotrophin-releasing hormone analogues as treatment for prostate cancer. Fifteen control men (70+/-7 years) also had arterial stiffness studies at baseline and 3 months later. Two measures of arterial stiffness were employed: systemic arterial compliance (SAC) was measured by simultaneous recording of aortic flow and carotid artery pressure ('area method'), and pulse wave velocities (PWVs) were recorded with the 'Complior' system. The 16 cases underwent glucose-tolerance and fasting-lipids tests on both visits. After 3 months of testosterone suppression, there was a significant fall in SAC, which was not seen in the controls [mean change+/-S.E.M., -0.26+/-0.09 a.c.u. (arbitrary compliance unit) in the cases versus +0.06+/-0.11 in the controls; P =0.03). Central, but not peripheral, PWVs tended to increase in the cases (mean change+/-S.E.M. for aorto-femoral PWV, +0.5+/-0.4 m/s for cases versus -0.3+/-0.3 m/s for controls; P =0.08). After testosterone suppression, fasting insulin levels increased from 6.89+/-4.84 m-units/l to 11.34+/-8.16 m-units/l (mean+/-S.D.), total cholesterol increased from 5.32+/-0.77 mmol/l to 5.71+/-0.82 mmol/l and high-density lipoprotein cholesterol increased from 1.05+/-0.24 mmol/l to 1.26+/-0.36 mmol/l; P <0.005 for all. No significant change occurred in body-mass index, serum glucose, low-density lipoprotein cholesterol or triacylglycerol (triglyceride) levels. Our results indicate that loss of androgens in men leads to an increase in aortic stiffness and serum insulin levels, and may therefore adversely affect cardiovascular risk.

Topics: Aged; Androgen Antagonists; Anthropometry; Antineoplastic Agents, Hormonal; Aorta; Carotid Arteries; Compliance; Goserelin; Hemodynamics; Humans; Hyperinsulinism; Insulin; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Vascular Resistance

DNA ploidy has consistently been found to be a correlate of prostate cancer patient outcome. However, a minority of studies have used pretreatment diagnostic material and have involved radiotherapy (RT)-treated patients. In this retrospective study, the predictive value of DNA ploidy was evaluated in patients entered into Radiation Therapy Oncology Group protocol 8610. The protocol treatment randomization was RT alone versus RT plus short-course (approximately 4 months) neoadjuvant and concurrent total androgen blockade (RT+TAB).. The study population consisted of 149 patients, of whom 74 received RT alone and 75 received RT+TAB. DNA content was determined by image analysis of Feulgen stained tissue sections; 94 patients were diploid and 55 patients were nondiploid. Kaplan-Meier univariate survival, the cumulative incidence method, and Cox proportional hazards multivariate analyses were used to evaluate the relationship of DNA ploidy to distant metastasis and overall survival.. DNA nondiploidy was not associated with any of the other prognostic factors in univariate analyses. In Kaplan-Meier analyses, 5-year overall survival was 70% for those with diploid tumors and 42% for nondiploid tumors. Cox proportional hazards regression revealed that nondiploidy was independently associated with reduced overall survival. No correlation was observed between DNA ploidy and distant metastasis. The diminished survival in the absence of an increase in distant metastasis was related to a reduction in the effect of salvage androgen ablation; patients treated initially with RT+TAB and who had nondiploid tumors had reduced survival after salvage androgen ablation.. Nondiploidy was associated with shorter survival, which seemed to be related to reduced response to salvage hormone therapy for those previously exposed to short-term TAB.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Combined Modality Therapy; Diploidy; DNA, Neoplasm; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Proportional Hazards Models; Prostatic Neoplasms; Retrospective Studies; Salvage Therapy; Survival Rate

To determine the endocrine effects, efficacy and tolerability of the 3-month formulation of goserelin acetate ('Zoladex' 10.8-mg depot; 'Zoladex' is a trade mark of the AstraZeneca group of companies) in the treatment of patients with advanced prostate cancer.. Between February 1996 and October 1997, this open, multicentre study enrolled 120 patients with locally advanced (T3/4) or metastatic (N+ or M1) disease, or an increase in prostate-specific antigen (PSA) level after radical prostatectomy. Patients received goserelin acetate 10.8-mg depot every 12 weeks until clinical progression or interruption for adverse events or other reasons.. The mean testosterone concentrations were suppressed to the castration range (< or =2 nmol/l) after 4 weeks of treatment and remained suppressed throughout the study. In total, 99/115 (86%) patients had a serum PSA response, and the mean PSA value decreased significantly during treatment (p = 0.006). The mean PSA level at baseline was significantly lower in patients without disease progression compared to those who experienced disease progression (p = 0.0002). Goserelin acetate 10.8-mg depot was well tolerated and there were no injection site reactions.. The goserelin acetate 10.8-mg depot is well tolerated with no injection site reactions. It produces PSA responses and provides reliable suppression of serum testosterone.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Male; Middle Aged; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Testosterone

Luteinising hormone releasing hormone (LHRH) analogues are routinely used in the treatment of patients with advanced prostate cancer. This randomised crossover trial was conducted to compare patient comfort and tolerability between two commonly used LHRH analogues: goserelin acetate and leuprorelin acetate. A total of 50 patients were randomised into two groups, each receiving 6-monthly injections of leuprorelin acetate (a liquid presentation) and goserelin acetate (a depot pellet) and crossing over between treatments. Patients completed a simple visual analogue score for the discomfort felt from the injections. An analysis of variance model was used, and the results found that patients do tolerate leuprorelin acetate (0.589) better than goserelin acetate (1.343) (P < 0.001, CI = 95%).

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cross-Over Studies; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Leuprolide; Male; Middle Aged; Pain; Prostatic Neoplasms

To determine the acceptability of short term neo-adjuvant maximal androgen deprivation (MAD) to patients treated with external beam radiation for locally advanced prostate cancer.. Between 1996 and 2000, 818 patients with locally advanced, but non-metastatic, prostate cancer were entered into a randomised clinical trial (TROG 96.01), which compared radiation treatment alone with the same radiation treatment and 3 or 6 months neo-adjuvant MAD with goserelin and flutamide. Relevant symptoms, and how troublesome they were to the patient, were scored using a self-assessment questionnaire. This was completed by the patient at registration, and at specified times during and after treatment. Patients taking flutamide had liver function tests checked at regular intervals.. All patients have completed at least 12 months follow-up after treatment. Nearly all patients completed planned treatment with goserelin, but 27% of patients in the 6-month MAD treatment arm, and 20% in the 3-month arm, had to stop flutamide early. This was mainly due to altered liver function (up to 17% patients) and bowel side effects (up to 8% patients). However, although flutamide resulted in more bowel symptoms for patients on MAD, there was significant reduction in some urinary symptoms on this treatment. Acute bowel and urinary side effects at the end of radiation treatment were similar in all treatment arms. Side effect severity was unrelated to radiation target volume size, which was reduced by MAD, but symptomatology prior to any treatment was a powerful predictor. Of the 36% of patients who were sexually active before any treatment, the majority became inactive whilst on MAD. However, sexual activity at 12 months after radiation treatment was similar in all treatment arms, indicating that the effects of short term MAD on sexual function are reversible.. Despite temporary effects on sexual activity, and compliance difficulties with flutamide, short-term neo-adjuvant MAD was not perceived by patients to be a major inconvenience. If neo-adjuvant MAD in the way tested can be demonstrated to lead to improved biochemical control and/or survival, then patients would view these therapeutic gains as worthwhile. Compliance with short-term goserelin was excellent, confirming that LH-RH analogues have a potential role in more long-term adjuvant treatment. However, for more protracted androgen deprivation, survival advantages and deleterious effects need to be assessed in parallel, in order to determine the optimal duration of treatment.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Erectile Dysfunction; Flutamide; Goserelin; Humans; Intestines; Male; Middle Aged; Neoadjuvant Therapy; Prostatic Neoplasms; Surveys and Questionnaires; Treatment Outcome; Urinary Bladder

We compare the cytoreductive efficacy of bicalutamide or goserelin with no hormonal manipulation in prostate cancer before brachytherapy.. Transrectal ultrasound volume estimations were performed in clinic and during the brachytherapy-planning scan. Between volume estimations, patients received no hormonal treatment, bicalutamide 150 mg once daily or goserelin 3.6 mg every 28 days.. Patients receiving no hormonal manipulation had a volume increase of 8% compared with an 8% volume reduction in the bicalutamide group and a 26% reduction in the goserelin group. As initial prostate volume was not equivalent in the three groups, a subgroup analysis was performed on patients who received active treatment for more than 3 months who had initial prostate volume less than 55 cm3. In this subgroup, a mean fall in prostate volume of 7%, occurred in the bicalutamide group compared with 21% in the goserelin group. In both the original and subgroup analysis, the cytoreductive efficacy of goserelin was significantly greater than bicalutamide (P < 0.0001).. In the absence of data from randomised trials, comparing the efficacy of these agents, luteinising hormone-releasing hormone (LHRH) analogues remain the gold standard for cytoreduction before prostate brachytherapy. If the neoadjuvant efficacy of hormonal manipulation in external beam radiotherapy is dependent on prostate volume reduction, then LHRH analogues may also prove more effective in this neoadjuvant role.

Topics: Analysis of Variance; Anilides; Goserelin; Humans; Male; Middle Aged; Nitriles; Premedication; Prospective Studies; Prostate; Prostatic Neoplasms; Rectum; Tosyl Compounds; Ultrasonography

Radiation Therapy Oncology Group (RTOG) Protocol 92-02 was a randomized trial testing long-term (LT) adjuvant androgen deprivation (AD) after initial AD with external-beam radiotherapy (RT) in patients with locally advanced prostate cancer (PC; T2c-4) and with prostate-specific antigen level less than 150 ng/mL.. Patients received a total of 4 months of goserelin and flutamide, 2 months before and 2 months during RT. A radiation dose of 65 to 70 Gy was given to the prostate and a dose of 44 to 50 Gy to the pelvic lymph nodes. Patients were randomly assigned to receive no additional therapy (short-term [ST]AD-RT) or 24 months of goserelin (LTAD-RT); 1,554 patients were entered onto the study.. The LTAD-RT arm showed significant improvement in all efficacy end points except overall survival (OS; 80.0% v 78.5% at 5 years, P =.73), compared with the STAD-RT arm. In a subset of patients not part of the original study design, with tumors assigned Gleason scores of 8 to 10 by the contributing institutions, the LTAD-RT arm had significantly better OS (81.0% v 70.7%, P =.044). There was a small but significant increase in the frequency of late radiation grades 3, 4, and 5 gastrointestinal toxicity ascribed to the LTAD-RT arm (2.6% v 1.2% at 5 years, P =.037), the cause of which is not clear.. The RTOG 92-02 trial supports the addition of LT adjuvant AD to STAD with RT for T2c-4 PC. In the exploratory subset analysis of patients with Gleason scores 8 to 10, LT adjuvant AD resulted in a survival advantage.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Drug Administration Schedule; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Radiation Dosage; Survival Analysis; Treatment Outcome

We did a randomised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone (LHRH) to investigate the added value of long-term androgen suppression in locally advanced prostate cancer.. Between 1987 and 1995, 415 patients were randomly assigned radiotherapy alone or radiotherapy plus immediate androgen suppression. Eligible patients had T1-2 tumours of WHO grade 3 or T3-4 N0-1 M0 tumours; the median age of participants was 71 years (range 51-80). In both treatment groups, 50 Gy radiation was delivered to the pelvis over 5 weeks, and 20 Gy over 2 weeks as a prostatic boost. Goserelin (3.6 mg subcutaneously every 4 weeks) was started on the first day of irradiation and continued for 3 years; cyproterone acetate (150 mg orally) was given for 1 month starting 1 week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analyses were by intention to treat.. 412 patients had evaluable data, with median follow-up of 66 months (range 1-126). 5-year clinical disease-free survival was 40% (95% CI 32-48) in the radiotherapy-alone group and 74% (67-81) in the combined-treatment group (p=0.0001). 5-year overall survival was 62% (52-72) and 78% (72-84), respectively (p=0.0002) and 5-year specific survival 79% (72-86) and 94% (90-98).. Immediate androgen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Disease-Free Survival; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Time Factors

It is known that bone mineral density (BMD) is low in men who are hypogonadal. However, the rate and sites of bone loss following testosterone deficiency are not known. The resulting hypogonadism after GnRH analog therapy for the treatment of prostate cancer allows us to examine bone loss and bone resorption immediately after testosterone withdrawal. Therefore, we examined the effects of GnRH analog treatment on bone loss and bone resorption in men with prostate cancer. BMD and serum and urine concentrations of markers of bone turnover were determined in men with prostate cancer and in age-matched controls. Measurements were taken before GnRH therapy and 6 and 12 months after instituting therapy. After 12 months of GnRH therapy, the BMD of the total hip and ultra distal radius decreased significantly (P < 0.001) in men with prostate cancer compared with the controls. The mean bone loss was 3.3% and 5.3%, respectively. The observed reduction in BMD in the spine (2.8%) and the femoral neck (2.3%) did not reach statistical significance. No significant bone loss was observed in the control subjects. The concentration of the urine marker of bone resorption, N-telopeptide, was significantly increased from baseline and from controls at both 6 and 12 months in patients treated with GnRH analog therapy compared with control subjects (P < 0.05). The concentration of a serum marker of bone formation, bone-specific alkaline phosphatase, was not significantly different from baseline or from controls at 6 and 12 months. Thus, the decreased total hip and ultra distal radius BMD and increased urinary N-telopeptide concentration after testosterone withdrawal demonstrate an increase in trabecular bone loss and enhanced bone resorption. These findings demonstrate a significant loss of bone in men with prostate cancer after receiving GnRH therapy and suggest that the total hip and radius are the preferred sites for monitoring bone loss in older men. In addition, markers of bone resorption may be helpful.

Topics: Absorptiometry, Photon; Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Bone Density; Femur Neck; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hypogonadism; Male; Osteoporosis; Prospective Studies; Prostatic Neoplasms; Radius

To report the first systematic investigation of the cognitive effects of luteinizing hormone-releasing hormone (LHRH) analogues in male patients, as LHRH analogues have been associated with memory impairments in women using these drugs for gynaecological conditions.. Eighty-two men with extraprostatic prostate cancer were randomly assigned to receive either continuous leuprorelin, goserelin (both LHRH analogues), cyproterone acetate (a steroidal antiandrogen) or close clinical monitoring. These patients underwent cognitive assessments at baseline and before starting treatment (77), and then 6 months later (65).. Compared with the baseline assessments, men receiving androgen suppression monotherapy performed worse in two of 12 tests of attention and memory; 24 of 50 men randomized to active treatment and assessed 6 months later had a clinically significant decline in one or more cognitive tests but not one patient randomized to close monitoring showed a decline in any test performance.. Pharmacological androgen suppression monotherapy for prostate cancer may be associated with impaired memory, attention and executive functions.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cognition Disorders; Cyproterone Acetate; Drug Combinations; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms

It is unclear whether positive interactions between radiation and androgen withdrawal for patients with locally advanced prostate cancer is synergistic or additive. The present study aimed to clarify the significance of neoadjuvant androgen ablation prior to external radiotherapy in a human prostate LNCaP tumor model and in patients with locally advanced prostate cancer.. Comparisons were made between the effect of castration prior to radiation on the growth of subcutaneous LNCaP tumors implanted into male nude mice and their serum prostate-specific antigen (PSA) levels, and the results of castration or radiation alone. Twenty-nine patients with histologically proven and locally advanced adenocarcinoma of the prostate were treated with luteinizing hormone-releasing hormone analog at least 3 months before, during, and after external radiation therapy with a total dose of 70 Gy. The toxicity and response to this therapy were evaluated.. Treatment combining castration and radiation resulted in synergistic inhibition of LNCaP tumor growth and a significant delay in the emergence of androgen-independent recurrence as opposed to either treatment alone. The external radiotherapy was completed in 28 patients (96.6%), resulting in a reduction of serum PSA levels in all 28 patients to below 1.0 ng/mL. All patients were alive after a mean follow-up period of 34 months (range 11-53) with a 3-year PSA relapse-free survival rate of 83.7%. Among several factors examined, only the Gleason score was significantly associated with PSA relapse-free survival in univariate analysis, but not in multivariate analysis. Thirteen of 28 patients (46%) and 7 of 28 (25%) also showed at least one form of gastrointestinal or genitourinary toxicity, respectively. Of these patients, 8 with gastrointestinal toxicities, and 1 with genitourinary toxicity, experienced acute complications higher than grade 3.. The experimental findings objectively suggested the use of neoadjuvant androgen withdrawal prior to radiation therapy. Although our clinical experience is preliminary, combined androgen ablation and radiation therapy may also be effective in controlling locally advanced prostate cancer, with tolerable side-effects.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Animals; Antineoplastic Agents, Hormonal; Disease Models, Animal; Goserelin; Humans; In Vitro Techniques; Leuprolide; Male; Mice; Mice, Inbred BALB C; Middle Aged; Neoadjuvant Therapy; Orchiectomy; Prostatic Neoplasms; Tumor Cells, Cultured

To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade in advanced prostatic cancer.. Previously untreated patients with histologically proven stage C or D (American Urological Association Staging System) disease were randomly allocated to either bicalutamide (B) or goserelin plus flutamide (G+F). After disease progression, patients treated with B were assigned to castration. The primary endpoint for this trial was overall survival. Prostate cancer-specific survival and progression were included among secondary endpoints.. In total 108 patients received B and 112 received G+F. At a median follow-up time of 54 months (range 1-89), 151 patients progressed and 113 died. There was no significant difference in the duration of either progression-free or overall survival. Hazards of progression, death and cancer-specific death, corrected by disease stage, tumor grade and baseline PSA level, showed that patients initially assigned to B had a higher risk of progression but a comparable risk of death and cancer-specific death with the exception of patients with G3 tumors who had an increased risk of death).. In patients with well or moderately well differentiated tumors, B monotherapy followed by castration may offer the same survival chance as maximal androgen deprivation. In those patients it thus represents a reasonable choice that can avoid the side effects of androgen deprivation for considerable periods of time.

Topics: Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Flutamide; Goserelin; Humans; Male; Middle Aged; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis; Tosyl Compounds; Treatment Outcome

To compare, by a secondary analysis, the therapeutic benefits of androgen suppression in protocol prostate cancer patients with relapse after radiotherapy (RT) for locally advanced disease who, in the Phase III trial beginning in 1987, were assigned to receive or not receive a short course of neoadjuvant maximal androgen suppression before definitive RT.. Between 1987 and 1991, 456 patients were entered in the Radiation Therapy Oncology Group trail 86-10 and randomized to receive (Arm I) or not to receive (Arm II) neoadjuvant hormonal therapy (HT), which was 4 months of goserelin (3.6 mg every 4 weeks) and flutamide (250 mg t.i.d.) before and during RT for bulky T2-T4 tumors. The overall and disease-specific survival after both randomization and salvage HT for patients with relapse was evaluated, as well as the duration of response in those patients undergoing salvage HT. The outcomes in patients who had received neoadjuvant HT vs. those who had not were compared. The median follow-up after randomization for all alive patients was 9.0 years and was 5.5 years for alive patients after beginning salvage HT.. Fewer patients received salvage HT on Arm I than on Arm II (45% vs. 63%, p <0.001). The outcomes by randomized treatment arm (I vs. II) from the time of beginning salvage HT were similar. At 5 years after salvage HT, the overall survival rates were 41% and 41% and the disease-specific survival rates were 50% and 50%. At 8 years after randomization, the overall survival rates were 47% and 44% and the disease-specific survival rates were 55% and 56%.. Although a 4-month course of neoadjuvant and concurrent maximum androgen suppression and RT (compared with RT alone) significantly increases the freedom from relapse rate and freedom from receiving salvage HT, it does not compromise the long-term beneficial effect of subsequent salvage HT, if needed for relapse. These findings with long follow-up in patients treated for locally advanced disease diagnosed 9-14 years previously should help allay concerns of the possible development of "resistance" to androgen suppression when 4-month courses of neoadjuvant HT are used before primary treatment.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Disease-Free Survival; Flutamide; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Recurrence; Salvage Therapy; Time Factors; Treatment Outcome

Low androgen levels in men are associated with increased cardiovascular risk, through unclear mechanisms. We measured arterial stiffness ('compliance') in 21 men receiving complete testosterone suppression therapy for prostate cancer, and in 25 controls. Systemic arterial compliance (SAC), which assesses proximal aortic stiffness, was calculated by simultaneous recording of aortic flow and carotid artery pressure (the 'area method'). Aorto-femoral (A-F), aorto-radial (A-R) and femoral-dorsalis pedis (F-DP) pulse-wave velocities (PWVs) were recorded using the 'Complior' system. SAC was significantly lower in the androgen-depleted men compared to controls (0.81 +/- 0.53 vs. 1.18 +/- 0.43 arbitrary compliance units, p = 0.01, mean +/- SD). Correspondingly, their A-F PWV was higher (14.1 (10.1-21.8) vs. 12.4 (9.6-17.4) m/s, p = 0.03, median (range)). Cases tended to be older (75 +/- 7 vs. 71 +/- 6 years, p = 0.07), and to have higher systolic blood pressure (148 +/- 22 vs. 143 +/- 17 mmHg, p = 0.40); however, SAC was still significantly lower (p = 0.03) after adjustment for age and stratification for central systolic pressure (< or = or > the median). Adjustment of A-F PWV for age and central systolic pressure reduced significance to p = 0.07. There was no significant difference in peripheral PWVs between groups. In conclusion, testosterone suppression is associated with increased aortic stiffness, only partly explained by age and blood pressure. Loss of androgens in men might therefore adversely affect cardiovascular risk.

Topics: Age Factors; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Arteries; Cardiovascular Diseases; Flutamide; Goserelin; Hemodynamics; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Vascular Patency

The aim of this study was to compare the efficacy of total intermittent androgen deprivation (IAD) versus total continuous androgen deprivation (CAD) for treating patients with advanced prostate cancer in a phase III randomized trial. A total of 68 evaluable patients with hormone-naive advanced or relapsing prostate cancer were randomized to receive combined androgen blockade according to a continuous (n = 33) or intermittent (n = 35) regimen. Therapeutic monitoring was assessed by use of serum prostate-specific antigen (PSA) measurements. Patients in the CAD and IAD groups were equally stratified for age, biopsy Gleason score, and baseline serum PSA levels. The outcome variable was time to androgen-independence of the tumor, which was defined as increasing serum PSA levels despite androgen blockade. Mean follow-up was 30.8 months. The 35 IAD-treated patients completed 91 cycles, and 19 of them (54.3%) completed > or = 3 cycles. Median cycle length and percentage of time off therapy were 9.0 months and 59.5, respectively. The estimated 3-year progression rate was significantly lower in the IAD group (7.0% +/- 4.8%) than in the CAD group (38.9% +/- 11.2%, P = 0.0052). Our data suggest that IAD treatment may maintain the androgen-dependent state of advanced human prostate cancer, as assessed by PSA measurements, at least as long as CAD treatment. Further studies with longer follow-up times and larger patient cohorts are needed to determine the comparative impacts of CAD and IAD on survival.

Topics: Adenocarcinoma; Administration, Oral; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease Progression; Drug Administration Schedule; Flutamide; Goserelin; Humans; Injections, Subcutaneous; Male; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms

Phase III studies have demonstrated the clinical benefit of adding neo-adjuvant androgen deprivation to radical radiotherapy for clinically localised prostate cancer. We have developed a nomogram to describe the probability of PSA control for patients treated in this way. Five hundred and seventeen men with clinically localised prostate cancer were treated with 3-6 months of neo-adjuvant androgen deprivation and radical radiotherapy (64Gy in 32#) between 1988 and 1998. Median presenting PSA was 20 ng x ml(-1), and 56% of patients had T3/4 disease. Multivariate analysis of pre-treatment factors was performed, and a nomogram developed to describe PSA-failure-free survival probability. At a median follow-up of 44 months, 233 men had developed PSA failure. Presenting PSA, histological grade and clinical T stage were all highly predictive of PSA failure on multivariate analysis. The nomogram score for an individual patient is given by the summation of PSA (<10=0, 10-19=16, 20-49=44, > or =50=100), grade (Gleason 2-4=0, 5-7=44, 8-10=81) and T stage (T1/2=0, T3/4=35). For a nomogram score of 0, 50, 100 and 150 points the 2 year PSA control rate was 93, 87, 75 and 54%, and the 5 year PSA control rate was 82, 67, 44 and 18%. These results are comparable to those using surgery or higher doses of radical radiotherapy alone. The nomogram illustrates the results of multivariate analysis in a visually-striking way, and facilitates comparisons with other treatment methods.

Topics: Administration, Oral; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Cyproterone Acetate; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Patient Care Planning; Predictive Value of Tests; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Treatment Outcome

The problem of estimating expected outcomes for the economic evaluation of treatments for which the outcome of principal interest is (quality adjusted) survival time has so far not received sufficient attention in the literature. The best estimate of expected survival is mean survival time, but with censored survival data, the true survival time for all the subjects is not known, so the mean is not defined.A possible solution to this estimation problem is illustrated by a retrospective cost-effectiveness analysis of the addition of hormonal therapy to standard radiotherapy for patients with locally advanced prostate cancer. A recently proposed method is used to approach the problem caused by censored cost data, and the impact of uncertainty is assessed by bootstrap resampling techniques. Mean survival time is estimated by a restricted means analysis with the time point of restriction determined by statistical criteria. When average total costs and mean survival time is evaluated at this time point of restriction, the result is that the combined therapy (radiotherapy plus hormonal therapy) increases mean survival time by about 1 year, while reducing the costs per patient for the French health insurance system by 12 700 FF. The time point of restriction may also be determined by other criteria and mean survival time may be estimated by extrapolating the survival curves by means of various parametric survival distributions. We show that the exact results of the economic evaluation are decisively determined by the restriction time point chosen and the approach taken to estimate mean survival time.

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Cost-Benefit Analysis; Drug Costs; France; Goserelin; Health Care Costs; Humans; Male; Models, Statistical; Neoplasm Staging; Prognosis; Proportional Hazards Models; Prostatic Neoplasms; Quality-Adjusted Life Years; Survival Analysis; Treatment Outcome

To investigate the possibility that more complete blockade of androgens or combined androgen blockade (CAB) could lead to even longer term control of localized prostate cancer. A series of recent studies have shown important benefits on survival using medical or surgical castration in localized or locally advanced prostate cancer.. The effect of CAB on long-term control or possible cure of prostate cancer was evaluated by the absence of biochemical failure or prostate-specific antigen (PSA) rise for at least 5 years after cessation of continuous treatment. A total of 57 patients with localized or locally advanced disease received CAB for periods ranging from 1 to 11 years. Twenty patients with Stage B2/T2 prostate cancer who were treated for a median duration of 7.2 years (range 2.8 to 11.7) with CAB stopped treatment and were followed up for a median of 4.9 years. Eleven patients with Stage B2/T2 also received CAB but for only 1 year. Twenty-six patients with Stage C/T3 treated with continuous CAB for a median of 9.9 years (range 3.8 to 11.3) with undetectable PSA levels stopped treatment and were followed up for a median of 5.6 years. The median follow-up since diagnosis was 14.6 years for patients with Stage B2/T2 and 16.4 years for patients with Stage C/T3 disease.. With a minimum of 5 years of follow-up after cessation of long-term CAB, two PSA rises occurred among 20 patients with Stage T2-T3 cancer who stopped treatment after continuous CAB for more than 6.5 years, for a nonfailure rate of 90%. For the 11 patients who had received CAB for 3.5 to 6.5 years, the nonfailure rate was only 36%. The serum PSA increased within 1 year in all 11 patients with Stage B2/T2 treated with CAB for only 1 year, thus indicating that active cancer remained present after short-term androgen blockade despite undetectable PSA levels. In all patients who had biochemical failure after stopping CAB, the serum PSA level rapidly decreased again to undetectable levels when CAB was restarted and remained at such low levels afterward. Of these patients, only 1 patient had died of prostate cancer at last follow-up.. The present data suggest that long-term and continuous CAB offers the possibility of long-term control or possible cure of localized prostate cancer.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Therapy, Combination; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Longitudinal Studies; Male; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome; Triptorelin Pamoate

To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study.. Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade.. Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment.. Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Biopsy; Chemotherapy, Adjuvant; Drug Administration Schedule; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nitriles; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Tosyl Compounds

To determine the potential advantage of androgen ablation following standard external-beam radiation therapy in patients with locally advanced (clinical or pathologic T3; clinical or pathologic node positive) carcinoma of the prostate.. In 1987 the RTOG initiated a Phase III trial of long-term adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients were accrued to the study of which 945 remain analyzable: 477 on the adjuvant hormone arm (Arm I); and 468 on the radiation only arm (Arm II) with hormones initiated at relapse. The initial results were reported in the Journal of Clinical Oncology in 1997.. With a median follow up of 5.6 years for all patients and 6.0 years for living patients local failure at 8 years was 23% for Arm I and 37% for Arm II (p < 0.0001). Distant metastasis was likewise favorably impacted with the immediate use of hormonal manipulation with a distant metastasis rate in Arm I of 27% and 37% in Arm II (p < 0.0001). Disease-free survival (NED survival) and NED survival with PSA of 1.5 ng/mL (bNED) or less were both statistically significant in favor of the immediate hormone arm (both p < 0.0001). Cause-specific failure was not statistically different with a cause-specific failure of 16% for Arm I and 21% in Arm II (p = 0.23). Overall survival was likewise not statistically different between two arms, with a 49% overall survival at 8 years in Arm I and 47% in Arm II (p = 0.36). Subset analysis of centrally reviewed Gleason 8-10 patients who did not undergo prostatectomy showed that for patients receiving radiation therapy plus adjuvant hormones there was a statistically significant improvement in both absolute (p = 0.036) and cause-specific survival (p = 0.019).. Use of long-term adjuvant androgen deprivation in addition to definitive radiation therapy results in a highly significant improvement in regards to local control, freedom from distant metastasis, and biochemical free survival in unfavorable prognosis patients with carcinoma of the prostate.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Disease-Free Survival; Follow-Up Studies; Goserelin; Humans; Male; Neoplasm Staging; Prognosis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy Dosage; Survival Analysis; Treatment Failure

The benefit of adjuvant hormones in prostate cancer patients receiving definitive radiation therapy (RT) in RTOG 85-31 and 86-10 has previously been reported. This analysis excludes those patients with positive lymph nodes or postprostatectomy to determine the benefit of adjuvant hormones in men with locally advanced nonmetastatic prostate cancer receiving definitive RT.. Nine hundred ninety-three eligible patients from RTOG 85-31 and 86-10 treated between 1987-1992 were included in this study. Five hundred seventy-five patients with T3N0M0 disease were included from RTOG 85-31 and 418 patients with T2b-T4N0M0 disease from RTOG 86-10. Patients randomized to receive long-term hormones (LTH) on 85-31 received goserelin starting the last week of RT and continued indefinitely. Patients treated with short-term hormones (STH) on 86-10 received goserelin and flutamide 2 months prior to and during RT. The median follow-up for all patients in this analysis was 71 months (range, 0.6-129 months).. Combining both studies, statistically significant improvements in outcome were observed between the RT and hormones (I) and RT alone (II) groups for biochemical disease-free survival (bNED control) and distant metastases failure (DMF). Statistically significant improvements in bNED control, DMF and cause-specific failure (CSF) were observed for patients receiving LTH compared with STH. In those patients receiving LTH, the benefit in bNED control (p = 0.0002), DMF (p = 0.05), and CSF (p = 0.02) was limited to centrally reviewed Gleason score of 7 and 8-10 tumors. For all patients treated on 85-31, statistically significant improvements for bNED control, DMF, and CSF were observed between Group I and II. Multivariate analysis demonstrated Gleason score and the use of LTH to be independent predictors for bNED control (p < 0.0001), DMF (p < 0.0001), and CSF (p < 0.002).. Based on this analysis, adjuvant long-term hormones compared to short-term hormones resulted in statistically significant improvements in bNED control, DMF, and CSF rates for patients with locally advanced nonmetastatic prostate cancer.

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Goserelin; Humans; Male; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Radiotherapy Dosage; Treatment Failure

To determine the effectiveness of triple androgen blockade as an alternative to watchful waiting, radical prostatectomy or radiation therapy in the management of patients with clinical stage T1 to T3 prostate cancer.. The records of 110 consecutive patients were retrospectively evaluated. Patients were treated with a three-drug androgen blockade regimen, consisting of a luteinizing hormone-releasing hormone agonist (leuprolide or goserelin) plus an antiandrogen (flutamide or bicalutamide) plus finasteride (a 5-alpha-reductase inhibitor), followed by finasteride maintenance therapy, as the sole intervention. All patients refused local therapy and had their prostates intact. Determinants of efficacy included serum prostate-specific antigen (PSA) levels and disease-specific survival.. Patients were treated for a median of 13 months with triple androgen blockade. At baseline, mean PSA level was 13.2 +/- 1.2 ng/ml (range, 0.39-100 ng/ml), and mean Gleason score was 6.6 +/- 0.1 (range, 4-10). During treatment, PSA levels declined to < or =0.1 ng/ml in all patients, with a median time of 3 months. After a median follow-up of 36 months since initiation of treatment, PSA levels have remained stable in 105 of 110 patients (95.5%). At a median follow-up of 55 months (range, 38-125 months), the mean PSA level for the first 57 patients treated in this series is 1.88 +/- 0.1 (range, 0-11.0 ng/ml). Only 9 of 110 (8.1%) patients have a PSA level > or =4.0 ng/ml. To date, no patient has received a second cycle of hormone blockade.. Although median follow-up is short, triple androgen blockade therapy followed by finasteride maintenance appears to be a promising alternative for the management of patients with clinically localized or locally advanced prostate cancer. Further study of this approach is warranted.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Finasteride; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

We contrasted the endocrinological and biochemical efficacies of abarelix depot, a pure gonadotropin-releasing hormone antagonist, with a prospective concurrent control cohort receiving luteinizing hormone releasing hormone (LH-RH) agonists with or without antiandrogen for treatment of patients with prostate cancer receiving initial hormonal therapy.. In this phase 2 open label study 242 patients with prostate cancer requiring initial hormonal treatment received abarelix depot (209) or LH-RH agonists (33) with or without antiandrogen. A total of 100 mg. abarelix depot was delivered intramuscularly every 28 days with an additional injection on day 15. LH-RH agonists with or without antiandrogen were administered according to the depot formulation used. Endocrine efficacy was measured by the absence of testosterone surge and rapidity of castration onset. The rate of prostate specific antigen decrease was assessed.. No patient treated with abarelix depot had testosterone surge during week 1 compared with 82% of those treated with LH-RH agonists. The concomitant administration of antiandrogen had no effect. During the first week of drug administration, in 75% of patients treated with abarelix depot and in 0% of those treated with LH-RH agonist medical castration was achieved. Prostate specific antigen decrease was faster, with no flare or surge in patients treated with abarelix depot. Abarelix depot was well tolerated.. Abarelix depot represents a new class of hormonal therapy, gonadotropin releasing hormone antagonists, that has rapid medical castration and avoids the testosterone surge characteristic of LH-RH agonists.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Dihydrotestosterone; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Intramuscular; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Oligopeptides; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testis; Testosterone

Pharmacodynamics (PD), anti-tumor effects, safety and pharmacokinetics of a 3-month formulation of goserelin (Zoladex LA 10.8 mg depot: "10.8 mg depot") were investigated in a collaborative multicenter study. Study participants were 40 Japanese patients with prostate cancer comprising 20 untreated patients and 20 switch patients who had been receiving Zoladex 3.6 mg depot for 3 months or longer. Serum testosterone levels, serum LH levels, prostate-specific antigen (PSA) levels and drug concentrations were measured until 12 weeks after a single subcutaneous dose of 10.8 mg depot. Anti-tumor effects were evaluated by means of changes in the tumor lesions and the PSA levels at 12 weeks. After administration to the untreated patients, 10.8 mg depot reduced serum testosterone to the castrate range within 4 weeks and the reduction was maintained for up to 12 weeks. In the switch patients, serum testosterone suppression that had been produced by previous treatment with Zoladex 3.6 mg depot was maintained for up to 12 weeks following 10.8 mg depot administration. The anti-tumor effect at 12 weeks was 90.0% including partial response cases. The ratio of PSA normalization at 12 weeks was 75.0%. Fifty-seven adverse reactions were observed in 27 of the 40 patients (67.5%), but none were clinically significant. Although a disease flare presented as urinary retention in 1 of the untreated patients, all patients completed the study. Serum goserelin was detected up to 12 weeks after the administration of 10.8 mg depot. In conclusion a single dose of 10.8 mg depot showed a satisfactory PD-effect and brought about clinical efficacy persisting for at least 12 weeks and was well tolerated in patients with prostate cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Drug Administration Schedule; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Testosterone

To test the hypothesis that androgen ablation before and during radiotherapy for locally advanced carcinoma of the prostate may, by reducing tumor bulk and enhancing tumor cell kill, improve locoregional control and ultimately survival.. The study was conducted from 1987 to 1991. Eligible patients were those with bulky tumors (T2--T4) with or without pelvic lymph node involvement and without evidence of distant metastases. They were randomized to receive goserelin, 3.6 mg every 4 weeks; and flutamide, 250 mg t.i.d. for 2 months before radiation therapy and during radiation therapy (Arm I), or radiation therapy alone (Arm II). Of 471 randomized patients, 456 were evaluable: 226 on Arm I and 230 on Arm II.. As of November 1999, the median follow-up has reached 6.7 years for all patients and 8.6 years for alive patients. At 8 years, androgen ablation has been associated with an improvement in local control (42% vs. 30%, p = 0.016), reduction in the incidence of distant metastases (34% vs. 45%, p = 0.04), disease-free survival (33% vs. 21%, p = 0.004), biochemical disease-free survival = PSA <1.5 (24% vs. 10%, p < 0.0001), and cause-specific mortality (23% vs. 31%, p = 0.05). However, subset analysis indicates that the beneficial effect of short-term androgen ablation appears preferentially in patients with Gleason score 2--6. In that population, there is a highly significant improvement in all endpoints, including survival (70% vs. 52%, p = 0.015). In patients with Gleason 7--10 tumors, the regimen has not resulted in a significant enhancement in either locoregional control or survival.. In patients with Gleason score 2--6 carcinoma of the prostate, a short course of androgen ablation administered before and during radiotherapy has been associated with a highly significant improvement in local control, reduction in disease progression, and overall survival.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cause of Death; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Life Tables; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Prostatic Neoplasms; Radiotherapy, High-Energy; Survival Analysis; Treatment Outcome

We present a retrospective cost-effectiveness analysis using data from a randomised controlled trial (EORTC 22863) of the addition of early hormonal therapy with a luteinising hormone-releasing hormone (LHRH) analogue to radiotherapy in the treatment of patients with locally advanced prostate cancer. Data on the use of medical resources were extracted from the hospital charts of 90 patients recruited into the trial by one French hospital. Costs are assessed from the viewpoint of the French healthcare financing system and adjusted for censoring. Expected costs per patient of each treatment is related to the expected outcome, mean survival time, estimated by a restricted means analysis. The time point of restriction is determined by statistical criteria. In the base case analysis with a cut-off time point at 8.58 years, the combined therapy group (COMB) had a gain in mean survival time of 1.06 years (7.05 versus 5.99 years) and a reduction of average total costs of 12700 French francs (FF) (58300 FF versus 71000 FF). The analysis of uncertainty uses bootstrap techniques with 5000 replicates to examine the joint distribution of cost and survival outcomes. In 76% of the cases, COMB results in longer mean survival time and lower costs than the radiotherapy group (RT). In cases where COMB therapy raises costs (13% of the cases), it is rarely by more than 20000 FF per patient, no matter the size of the associated survival gain. It is thus highly likely that COMB should be considered a cost-effective option compared with RT for these patients. The exact result of the economic evaluation is decisively determined by the restriction time point selected for the determination of mean survival time, partly also because the average total costs of the two treatments develop entirely differently as a function of the survival time.

Topics: Antineoplastic Agents, Hormonal; Combined Modality Therapy; Cost-Benefit Analysis; Follow-Up Studies; France; Goserelin; Health Care Costs; Humans; Male; Prostatic Neoplasms; Retrospective Studies; Survival Rate

An increasingly important issue in the management of prostate cancer is the occurrence of biochemical failure (ie, increasing serum prostate-specific antigen [PSA] levels) in patients with clinically localized prostate cancer who initially underwent definitive treatments with curative intent (prostatectomy and/or radiation therapy). This pilot trial evaluated chemotherapy followed by hormone therapy for a defined period in patients with biochemical (and possibly clinical) recurrence after initial local therapies for localized/locally advanced prostate cancer. Patients who developed increasing PSA > 4 ng/mL after initial prostatectomy and/or radiation therapy received docetaxel, 70 mg/m(2) every 3 weeks for up to 6 courses, followed by 4 months of total androgen suppression (using a luteinizing hormone-releasing hormone agonist plus bicalutamide, 50 mg/d) and 8 months of peripheral androgen blockade (using finasteride, 5 mg/d, plus bicalutamide, 50 mg/d). Twenty-seven patients have enrolled to date, 23 of whom received four or six cycles of docetaxel before hormonal therapies. Seventeen (74%) of 23 patients who completed four to six cycles of chemotherapy had a > or =40% decrease in PSA, and 16 (89%) of 18 patients who completed 4 months of total androgen suppression achieved PSA values of < or =0.1. The most common hematologic toxicity was grade (3/4) neutropenia; grade 3 nonhematologic toxicities were rare, and no grade 4 nonhematologic toxicities were reported. Thus, the preliminary results suggest that docetaxel before hormonal therapy includes a PSA response in many prostate cancer patients with biochemical failure after definitive local therapies.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Docetaxel; Finasteride; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Recurrence, Local; Nitriles; Paclitaxel; Pilot Projects; Prostate-Specific Antigen; Prostatic Neoplasms; Salvage Therapy; Taxoids; Tosyl Compounds

A prospective randomized study was designed to determine whether flutamide (FLU) administered before treatment with a luteinizing hormone-releasing hormone agonist (LH-RHa) prevented prostate-specific antigen (PSA) flare in prostate cancer patients.. Prostate cancer patients were randomized into two groups and received either FLU (n = 11) or no pretreatment (n = 13) for 2 weeks before the initial injection of LH-RHa. LH-RHa (every 4 weeks) and FLU (every day) were administered throughout the period of this study. Blood samples, for the determination of PSA, testosterone (T), and luteinizing hormone levels, were collected before FLU administration, and before and 2, 7, 14, 28, 56, and 84 days after the first administration of LH-RHa.. Treatment with FLU prior to LH-RHa induced an early decline in PSA level. The mean PSA level showed no significant secondary rise after LH-RHa administration in those patients with FLU pretreatment. Patients in both groups showed T flare after the first LH-RHa administration. However, the number of patients with PSA flare was significantly lower in patients with prior FLU administration than in those with LH-RHa alone.. These results clearly demonstrate that, in patients with prostatic cancer, the administration of FLU for 2 weeks prior to the first LH-RHa administration is effective in preventing PSA flare, as well as in inducing an early decline in PSA levels.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Drug Administration Schedule; Flutamide; Goserelin; Humans; Injections, Subcutaneous; Leuprolide; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms

Prostate carcinoma therapy with combined androgen blockade may result in high bone-turnover with significant bone loss. This study was undertaken to evaluate the antiosteoporotic efficacy of intravenous pamidronate in a double blind, randomized, placebo-controlled, crossover study.. Twenty-one consecutive men with metastatic prostate carcinoma who were receiving combined androgen blockade with a long-acting gonadotropin-releasing hormone agonist (gosarelin acetate) and an androgen antagonist (flutamide or bicalutamide) were evaluated at baseline and at 6 and 12 months after therapy. They were randomly assigned to receive a single intravenous infusion of 500 mL of normal saline solution diluted with either pamidronate (90 mg) or placebo at baseline and with a crossover at 6 months. Lumbar-spine bone-mineral densities (BMDs) were measured by spinal quantitative computed tomography (QCT), femoral neck BMDs were measured by dual-energy X-ray absorptiometry (DXA), and markers of bone turnover were measured by noninvasive methods. Data on 10 men with localized prostate carcinoma who were treated with radiotherapy alone, over the same period, was collected for comparison studies.. The mean age of the men was 75.1 years +/- 1.6 years. One man withdrew from the study because of deteriorating health, and two died from metastatic disease within the first 6 months. Combined androgen blockade normalized serum prostate-specific antigen activities (from an initial mean value of 86.2 ng/mL +/- 10.1 ng/mL) and maintained serum free testosterone concentrations in the hypogonadal range (< 2.2 pmol/L) in all men throughout the study. Treatment with pamidronate resulted in a 7.8% +/- 1.5% increase in mean lumbar spine QCT from 79.4 mg/cm(3) (95% confidence interval [CI], 64-94 mg/cm(3)) to 85.6 mg/cm(3) (95% CI, 70-101 mg/cm(3)) (P = 0.0005) and a 2% +/- 0.9% increase in mean total femoral neck DXA from 0.98 g/cm(2) (95% CI, 0.90 -1.05 g/cm(2)) to 1.0 mg/cm(2) (95% CI, 0.91-1.08 g/cm(2)) (P = 0.02). Conversely, treatment with placebo, resulted in a 5.7% +/- 1.6% decrease in mean lumbar spine QCT and a 2.3% +/- 0.7% decrease in mean total femoral neck DXA (P = 0.0001 and P = 0.0007 for the comparison of percentage change between the pamidronate and placebo treatments). After pamidronate therapy, serum bone Gla-protein concentrations decreased by 16.8% +/- 5.9%, and urinary deoxypyridinoline excretion rates decreased by 18.5% +/- 12.8% (P < 0.01 respectively for the comparison between pamidronate and placebo treatment).. This study demonstrated that a single intravenous infusion of pamidronate (90 mg) significantly reduced the high bone turnover and bone loss (for at least 6 mos) in men with prostate carcinoma who had been rendered hypogonadal with combined androgen blockade therapy.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Bone Density; Cross-Over Studies; Diphosphonates; Double-Blind Method; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Injections, Intravenous; Male; Osteoporosis; Pamidronate; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

To assess the feasibility of administering a combination of suramin and hydrocortisone in addition to androgen deprivation in a cooperative group setting; to assess the feasibility of treatment with multiple courses of suramin; and to assess progression-free and overall survival in patients with newly diagnosed metastatic prostate cancer who underwent such treatment.. Patients with newly diagnosed metastatic prostate cancer who had adequate hematologic, hepatic, renal, neurologic, and coagulation parameters were treated by combined androgen deprivation and suramin plus hydrocortisone. Suramin was administered on a 78-day fixed dosing schedule (one cycle), and suramin treatment cycles were repeated every 6 months for a total of four cycles. The statistical design was developed on the basis of the feasibility of administering suramin, as judged by the number of patients who developed neurotoxicity of grade 3 or higher or by treatment interruption of 4 weeks or longer due to any persistent suramin-related toxicity.. Of the 62 patients enrolled onto the study between August 1994 and January 1997, 59 were eligible and assessable for toxicity on the first cycle. Thirty-two (54%) of 59 patients received a second cycle, 13 (22%) of 59 patients received a third cycle, and only five patients (8%) received a fourth cycle. During the first cycle, 27 patients were removed from the study: 17 because of toxicity, five because of disease progression, two who had died, and three because of other reasons. There was one therapy-related death. Grade 4 toxicities were noted in 11 and three patients during first and second courses, respectively. Neurotoxicity of grade 3 or higher was observed in nine and seven patients during the first and second cycles, respectively. Fifteen patients had treatment interruptions of 4 weeks or longer. Overall, only 54% (95% confidence interval, 41% to 67%) of the patients demonstrated acceptable limits of toxicity.. Suramin plus hydrocortisone and androgen deprivation has limited applicability in the treatment of patients with newly diagnosed metastatic prostate cancer.

Topics: Adult; Aged; Androgens; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Drug Administration Schedule; Feasibility Studies; Goserelin; Humans; Hydrocortisone; Leuprolide; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Suramin; Treatment Outcome

To explore whether less than 120 days of an antiandrogen plus a luteinizing hormone-releasing hormone agonist resulted in a different survival outcome than 120 days or more of combined treatment in patients with Stage D2 prostate cancer.. Survival data were available from a previously published controlled trial that had evaluated the efficacy and tolerability of two antiandrogens, bicalutamide and flutamide, each combined with a monthly depot preparation of leuprolide or goserelin, in 813 patients with Stage D2 prostate cancer. Cox's proportional hazards regression model assessed the relative effects of the length of combined androgen blockade (CAB) therapy on survival. This analysis was repeated in the subset of patients who lived at least 2 years beyond the date of randomization. Data were obtained at a median follow-up of 160 weeks.. A survival benefit was demonstrated for patients receiving prolonged CAB therapy, with a hazard ratio of 0.275 (95% confidence interval 0.213 to 0.355, P = 0.0001) in favor of patients who received 120 days or more of CAB therapy (median survival 1035 days versus 302 days for less than 120 days of therapy). This result was confirmed in the patients who lived at least 2 years, in whom the median survival time was increased by 35%. The hazard ratio for 120 days or more of CAB therapy versus less than 120 days was 0.415 (95% confidence interval 0.246 to 0.702, P = 0.001).. The results of the present exploratory analysis suggest that prolonged (120 days or more) antiandrogen treatment as part of CAB therapy may result in a better survival outcome.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Survival Rate; Tosyl Compounds

The aim of this study was to compare the effects of the nonsteroidal antiandrogen flutamide plus the LH-RH analogue goserelin acetate (combined androgen blockade [CAB]) with goserelin acetate alone in patients with advanced prostate cancer. The original analyses at 25 and 56 months of follow-up have been reported previously, and here we report the final survival analysis after 10 years of follow-up.. 589 patients with advanced prostate cancer (55% with metastatic [M1] and 45% with locally advanced [M0] disease) were randomized to receive goserelin acetate 3.6 mg either alone or in combination with flutamide (250 mg three times daily).. A total of 583 patients were included in the analysis. There was a small, but nonsignificant, benefit for CAB compared with goserelin acetate alone in all patients with respect to survival (hazard ratio 0.88, 95% CI 0.73, 1.06). Subgroup analysis of M0 and M1 patients showed similar results (M0: hazard ratio 0.92, 95% CI 0.68, 1.25; M1: hazard ratio 0.85, 95% CI 0.66, 1. 08). The treatment effect was not significantly different for M0 and M1 patients (p = 0.685).. In this large randomized trial containing significant numbers of M0 patients, after 10 years there was a small but nonsignificant benefit for CAB over castration alone.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Survival Rate

In 1997 the Trans-Tasman Radiation Oncology Group (TROG) performed a quality assurance (QA) audit of its phase III randomized clinical trial investigating the effectiveness of different durations of maximal androgen deprivation prior to and during definitive radiation therapy for locally advanced carcinoma of the prostate (TROG 96.01). The audit reviewed a total of 60 cases from 15 centres across Australia and New Zealand. In addition to verification of technical adherence to the protocol, the audit also incorporated a survey of centre planning techniques and a QA time/cost analysis. The present report builds on TROG's first technical audit conducted in 1996 for the phase III accelerated head and neck trial (TROG 91.01) and highlights the significant progress TROG has made in the interim period. The audit provides a strong validation of the results of the 96.01 trial, as well as valuable budgeting and treatment planning information for future trials. Overall improvements were detected in data quality and quantity, and in protocol compliance, with a reduction in the rate of unacceptable protocol violations from 10 to 4%. Audit design, staff education and increased data management resources were identified as the main contributing factors to these improvements. In addition, a budget estimate of $100 per patient has been proposed for conducting similar technical audits. The next major QA project to be undertaken by TROG during the period 1998-1999 is an intercentre dosimetry study. Trial funding and staff education have been targeted as the key major issues essential to the continued success and expansion of TROG's QA programme.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Costs and Cost Analysis; Flutamide; Goserelin; Humans; Male; Medical Audit; Prostatic Neoplasms; Quality Assurance, Health Care; Radiotherapy, Adjuvant; Time Factors

To evaluate changes of the volume of the cancerous prostatic gland during androgen deprivation (AD) started immediately after diagnosis (IAD). Hypothetically, these data would assist the radiotherapist to determine the appropriate duration of pre-radiotherapy downsizing neoadjuvant luteinizing hormone releasing hormone (LHRH) treatment. A second aim was to assess any increase of the prostatic volume during the 1st year of diagnosis in patients who were allocated to a deferred treatment policy (DAD). METHODS AND MATERIALS Thirteen patients in the IAD cohort and 13 patients in the DAD group, all with T1-3pN1-2M0 prostate cancer, had regular computed tomography/magnetic resonance (CT/MR) examinations during the 1st year after randomization within the EORTC-GU trial 30846. Pre-treatment prostate specific antigen (PSA) values were available in only 12 patients.. In the IAD group the prostate gland decreased with significant difference as compared with the DAD patients (P=0.033). As compared with the pre-treatment situation the prostate gland in the IAD group was reduced in size by 18, 35, and 46% at 1, 6, and 12 months, respectively. In four of six evaluable IAD patients the prostatic volume continued to shrink after achievement of the nadir PSA level (at 3 months). In three of the 13 DAD patients the prostate volume increased by >25% during the 1st 3 months after randomization.. If neoadjuvant androgen deprivation is applied before local treatment to downsize the volume of the cancerous prostate gland, our limited data suggest that such treatment should last at least 6 months in order to achieve a maximal effect in the majority of patients. In about 1/4 of untreated patients an increase in the prostate volume by >25% may occur within 3 months of diagnosis. If no AD is given, radiotherapy should start within this period.

Topics: Adult; Aged; Androgens; Antineoplastic Agents, Hormonal; Confidence Intervals; Drug Administration Schedule; Follow-Up Studies; Goserelin; Humans; Injections, Subcutaneous; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Probability; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Reference Values; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Neoadjuvant hormonal therapy (NHT) has been used for more than a decade for prostate cancer, but the results of clinical trials are only now becoming available, and the value of the treatment is not yet clear. The authors reviewed the results of the European randomized trials to increase our understanding of the role of this treatment.. We report the results of 402 patients with prostate cancer (220 clinical stage T(2) and 182 clinical T(3) tumor), of whom 192 were randomly assigned to NHT using an LHRH analog (goserelin) plus flutamide for a period of 3 months (NHT) and 210 underwent radical prostatectomy only (RP).. "Pathologic downstaging" occurred in 15% and 7% of the NHT and the RP group, respectively (P < 0.01). Fifty of the 189 patients in the NHT group (26%) and 68 of the 209 patients in the RP group (33%) developed disease progression, as determined by rising serum prostate specific antigen (PSA) concentration. Regarding local disease progression, the advantage for the use of NHT approached but did not reach statistical significance:18 of 189 patients (10%) in the NHT group and 33 of 209 patients (16%) in the RP group (P = 0. 07).. Although there was a trend in favor of the NHT group with respect to the number of patients with PSA progression and the number with local disease progression, it did not reach statistical significance. These results may be attributable to a true lack of benefit of adjuvant hormonal ablation or to a lack of statistical power to demonstrate a difference in a subset of patients who might benefit from this therapy.

Topics: Androgens; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Europe; Flutamide; Goserelin; Humans; Male; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

To evaluate the long-term effects of 3-month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer.. We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only.. 'Clinical downstaging' was seen in 30% of cases in the neoadjuvantly treated group (NEO). 'Pathological downstaging' occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41).. In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings.

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Disease-Free Survival; Europe; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Neoplasm Staging; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Time Factors

The first data analysis of the European Organization for Research and Treatment of Cancer (EORTC) 30853 trial indicated a significantly longer time to progression and duration of survival for the maximal androgen blockade (MAB) treatment arm. However, the MAB treatment arm had a higher frequency of reported side effects.. The quality-adjusted survival (Q-TWiST) method was applied to perform a secondary analysis of the EORTC 30853 trial in order to obtain a quality-adjusted survival (QAS) analysis. Two models with different definitions of the progression health state were used for the analysis. In the first model, progression was defined by both objective and subjective criteria, and in the second model only by increase in pain score. The approach was also extended to include an analysis using actual utility scores (Q-tility) of patients in the relevant health states.. Based on Q-tility scores obtained from a separate study of a cohort of prostate cancer patients, the QAS analysis resulted in a 5.2-month difference (95% CI, -1.1; 11.5 months) in favor of zoladex and flutamide, equal in magnitude to the benefit found in the unadjusted survival analysis.. A QAS analysis such as the Q-TWiST method may be preferred over the unadjusted approach in clinical trials where the health states are clearly distinct, and differ significantly in either duration or quality of life (QOL), or both. The second model, with progression defined as increase in pain score, made no difference to the results in this study because of the small difference in duration of the pain-progression health state between treatment arms. However, Q-tility scores from the separate cross-sectional study that was used in this Q-TWiST analysis showed that a subjective definition of health states better reflects differences in QOL between the health states that the patients experience during follow-up.

Topics: Antineoplastic Agents, Hormonal; Combined Modality Therapy; Flutamide; Goserelin; Humans; Male; Neoplasm Metastasis; Orchiectomy; Pain Measurement; Prostatic Neoplasms; Quality of Life; Quality-Adjusted Life Years; Survival Analysis

To determine the hormonal (luteinizing hormone [LH] and testosterone) and biochemical (serum prostate-specific antigen [PSA]) response to withdrawal of luteinizing hormone-releasing hormone (LHRH) agonists in patients who received more than 2 years of LHRH therapy for advanced prostate cancer.. Fourteen patients with clinical Stage T3 or higher prostate cancer and no evidence of clinical or biochemical progression, who had received 2 years or more of LHRH therapy, were enrolled at the time of their scheduled 3-month depot injection. Patients underwent history, physical examination, and measurement of serum PSA, LH, and testosterone at baseline, monthly for 3 months, and then every 3 months for 1 year following LHRH withdrawal.. The mean age of patients was 70.3 years (range 56 to 84). Patients previously received LHRH agonist for a mean of 38.6 months (range 25 to 82). All patients had castrate levels of testosterone (median 10.0 ng/dL) and suppressed LH levels (median 0.1 mIU/mL) at baseline. Median baseline PSA was 0.15 ng/mL. On multiple groupwise comparison, there was no significant change (compared with baseline) in LH or testosterone until 6 months after withdrawal and no change in PSA throughout the duration of the study (median PSA at 1 2 months 0.30 ng/mL). Despite significant increases in LH and testosterone when compared with baseline beginning at 6 months, both LH and testosterone remained markedly suppressed, with median testosterone remaining in the castrate range at both 6 and 9 months and significantly below the lower limit of normal at 12 months (median 111.0 ng/dL). Despite no statistically significant change for the entire cohort in serum PSA, a rising PSA was noted in 4 patients between 3 and 9 months, and LHRH therapy was reinitiated. The remaining patients continued to have suppressed LH and testosterone, with 4 patients remaining in the castrate range at 12 months.. The recovery of function of the hypothalamic-pituitary-testicular axis after prolonged LHRH administration is variable. Castrate levels of testosterone and suppressed LH may persist even up to 1 year after discontinuing LHRH. These results have significant implications regarding the interpretation of clinical trials incorporating neoadjuvant and adjuvant hormonal therapy. Further studies are needed to expand on these preliminary observations and should also address the feasibility of incorporating LHRH withdrawal into clinical practice.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Pilot Projects; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

The likelihood of finding organ-confined untreated prostate cancer (PCa) by pathological examination at the time of radical prostatectomy (RP) is only 50% in patients with clinically organ-confined disease. In addition, tumour is present at the resection margin in approximately 30% of clinical T2 (clinical stage B) cases. The issue of clinical "understaging" and of resection limit positivity have led to the development of novel management practices, including "neoadjuvant" hormonal therapy (NHT). The optimal duration of NHT is unknown. We undertook the present analysis to evaluate the effect of NHT on pathologic stage of PCa and resection limit status in patients with prostate cancer and treated with total androgen ablation either for three or six months before RP. Between January 1996 and February 1998, 259 men with prostate cancer underwent radical retropubic prostatectomy and bilateral pelvic node dissection in the 26 centres participating in the Italian randomised prospective PROSIT study. Whole mount sectioning of the complete RP specimens was adopted in each centre for accurately evaluating the pathologic stage and resection limit status. By February 1998, haematoxylin and eosin stained sections from 155 RP specimens had been received and evaluated by the reviewing pathologist (RM). 64 cases had not been treated with total androgen ablation (e.g. NHT) before RP was performed, whereas 58 and 33 had been treated for three and six months, respectively. 114 patients were clinical stage B whereas 41 were clinical stage C. After three months of total androgen ablation, pathological stage B was more prevalent among patients with clinical B tumours, compared with untreated patients (57% in treated patients vs. 36% in untreated). The percentage of cancers with negative margins was statistically significantly greater in patients treated with neoadjuvant therapy than those treated with immediate surgery alone (69% vs. 42%, respectively). After six months of NHT therapy the proportion of patients with pathological stage B (67% vs. 36%, respectively) and negative margins was greater than after 3 months (92% vs. 42%, respectively). For clinical C tumours, the prevalence of pathological stage B and negative margins in the patients treated for either 3 or 6 months was not as high as in the clinical B tumours, when compared with the untreated group (pathological stage B: 31% and 33% vs. 6% in the clinical C cases, respectively. Negative margins: 56% and 67% vs. 31%,

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nitriles; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Time Factors; Tosyl Compounds; Treatment Outcome

To determine the endocrine effects, efficacy and tolerability of a 10.8-mg depot formulation of Zoladextrade mark (goserelin acetate, Zeneca Pharmaceuticals, Wilmington, Delaware, USA), a luteinizing hormone-releasing hormone agonist analogue, when administration was extended from every 12 weeks to every 13 weeks in patients with advanced prostate cancer.. Between July 1995 and May 1996, 59 patients with either locally advanced (T3 or T4) or metastatic prostate cancer were enrolled in an open-label, multicentre trial. Primary efficacy endpoints were testosterone measurements, and assessments of prostate specific antigen (PSA) response, subjective and objective response. Quality of life (QoL) was a secondary efficacy endpoint.. Mean testosterone concentrations decreased to < 0.3 microgram/L by week 4 and remained so for the duration of treatment. There were no statistically significant differences in mean testosterone levels between weeks 12 and 13, or weeks 25 and 26. Serum testosterone suppression was adequate in all 58 evaluable patients at week 13, and 51 of 52 (98%) patients at week 26. Of the 58 evaluable patients, 52 (90%) had a PSA response. A subjective response was recorded for six of 11 evaluable patients. Of 58 patients evaluable for objective response, 46 (79%) had a partial response, three (5%) had stable disease and nine (16%) had objective progression. Except for a significant (P=0.014) decrease in overall sexual interest, QoL was unchanged during therapy. The most common side-effects, regardless of causality, were hot flushes (67%), pain (31%) and pelvic pain (22%). Mild injection-site complaints occurred with only three of 221 (1.4%) depot injections.. Zoladextrade mark 10.8-mg depot, administered every 13 weeks to patients with advanced prostatic cancer, is well tolerated, provides adequate suppression of serum testosterone and produces PSA, subjective and objective responses.

Topics: Aged; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Drug Administration Schedule; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Testosterone; Treatment Outcome

It was very reasonable to consider that the combination of the 5alpha-reductase, finasteride, and a pure antiandrogen such as flutamide should provide an effective form of maximal androgen blockade (MAB). Finasteride decreases intraprostatic levels of 5alpha-dihydrotestosterone (DHT), and the antiandrogen would restrain the biological action of the residual DHT by interfering with its association with androgen receptor. This form of MAB should sustain the concentration of testosterone in plasma, thereby maintaining sexual function and reasonable quality of life. In order to investigate this, a randomized multicenter phase II clinical trial of patients with untreated M1 cancer of the prostate was developed and undertaken.. Patients were randomly allocated to one of three treatment schedules: 1) goserelin, 3.6 mg, s.c., monthly in combination with flutamide, 250 mg., t.i.d. and a placebo, daily, in the image of 2 x 5 mg finasteride; 2) goserelin, 3.6 mg., s.c., monthly in combination with finasteride, 10 mg (2 x 5 mg, daily) and a placebo (t.i.d.) in the image of flutamide; and 3) finasteride, 10 mg (2 x 5 mg, daily) in combination with flutamide (250 mg, t.i.d.). The reduction in concentration of serum PSA at 24 weeks was the endpoint of interest.. Baseline prostate-specific antigen (PSA) levels of the patients in the three groups were very similar. There was a substantial decrease in levels of PSA in the three groups prior to the end of the study, the percent decrease in the groups being: 1) goserelin and flutamide combination, 99.1% (95% Confidence interval (CI), 97.7, 99.6); 2) goserelin and finasteride combination, 98.75% (95% CI, 97.1, 99.5); and 3) finasteride and flutamide combination, 97.6%, 95% CI, 94.5, 98.9). In the Generalized linear model (GLM) analysis, there was no center by treatment group interaction (P = 20), and there were no significant differences between centers (P = 0.059) nor among the three treatment groups (P = 0.16).. The decrease in levels of PSA in such a group of patients with M1 cancer of the prostate over a 24-week period was surprisingly large, and the differences in these decreased levels between the three treatment arms were remarkably small. There were no apparent differences in bone scan scores, World Health Organization (WHO) performance status, and pain scores between the arms. With regard to sexual function associated with quality of life, there were the understandable difficulties of data collection from patients treated with goserelin.

Topics: 5-alpha Reductase Inhibitors; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Dihydrotestosterone; Enzyme Inhibitors; Finasteride; Flutamide; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms

Black race has been associated with a significantly increased risk of prostate cancer mortality. This exploratory analysis investigated the effect of race on the clinical outcome of combined androgen blockade (CAB).. Data for analysis were obtained from a double-blind, randomized, multicenter trial comparing CAB in the form of bicalutamide (50 mg once daily) or flutamide (250 mg three times daily) plus luteinizing hormone-releasing hormone analogs (LHRHa; goserelin acetate 3.6 mg, or leuprolide acetate 7.5 mg) in 813 patients with stage D(2) prostate cancer (median follow-up, 160 weeks). Patients were analyzed according to race (African American [AA], white, or other). The primary clinical events were disease progression and survival.. Four hundred and four patients received bicalutamide/LHRHa and 409 received flutamide/LHRHa. Although treatment with bicalutamide/LHRHa resulted in slightly longer time to progression and survival time in white and AA males than treatment with flutamide/LHRHa, the differences between the treatment groups were not statistically significant.. No marked effect of race on clinical outcome was observed regardless of antiandrogen, suggesting that similar treatment benefits are to be expected in either race.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Black People; Bone Neoplasms; Cohort Studies; Disease Progression; Disease-Free Survival; Double-Blind Method; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Tosyl Compounds; White People

To evaluate the effect of immediate androgen suppression in conjunction with standard external beam irradiation (RT) versus RT alone on a group of men after prostatectomy who had indications for adjuvant treatment.. A national prospective randomized trial (Radiation Therapy Oncology Group [RTOG] 85-31) comparing standard external beam RT plus immediate androgen suppression versus external beam RT alone with delayed hormonal treatment at relapse was initiated for patients with locally advanced adenocarcinoma of the prostate. One hundred thirty-nine of the patients in this trial had indications for adjuvant treatment after prostatectomy (eg, capsular penetration, seminal vesicle involvement). Seventy-one of the patients received RT with immediate androgen suppression (luteinizing hormone-releasing hormone [LHRH] agonist); 68 patients received RT alone with hormonal manipulation instituted only at the time of relapse.. With a median follow-up of 5 years, the estimated progression-free survival rate (failure defined as prostate-specific antigen [PSA] greater than 0.5 ng/mL) was 65% for the men who received combination therapy and 42% for those treated by RT alone with hormones reserved for relapse (P = 0.002). Differences in the rates of freedom from biochemical relapse were observed when failure was defined as PSA of 1.0 to 3.9 ng/mL (71% versus 46%; P = 0.008) and PSA greater than 4.0 ng/mL (76% versus 55%; P = 0.05), respectively. No differences were observed between the groups with respect to the end points of local control, distant failure, and overall survival. The use of immediate androgen suppression (ie, LHRH agonists) and the absence of pathologic nodal involvement were independently associated with prolongation of freedom from biochemical relapse by multivariate analysis.. Patients with prostate cancer and indications for postoperative RT should be considered for combined RT and hormonal manipulation. Because statistically significant advantages for this experimental approach could not be defined for all end points studied (in particular, overall survival), efforts should be made to enroll these patients in the recently activated RTOG trial (96-01) comparing RT plus placebo to the combination of RT plus Casodex in the postoperative setting.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Disease-Free Survival; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms

To compare the efficacy of bicalutamide monotherapy to maximal androgen blockade (MAB) in the treatment of advanced prostatic cancer.. Previously untreated patients with histologically proven stage C or D disease (American Urological Association Staging System) were randomly allocated to receive either bicalutamide or MAB. After disease progression, patients treated with bicalutamide were assigned to castration. The primary end point for this trial was overall survival. Secondary end points included response to treatment, disease progression, treatment safety, quality-of-life (QOL), and sexual function.. A total of 108 patients received bicalutamide and 112 received MAB. There was no difference in the percentage of patients whose prostate-specific antigen returned to normal levels. At the time of the present analysis (median follow-up time, 38 months; range, 1 to 60 months), 129 patients progressed and 89 died. There was no difference in the duration of either progression-free survival or overall survival. However, a survival trend favored bicalutamide in stage C disease but MAB in stage D disease. Overall and subgroup trends were confirmed by multivariate analysis. Serious adverse events and treatment discontinuations were more common in patients receiving MAB (P =.08 and P =.04, respectively). Fewer patients in the bicalutamide group complained of loss of libido (P =. 01) and of erectile dysfunction (P =.002). Significant trends favored bicalutamide-treated patients also with respect to their QOL, namely relative to social functioning, vitality, emotional well-being, and physical capacity.. Bicalutamide monotherapy yielded comparable results relative to standard treatment with MAB, induced fewer side effects, and produced a better QOL.

Topics: Adult; Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Consumer Product Safety; Disease Progression; Disease-Free Survival; Erectile Dysfunction; Flutamide; Goserelin; Humans; Italy; Male; Middle Aged; Nitriles; Proportional Hazards Models; Prostatic Neoplasms; Quality of Life; Survival Rate; Tosyl Compounds

Because the optimal timing of the institution of antiandrogen therapy for prostate cancer is controversial, we compared immediate and delayed treatment in patients who had minimal residual disease after radical prostatectomy.. Ninety-eight men who underwent radical prostatectomy and pelvic lymphadenectomy and who were found to have nodal metastases were randomly assigned to receive immediate antiandrogen therapy, with either goserelin, a synthetic agonist of gonadotropin-releasing hormone, or bilateral orchiectomy, or to be followed until disease progression. The patients were assessed quarterly during the first year and then semiannually.. After a median of 7.1 years of follow-up, 7 of 47 men who received immediate antiandrogen treatment had died, as compared with 18 of 51 men in the observation group (P=0.02). The cause of death was prostate cancer in 3 men in the immediate-treatment group and in 16 men in the observation group (P<0.01). At the time of the last follow-up, 36 men in the immediate-treatment group (77 percent) and 9 men in the observation group (18 percent) were alive and had no evidence of recurrent disease, including undetectable serum prostate-specific antigen levels (P<0.001). In the observation group, the disease recurred in 42 men; 13 of the 36 who were treated had a complete response to local treatment or hormonal therapy (or both), 16 died of prostate cancer, and 1 died of another disease. The remaining men in this group were alive with progressive disease at the time of the last follow-up or had had a recent relapse. Except for the treatment group (immediate therapy or observation), no clinical or histologic characteristic significantly influenced the outcome.. Immediate antiandrogen therapy after radical prostatectomy and pelvic lymphadenectomy improves survival and reduces the risk of recurrence in patients with node-positive prostate cancer.

Topics: Aged; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Disease Progression; Follow-Up Studies; Goserelin; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Orchiectomy; Prostatectomy; Prostatic Neoplasms; Survival Analysis; Time Factors

The aims of this randomized, controlled study were to investigate the efficacy and safety of long-term monotherapy with the luteinizing hormone-releasing hormone agonist goserelin acetate compared with both short- and long-term combined androgen blockade.. Patients with advanced prostate cancer (n = 371) were randomized to treatment with goserelin acetate alone or a combination of goserelin acetate plus either long-term or short-term antiandrogen (chlormadinone acetate) or short-term estrogen (diethylstilbestrol diphosphate).. There were no significant differences between the treatment groups with respect to objective progression, overall survival or disease-specific survival. Nevertheless, subgroup analysis suggested that patients with minimal disease or a good prognosis might benefit more from combined androgen blockade than other patients. Combined androgen blockade significantly reduced the incidence of disease flare compared with goserelin acetate treatment alone.. Neither short- nor long-term combined androgen blockade had a survival advantage over goserelin acetate alone.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chlormadinone Acetate; Diethylstilbestrol; Disease-Free Survival; Drug Administration Schedule; Drug Therapy, Combination; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Survival Rate

To compare the efficacy, tolerability, and quality of life benefits of bicalutamide (Casodex) 150-mg/day monotherapy and castration in previously untreated nonmetastatic (M0) advanced prostate cancer.. A total of 480 patients with Stage T3/T4 nonmetastatic disease randomly received oral bicalutamide 150 mg/day or castration (either bilateral orchiectomy or goserelin acetate [Zoladex] 3.6 mg every 28 days) in a 2:1 ratio in two open multicenter studies (studies 306 and 307). The design of these studies was similar to allow a pooled analysis.. In the combined survival analysis, at median follow-up of 202 and 205 weeks in studies 306 and 307, respectively, with 31% of the cases resulting in death, bicalutamide 150-mg monotherapy was statistically equivalent to castration; the risk of death from any cause was 7% less with bicalutamide than with castration (hazard ratio [HR] = 0.93). Data on time to treatment failure and objective progression could not be pooled, as results for these end points differed between the trials. In study 306, bicalutamide 150-mg monotherapy increased time to objective progression (HR = 0.58; P = 0.033) and treatment failure (HR = 0.66; P = 0.074), whereas in study 307, time to progression (HR = 1.35; P = 0.0471) and treatment failure (HR = 1.24; P = 0.097) favored castration. Bicalutamide therapy showed significant advantages over castration for both sexual interest (P = 0.029) and physical capacity (P = 0.046). Bicalutamide 150-mg monotherapy was well tolerated.. Bicalutamide 150-mg monotherapy provides a similar survival outcome to castration in previously untreated patients with nonmetastatic advanced prostate cancer and confers statistically significant benefits over castration with respect to sexual interest and physical capacity.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Castration; Disease Progression; Double-Blind Method; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Quality of Life; Survival Rate; Time Factors; Tosyl Compounds

The EORTC conducted two randomized phase III trials of maximal androgen blockade (MAB) in 695 patients with metastatic prostate cancer. Trial 30,843 compared orchidectomy or buserelin to buserelin plus cyproterone acetate and showed no significant difference in survival while trial 30,853 showed that Zoladex plus flutamide had a significantly longer survival than orchidectomy. Reasons for this discrepancy were sought.. In order to determine whether differences in patient characteristics could explain these possibly contradictory results, a Cox proportional hazards regression model was used to identify prognostic factors for survival in each study. Patients were divided into risk groups (good or poor prognosis with 3.5 and 1.75 years' median survival, respectively) based on their alkaline phosphatase, hemoglobin, performance status, pain score, T category and G grade at entry on study.. The survival advantage of MAB in 30,853 was limited to patients with a good prognosis (164/302 (54%) of the patients). In 30,843, only 93/337 patients (28%) had a good prognosis so there were insufficient data to draw separate conclusions in these patients. Despite the limitations of subgroup analyses, these results show that patients in 30,843 had on the average a worse prognosis than patients in 30,853. Hence there were fewer good prognosis patients who could potentially benefit from MAB, thus providing one possible explanation for the overall negative conclusion.. These studies once again underline the importance of taking into account patient characteristics when designing and interpreting metastatic prostate cancer trials. They also provide criteria which may be used to define risk groups as part of a protocol's patient eligibility criteria. In the design of future trials assessing MAB, a sufficient number of good prognosis patients should be entered to reliably assess treatment efficacy in this subgroup.

Topics: Aged; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Combined Modality Therapy; Cyproterone Acetate; Disease-Free Survival; Flutamide; Goserelin; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Orchiectomy; Prognosis; Proportional Hazards Models; Prostatic Neoplasms; Risk Assessment; Survival Rate

This prospective, randomized phase III study was initiated to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist depot formulation, goserelin acetate (3.6 mg s.c. once every 4 weeks) and flutamide (250 mg 3 x daily) in patients with metastatic prostate cancer.. Relative treatment efficacy was assessed by comparing the two treatment groups with respect to response, time to first progression, progression-free survival, duration of survival and time to death due to malignant disease.. There was a difference in response only with respect to a more frequent decrease to normal of the serum prostate acid phosphatase in patients assigned to maximal androgen blockade treatment. Additionally, maximal androgen blockade treatment showed significantly better results for duration of survival (p = 0.04), time to death due to malignant disease (p = 0.008), time to first progression (p = 0.009) and progression-free survival (p = 0.02). The most frequent side effects for both treatments included hot flushes and gynaecomastia.. Increased time to progression and duration of survival is achieved by the combination of flutamide and goserelin when compared to bilateral orchiectomy.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma; Disease Progression; Disease-Free Survival; Flutamide; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prognosis; Prospective Studies; Prostatic Neoplasms; Survival Rate; Treatment Outcome

To perform exploratory analyses of data from a controlled trial that assessed the efficacy and tolerability of two antiandrogens, bicalutamide and flutamide, each combined with monthly depot preparations of leuprolide or goserelin, in patients with Stage D2 prostate cancer. One analysis compared goserelin plus antiandrogen therapy with leuprolide plus antiandrogen therapy; a second analysis compared the four combined androgen blockade (CAB) regimens.. This was a randomized, multicenter trial, open-label for luteinizing hormone releasing hormone analogue (LHRH-A) therapy, double-blind for antiandrogen therapy, with a two-by-two factorial design. Eight-hundred thirteen patients were allocated in a ratio of 2:1 to goserelin therapy (3.6 mg every 28 days) or leuprolide therapy (7.5 mg every 28 days) and 1:1 to bicalutamide therapy (50 mg once a day) or flutamide therapy (250 mg three times a day). The end points of time to progression and survival were assessed with a median of 160 weeks of follow-up.. The percentages of progression events (70.9% versus 73.3%) and deaths (54.3% versus 56.8%) were similar for goserelin plus antiandrogen and leuprolide plus antiandrogen therapies. The hazard ratios for goserelin plus antiandrogen therapy to leuprolide plus antiandrogen therapy were 0.99 (95% confidence interval [CI] 0.84 to 1.18; P = 0.92) and 0.91 (95% CI 0.75 to 1.11; P = 0.34) for time to progression and survival, respectively. Goserelin plus antiandrogen and leuprolide plus antiandrogen therapies were generally well tolerated, and the side effects associated with depot administration occurred with a low frequency in the two groups. There were no significant differences among the goserelin plus bicalutamide, goserelin plus flutamide, or leuprolide plus bicalutamide therapy groups, but leuprolide plus flutamide therapy had a significantly poorer outcome than the other three therapies. The side-effect profiles for the four CAB groups were generally similar; diarrhea was more common among patients treated with flutamide and hematuria was more common among patients treated with bicalutamide.. Although the results of these exploratory analyses should be interpreted with caution, they indicate that goserelin plus antiandrogen and leuprolide plus antiandrogen therapies are similarly well tolerated and have equivalent time to progression and survival, and that leuprolide plus flutamide therapy appears to be the least effective of the four CAB regimens.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Double-Blind Method; Flutamide; Goserelin; Humans; Leuprolide; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Survival Rate; Tosyl Compounds

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Goserelin; Humans; Lymphatic Irradiation; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Treatment Outcome

Although androgen suppression results in a tumor response/remission in the majority of patients with carcinoma of the prostate, its potential value as an adjuvant has not been substantiated.. In 1987, the Radiation Therapy Oncology Group (RTOG) initiated a randomized phase III trial of adjuvant goserelin in definitively irradiated patients with carcinoma of the prostate. A total of 977 patients had been accessioned to the study. Of these, 945 remained analyzable: 477 on the adjuvant arm and 468 on the observation arm.. Actuarial projections show that at 5 years, 84% of patients on the adjuvant goserelin arm and 71% on the observation arm remain without evidence of local recurrence (P < .0001). The corresponding figures for freedom from distant metastases and disease-free survival are 83% versus 70% (P < .001) and 60% and 44% (P < .0001). If prostate-specific antigen (PSA) level greater than 1.5 ng is included as a failure (after > or = 1 year), the 5-year disease-free survival rate on the adjuvant goserelin arm is 53% versus 20% on the observation arm (P < .0001). The 5-year survival rate (for the entire population) is 75% on the adjuvant arm versus 71% on the observation arm (P = .52). However, in patients with centrally reviewed tumors with a Gleason score of 8 to 10, the difference in actuarial 5-year survival (66% on the adjuvant goserelin arm v 55% on the observation arm) reaches statistical significance (P = .03).. Application of androgen suppression as an adjuvant to definitive radiotherapy has been associated with a highly significant improvement in local control and freedom from disease progression. At this point, with a median follow-up time of 4.5 years, a significant improvement in survival has been observed only in patients with centrally reviewed tumors with a Gleason score of 8 to 10.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Follow-Up Studies; Goserelin; Humans; Male; Prognosis; Prostatic Neoplasms; Survival Analysis

To assess the pathological staging and biochemical progression-free survival (assessed using serum prostate-specific antigen level) of patients with clinically localized prostate cancer using neoadjuvant androgen deprivation therapy (ADT) in combination with radical retropubic prostatectomy (RRP).. A prospective study was carried out on 69 patients with localized prostate cancer who were enrolled in a trial of 3 months of ADT followed by RRP (group 1). These patients were compared with 72 patients matched for age and clinical stage who declined ADT therapy and had RRP concurrently (group 2). Assignment to the individual treatment groups was thus determined by the patient's preference and not the physician's selection. Pathological staging and biochemical progression-free recurrence were compared between the groups.. The rate of organ-confined (pT2) tumours was 74% in group 1 and 49% in group 2 (P < 0.01), and the rate of margin-negative tumours was 87% in group 1 and 64% in group 2 (P < 0.01). Within a median follow-up of 35 months, there was no significant difference in biochemical failure between the groups (P = 0.37). Patients with pT2 disease, regardless of treatment, had similar biochemical failure rates. In the patients with margin-positive disease, there was a significantly higher biochemical failure rate in group 1 (P = 0.02).. The rates of organ- and specimen-confined disease were higher among the patients treated with ADT. The preliminary follow-up suggested that patients with pT2 disease after ADT have a biochemical progression-free recurrence rate similar to pT2 patients treated with RRP alone. Additionally, high biochemical failure rates in patients with margin-positive disease after ADT may identify a subset of more biologically aggressive tumours in need of early adjuvant treatment.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Flutamide; Goserelin; Humans; Lymph Node Excision; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Treatment Outcome

The use of neoadjuvant chemotherapy prior to definitive surgery has been firmly established in other areas of oncology, most notably in the treatment to testis and Wilm's tumors. The use of neoadjuvant androgen deprivation therapy (ADT) in conjunction with radical prostatectomy remains a source of controversy. We have conducted phase II and phase III studies to assess the effects of 3 months of preoperative ADT (goserelin and flutamide) on the pathologic staging and postsurgery prostate-specific antigen (PSA) relapse rate. We also reviewed the data confirming the understaging of clinically localized prostatic cancer and the experimental data providing the conceptual support for ADT.. We report the results of 141 patients, Stage T0-T0, in a Phase II study with concurrent, nonrandomized controls (N = 72) versus a treatment arm (N = 69) of men receiving 3 months of ADT with 3.6 mg goserelin for 28 days and 750 mg flutamide daily. We also report the interim results in 114 men participating in a prospective, randomized study of ADT versus surgery alone.. The 69 patients who received 3 months of goserelin and flutamide followed by radical prostatectomy had a pathologic organ-confined cancer rate of 74%, versus 48% in the control group who received no ADT prior to surgery. The margin-positive rate was 10% in the ADT group versus 33% in the control group. In an interim analysis of 114 patients (59 ADT, 55 control), the organ-confined and margin-positive rates were 73% and 17% in the ADT group versus 56% and 36% in the control arm, respectively. The PSA disease-free rate at a mean follow-up of 28.6 months (range 6.2 to 49.5 months) was 89% in the ADT-treated patients (N = 98) and 84% in the control patients (N = 96). There was no statistical difference demonstrated between the arms with respect to biochemical failure.. While the pathologic staging of tumors following ADT treatment was improved compared with surgical controls, to date the PSA disease-free survival rates are similar. Patients with residual extracapsular (P3) disease after ADT manifest an increased PSA failure rate compared with those with P3 tumors treated by surgery alone. This suggests that ADT may identify a subset of patients with aggressive tumors that may be candidates for additional therapeutic interventions even before PSA failure occurs.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Neoplastic Cells, Circulating; Preoperative Care; Prostatic Neoplasms

To evaluate the short- and long-term effects of neoadjuvant hormonal treatment in locally confined prostate cancer.. We report the preliminary results of 354 patients (199 with a clinical T2 tumor and 155 with a clinical T3 tumor) of whom 164 randomly received neoadjuvant total androgen deprivation using a luteinizing-hormone-releasing hormone (LHRH) analog (goserelin) plus flutamide for a period of 3 months.. Serum prostate-specific antigen (PSA) levels and prostatic volume decreased from a mean of 19.9 ng/mL and 37.7 cm3 to a mean of 0.8 ng/mL and 26.5 cm3 after 3 months of neoadjuvant therapy. "Clinical down-staging" was seen in 32% in the neoadjuvantly treated group. "Pathological downstaging" percentages were 6% and 16% in the direct radical prostatectomy group and neoadjuvantly-treated group, respectively (P < 0.01). In patients with clinical T2 tumors, a significant difference in number of positive margins was shown in favor of the neoadjuvantly treated group (P < 0.01). In patients with clinical T3 tumors, a significant difference could not be detected (P = 0.14). In 215 patients with a mean follow-up time of 15 months, the calculated 95% confidence intervals of mean time of PSA progression-free survival were 26 to 35 months in the neoadjuvantly-treated group and 28 to 37 months in the direct radical prostatectomy group, indicating no significant differences between treatment groups. However, follow-up time is currently too short to draw definite conclusions.. These early data confirm high understaging percentages in clinical staging. The clinical relevance of the statistically significant smaller numbers of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor will have to be confirmed when further follow-up allows an accurate evaluation of time to PSA progression, local recurrence, and distant metastases. Presently, neoadjuvant therapy is not advisable outside clinical research settings.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Flutamide; Goserelin; Humans; Male; Neoplasm Staging; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Time Factors

The present study evaluated serial serum measurements of tissue polypeptide-specific antigen (TPS) in comparison with prostate-specific antigen (PSA) for assessment of tumour progression in patients with advanced prostate cancer receiving intermittent androgen suppression therapy (IAS). Twenty-three men were recruited into an IAS trial consisting of an initial 8 months of androgen suppression, followed by cycles of treatment cessation and resumption of therapy upon increases of PSA > 20 ng ml(-1) to prolong the hormone responsiveness of the tumour cells. Periods of androgen suppression resulted in reversible reduction in serum testosterone (< 1.8 nmol I(-1)) and PSA (< 4 ng ml(-1)) and decreases in tumour volume (mean reduction for first cycle 24 +/- 10%), indicating partial growth arrest and apoptotic regression of the tumours. In contrast to PSA values, non-specifically elevated TPS values were found in 8 of 23 patients. In 15 of 23 patients, TPS fell during periods of apoptotic tumour regression and increased simultaneously with testosterone and preceded the increases in PSA by 2 months during the period of treatment cessation. Although TPS represents a highly sensitive marker of tumour proliferation in this IAS clinical model of controlled tumour regression and regrowth, its low specificity compared with PSA limits its usefulness to monitoring of prostate cancer patients with proven absence of non-specific elevations of this marker.

Topics: Adenocarcinoma; Androgen Antagonists; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cyproterone Acetate; Drug Administration Schedule; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Tissue Polypeptide Antigen

We conducted a randomized, prospective trial comparing external irradiation with external irradiation plus goserelin (an agonist analogue of gonadotropin-releasing hormone that reduces testosterone secretion) in patients with locally advanced prostate cancer.. From 1987 to 1995, 415 patients with locally advanced prostate cancer were randomly assigned to receive radiotherapy alone or radiotherapy plus immediate treatment with goserelin. The patients had a median age of 71 years (range, 51 to 80). Patients in both groups received 50 Gy of radiation to the pelvis over a period of five weeks and an additional 20 Gy over an additional two weeks as a prostatic boost. Patients in the combined-treatment group received 3.6 mg of goserelin (Zoladex) subcutaneously every four weeks starting on the first day of irradiation and continuing for three years; those patients also received cyproterone acetate (150 mg orally per day) during the first month of treatment to inhibit the transient rise in testosterone associated with the administration of goserelin.. Data were available for analysis on 401 patients. The median follow-up was 45 months. Kaplan-Meier estimates of overall survival at five years were 79 percent (95 percent confidence interval, 72 to 86 percent) in the combined-treatment group and 62 percent (95 percent confidence interval, 52 to 72 percent) in the radiotherapy group (P=0.001). The proportion of surviving patients who were free of disease at five years was 85 percent (95 percent confidence interval, 78 to 92 percent) in the combined-treatment group and 48 percent (95 percent confidence interval, 38 to 58 percent) in the radiotherapy group (P<0.001).. Adjuvant treatment with goserelin, when started simultaneously with external irradiation, improves local control and survival in patients with locally advanced prostate cancer.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Cyproterone Acetate; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Survival Analysis; Treatment Outcome

To compare the efficacy and tolerability of bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with metastatic (Stage D2) prostate cancer.. This was a randomized, double-blind (for antiandrogen therapy), multicenter study with a two-by-two factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days).. The median times to progression and death were 97 and 180 weeks for the bicalutamide plus LHRH-A group compared with 77 and 148 weeks for the flutamide plus LHRH-A group. The hazard ratio for time to progression for bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.93 (95% confidence interval [CI] 0.79 to 1.10, P = 0.41) and that for survival time was 0.87 (95% CI 0.72 to 1.05, P = 0.15). The therapies were generally well tolerated. The most common adverse event in the two groups was hot flashes. The incidence of hematuria was significantly higher for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group (12% versus 6%, P = 0.007), but no patient withdrew from therapy because of hematuria. There was a significantly (26% versus 12%, P < 0.001) higher incidence of diarrhea and more withdrawals for diarrhea (25 patients versus 2) for the flutamide plus LHRH-A group relative to the bicalutamide plus LHRH-A group.. With a median follow-up time of 160 weeks, the combination of bicalutamide plus LHRH-A was well tolerated and had equivalent time to progression and survival compared with flutamide plus LHRH-A. Treatment with bicalutamide plus LHRH-A resulted in longer median survival than treatment with flutamide plus LHRH-A.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Flutamide; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Survival Rate; Tosyl Compounds

To review the outcome of therapy with maximal androgen blockade and compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer.. Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days).. At the time of analysis (median follow-up, 49 weeks), bicalutamide plus LHRH-A was associated with a statistically significant improvement in time-to-treatment failure, the primary endpoint, when compared with flutamide plus LHRH-A. The results with longer follow-up (median, 95 weeks) support previous findings of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however, the difference between groups was not statistically significant. A treatment failure endpoint was reached by 68% of patients in the bicalutamide plus LHRH-A group, compared with 72% of patients in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95% confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95% confidence limit for survival was 1.00, meeting the definition for equivalence (< 1.25). With longer follow-up, overall mortality was 34%, with equivalent survival between groups: 32% of patients in the bicalutamide plus LHRH-A group died, compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P = 0.29). The upper one-sided 95% confidence limit for survival was 1.07, meeting the definition for equivalence (< 1.25). Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001).. In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its efficacy and tolerability profile, together with its convenient once-daily dosing formulation, bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Flutamide; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Metastasis; Nitriles; Prostatic Neoplasms; Tosyl Compounds

To assess the pharmacodynamic equivalence of the new 10.8 mg. goserelin depot with the current 3.6 mg. depot 3 studies were performed in patients with advanced prostate cancer.. In 2 comparative studies 160 patients were randomized for dosing every 12 weeks using the 10.8 mg. depot or every 4 weeks using the 3.6 mg. depot. In the noncomparative study 35 patients received the 10.8 mg. depot. Blood sampling for serum testosterone and evaluation of toxicity was done during the 48-week study period.. Serum testosterone profiles of the 10.8 and 3.6 mg. goserlin depots were similar with testosterone levels decreasing into the castrate range by day 21 after depot administration. The safety profile of 10.8 mg. goserelin is comparable to that of the current monthly depot with the main side effects related to androgen deprivation.. The new long acting depot was pharmacologically equivalent, and well tolerated locally and systemically, and will offer added convenience to patients and health care personnel.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Testosterone

We determined whether 12 weeks of neoadjuvant testicular androgen ablation therapy using a luteinizing hormone-releasing hormone agonist could improve pathological outcomes in men undergoing radical retropubic prostatectomy for clinically localized (stages T1C, T2A and T2B) prostatic carcinoma.. A total of 56 participants was randomized to receive either monthly injections of a luteinizing hormone-releasing hormone agonist at 4-week intervals followed by radical retropubic prostatectomy (28) or to undergo immediate radical retropubic prostatectomy alone (28). Operations were performed via similar technique and all prostatic specimens were processed histologically in their entirety.. There was no improvement in pathological outcome using luteinizing hormone-releasing hormone agonist preoperatively compared to surgery alone. Of 28 men undergoing immediate radical retropubic prostatectomy 23 had organ-confined (17) or specimen-confined (6) disease versus 22 of 28 who received luteinizing hormone-releasing hormone neoadjuvant therapy for 12 weeks preoperatively (16 with organ-confined and 6 with specimen-confined disease, p = 1.00). In addition, when the study population was analyzed by pretreatment prostate specific antigen (PSA) levels (10 ng./ml. or less, or greater than 10 ng./ml/) there was also no difference in pathological outcome (p = 0.65 for PSA greater than 10 and p = 0.32 for PSA less than 10).. Neoadjuvant androgen ablation therapy for 12 weeks before radical prostatectomy in patients with clinically localized adenocarcinoma of the prostate does not result in improved pathological outcomes.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatectomy; Prostatic Neoplasms; Treatment Outcome

This study was undertaken to evaluate the quality of life (QoL) of previously untreated patients with M1 prostate cancer before and during androgen-suppressive treatment. Assessment of QoL was included as an optimal component of EORTC protocol 30853, a phase III trial comparing LH-RH (luteinising hormone-releasing hormone) analogue combined with a non-steroidal anti-androgen versus orchiectomy in patients with M1 prostate cancer. At pretreatment and during the follow-up period, patients were asked to complete a questionnaire assessing their physical and psychosocial functioning, and their symptom levels. Physicians rated the patients' performance status, pain, urological symptoms and erectile function. Due to its optional nature, only a minority of the patients in the trial were recruited for the QoL investigation. 63 patients completed a pretreatment questionnaire, of whom 49 completed a second questionnaire at least once during the initial 15 month follow-up period. While statistically significant correlations were observed between patients' and physicians' ratings of physical functioning and pain, these were of only a moderate magnitude (r = 0.43 and 0.30, respectively). No significant association was observed between physicians' and patients' ratings of micturation problems or of erectile function. Before treatment, fatigue, pain and decreased social role and sexual functioning were the problems most frequently reported by patients. With an average of approximately 1 year follow-up, statistically significant improvements were observed in patients' self-reported urological symptoms and metastatic pain. No significant changes were noted for the other QoL domains assessed. The results of this study confirm earlier findings that physicians' ratings may not reflect accurately the functional health and symptom experience of their patients. Patient-based QoL questionnaires offer the most direct means of evaluating the subjective morbidity associated with prostate cancer and its treatment. To increase participation and compliance rates in future studies, it is recommended that QoL assessment be made mandatory in those clinical trials in which QoL is considered to be an important study endpoint.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Medical Staff, Hospital; Middle Aged; Orchiectomy; Patient Compliance; Prostatic Neoplasms; Quality of Life; Surveys and Questionnaires

Between January 1992 and September 1993, 813 patients with stage D2 prostate cancer were enrolled in a multicentre, double-blind (for antiandrogen therapy) trial and randomised to antiandrogen therapy with Casodex (bicalutamide, 50 mg once daily) or flutamide (250 mg three times daily) and to luteinising hormone-releasing hormone (LHRH) analogue therapy with Zoladex (goserelin, 3.6 mg every 28 days) or leuprolide (7.5 mg every 28 days). Time to treatment failure was the primary efficacy endpoint. At a median follow-up time of 49 weeks, there was a significant (p = 0.005) difference between groups in time to treatment failure in favour of Casodex plus LHRH analogue. Overall, 168 (42%) of 404 patients in the Casodex plus LHRH analogue group and 218 (53%) of 409 patients in the flutamide plus LHRH analogue group reached a treatment failure endpoint. Although a cause-specific treatment-failure analysis was not performed, the difference between groups in treatment failure attributed to adverse events (mainly diarrhoea) was evident primarily in the first 7 months of therapy. The difference between groups in treatment failure for objective progression was most evident after 1 year of therapy. With further follow-up (median time of 95 weeks), the result for time to treatment failure, although no longer statistically significant, were consistent with the previous finding of an improvement in time to treatment failure associated with Casodex plus LHRH analogue therapy. With a median of 95 weeks of follow-up, 34% of deaths had occurred. The survival analysis was not dissimilar between the 2 groups. At 49 weeks median follow up, the incidence of diarrhoea was significantly (p < 0.001) lower among patients in the Casodex plus LHRH analogue group. Diarrhoea led to withdrawal from therapy for 2 patients in the Casodex plus LHRH analogue group, compared with 25 patients in the flutamide plus LHRH analogue group. In conclusion, Casodex plus LHRH analogue is well tolerated and effective with an improvement in time to treatment failure over flutamide plus LHRH analogue. Survival was not dissimilar between the 2 treatment groups.

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Drug Synergism; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Nitriles; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Survival Analysis; Tosyl Compounds

The effects of pharmacotherapeutic complete androgen deprivation treatment for 2 months before radical retropubic prostatectomy (RRP) were investigated in an open study in 375 patients. Prostate volume, tumor staging and prostatespecific antigen (PSA) were investigated as clinical parameters. The RRP specimens were analyzed particularly in terms of tumor cell regressions, pathological tumor staging and grading. Before neoadjuvant therapy (NAT) the 375 patients were classified according to stage: 36 (9.6%) were T1B; 137 (46.1%) were T2, and 166 (44.3%) were T3 stage. After NAT, the clinical investigation (digital rectal examination + transrectal ultrasonography) gave an impression of a T0 stage in 11% of the T2 patients, and a T2 tumor stage in 39% of the T3 patients. The histopathological analysis of the initial T1B and T2 cases did not reveal any tumor in the RRP specimen in 11 (3.8%) cases, a pT2 tumor in 153 (73%) cases, and a pT3 tumor in 48 (23.5%) cases. In the patients initially classified as T3, a tumor was no longer found in 1 (0.6%) case, and a pT2 tumor was found in 48 (29.3%) cases and a pT3 tumor in 113 (67.7%) cases. Under NAT, the prostate volume fell by 34% in T3 tumors and by 24% in T2 tumors. The fall in PSA averaged 85% without significant differences in the individual tumor stages. A statistically significant correlation could not be demonstrated between the fall of PSA and the definitive pathological tumor stage. Tumor cell regressions were found in all preparations. The degree of regression was predominantly RII. These results document the direct effect on tumor cells of an inductive androgen-ablative pharmacotherapy. Regression and volume reduction of the tumor might lead to an improvement of the local surgical control. A final clinical evaluation of NAT will only be possible after long-term analysis of ongoing prospective, randomized studies.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Cyproterone Acetate; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Time Factors

A prospective randomised study was performed to test the hypothesis that total androgen ablation, achieved by combining an LHRH analogue, goserelin acetate (Zoladex), with an antiandrogen, cyproterone acetate (Cyprostat), is more effective than conventional monotherapy in delaying the time to progression of metastatic prostatic cancer. 525 patients were recruited at 18 UK centres between May 1986 and January 1989, 175 patients being allocated to each arm. Patients were clinically and biochemically assessed at 1, 2, 3, 6, 9 and 12 months after initiation of therapy and then every 6 months until a maximum duration of 48 months. There was no statistically significant difference in terms of median time to progression between the combination treatment arm and either monotherapy arm, although there was a statistically significant difference between goserelin acetate alone and cyproterone acetate alone, in favour of goserelin acetate (p = 0.016). All treatment regimens were well tolerated and cyproterone acetate reduced both tumour flare reactions and hot flushes in patients receiving goserelin acetate. It is concluded that total androgen ablation using cyproterone acetate (300 mg/day) and goserelin acetate (3.6 mg every 28 days) confers no advantage in terms of time to progression, to conventional monotherapy, but can reduce certain side effects caused by LHRH analogue treatment alone.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyproterone Acetate; Disease Progression; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Safety

The objective of this study was to document previously unreported anemia in prostate cancer patients treated with neoadjuvant combined androgen blockade (CAB) and pelvic radiotherapy (XRT).. Four institutions treated 141 patients (mean age +/- SD, 70.9 +/- 6.5 years) with zoladex 3.6 mg injection subcutaneous depot monthly and flutamide 250 mg orally three times per day for 2 months (CAB), followed by zoladex and flutamide with concurrent XRT (65-70 Gy) for 7-8 weeks.. After the XRT, the patients were randomized to receive no further treatment (Z- group, 71 patients) or zoladex alone (Z+ group, 70 patients) for 2 years. Hemoglobin (Hb) levels decreased > or = 1 g/dl (mean +/- SE, 2.1 +/- 0.1 g/dl) in 98/131 patients (75%) after 2 months of CAB, and > or = 2 g/dl (3.1 +/- 0.1 g/dl; range, 0.1-6.8 g/dl) in 106/131 patients (81%) after an additional 2 months of CAB with concurrent XRT. The decrease in Hb levels paralleled the decreased in testosterone levels. No evidence of blood loss or hemolysis was found.. There was no association between incidence or rate of Hb decrease and race, age, or pretreatment prostate-specific antigen (PSA) levels. However, the recovery from anemia after completion of CAB in African-Americans was slower than in Whites in the Z+ group (P < 0.04). Whereas grade 1 hematologic toxicity may occur in < 5% of the patients with zoladex alone, and approximately 6% with flutamide alone, in our study 81% showed mild to pronounced anemia. Since anemia has not been observed after treatment with XRT alone or XRT followed by zoladex, we conclude that the anemia was due to CAB. Recognition of this side effect should avoid unnecessary diagnostic evaluations.

Topics: Aged; Androgen Antagonists; Anemia; Antineoplastic Agents, Hormonal; Black People; Combined Modality Therapy; Drug Therapy, Combination; Flutamide; Goserelin; Hemoglobins; Humans; Male; Pelvis; Prostatic Neoplasms; Remission Induction; White People

A randomized, multicenter trial, double-blind for antiandrogen therapy, compared the antiandrogens bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue therapy (LHRH-A) in 813 patients with Stage D2 prostate carcinoma. An analysis of time to progression (median follow-up, 95 weeks) was performed to augment previous analyses of time to treatment failure and time to death.. Patients were randomly assigned 1:1 to double-blind antiandrogen therapy, receiving either bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), and were assigned 2:1 to LHRH-A with goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days). The primary endpoint of the trial was time to treatment failure, defined as an adverse event leading to withdrawal of randomized therapy, objective progression, death, or withdrawal from study therapy for any reason. Secondary endpoints were time to death, quality of life, and subjective response. The current analysis of time to progression included progression data collected prospectively for 561 patients (69%) and retrospectively for 252 patients (31%).. Disease progression occurred for 223 of 404 patients (55%) in the bicalutamide plus LHRH-A group and for 235 of 409 patients (58%) in the flutamide plus LHRH-A group. The hazard ratio for time to progression of bicalutamide plus LHRH-A to that of flutamide plus LHRH-A was 0.9 (two-sided 95% confidence interval [CI], 0.75 to 1.08; P = 0.26). The upper one-sided 95% CI was 1.05, which met the definition of equivalence (< 1.25).. At a median follow-up time of 95 weeks, bicalutamide plus LHRH-A and flutamide plus LHRH-A had equivalent time to progression.

Topics: Adenocarcinoma; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Double-Blind Method; Flutamide; Goserelin; Humans; Leuprolide; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds

To compare the pharmacodynamics and tolerability of the new goserelin acetate 10.8-mg depot with the 3.6-mg depot in patients with advanced prostate cancer during the first 3 months of therapy.. One hundred sixty patients were randomized in two comparative studies to receive either the 10.8-mg goserelin acetate depot every 12 weeks or the 3.6-mg goserelin acetate depot every 4 weeks for 12 weeks and then the 10.8-mg depot every 12 weeks thereafter. Data for pharmacodynamic assessments were collected prospectively, whereas clinical response data were collected retrospectively.. Serum testosterone profiles of the 10.8-mg goserelin acetate depot and the 3.6-mg goserelin acetate depot were similar; testosterone levels in both groups fell below castrate levels by day 21 after administration. Decreases in serum prostate-specific antigen level after 3 months of therapy were also similar in both groups: 94% with the 10.8-mg depot and 92.5% with the 3.6-mg depot. For all patients, the median time to progression was 152.7 weeks and the median time to death was 213.6 weeks. The safety profile of the 10.8-mg goserelin acetate depot was similar to that of the 3.6-mg depot; hot flashes was the most common adverse event. The incidence of injection site reactions was very low (2 [0.3%] of 614 administrations).. The new 10.8-mg depot was pharmacodynamically equivalent to the current 3.6-mg depot and was well tolerated, both locally and systemically. The observed times to progression and survival were as expected in this patient population. The 10.8-mg goserelin-acetate depot provided a dosing schedule that was convenient for the patient and the physician, and it has the potential to reduce health care costs while maintaining the quality of life in patients being treated for advanced prostate cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Retrospective Studies; Testosterone; Time Factors

In a recent study by the Casodex Combination Study Group, USA, patients in a flutamide (750 mg/day) plus LH-RH agonist group showed a high treatment failure rate, mainly due to flutamide-induced diarrhea and hepatotoxicity. Our current study was conducted to determine the optimal dose of flutamide for use in this type of combination therapy.. In a randomized, multicenter study, 30 patients (hormone untreated; stage C or D) were divided into 2 groups: flutamide 250 mg (125 mg x 2; 14 patients) and flutamide 375 mg (125 mg x 3; 16 patients, and each dose combined with either goserelin acetate (3.6 mg every 4 weeks) or leuprolide acetate (3.75 mg every 4 weeks). Goserelin and leuprolide were administered to patients in a 1:1 ratio. Flutamide monotherapy at a daily dose of 375 mg was determined to be the optimal dose in Japan in our previous phase II study. The endpoints of this pilot study were the objective response and adverse events during the 12-week treatment.. The objective response rate was 83.3% in the flutamide 250 mg group and 85.7% in the flutamide 175 mg group according to the Japanese response criteria for prostate cancer. Elevated PSA levels fell to within the normal range in 83.3% of the patients in the former group and in 93.3% of the patients in the latter group. One patient administered 250 mg of flutamide experienced diarrhea, while the serum GOT and/or GPT were elevated in 3 patients administered 250 mg of flutamide and 4 patients administered 375 mg of flutamide.. Based on the findings of this pilot study of maximal androgen-depletion therapy for advanced prostate cancer, 375 mg/day of flutamide is recommended in combination with an LH-RH agonist. Assessment of the effects of our recommended regimen on longer term survival, quality of life and antiandrogen withdrawal syndrome of patients treated requires additional patients and time for follow-up.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemical and Drug Induced Liver Injury; Diarrhea; Dose-Response Relationship, Drug; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms

In order to examine the usefulness of chemohormonal therapy, we conducted a multicentered randomized trial comparing hormonal therapy, using a luteinizing hormone-releasing hormone (LH-RH) agonist, with chemohormonal therapy, hormonal therapy plus cyclophosphamide (CPM), in patients with newly diagnosed clinical stage D prostatic cancer.. Between January 1991 and March 1995, 41 evaluable patients with stage D prostatic cancer were randomized into 2 groups: group A (hormonal therapy alone), goserelin acetate depot 3.6 mg subcutaneously every 4 weeks: group B (chemohormonal therapy), goserelin acetate depot 3.6 mg subcutaneously and CPM 1000 mg/m2 intravenously every 4 weeks. The responses to the therapies were evaluated based on the criteria of The Japanese Urological Association.. There were no significant differences between the 2 groups with regard to objective and subjective response rates. No advantage in chemohormonal therapy was observed in the survival rate and progression-free survival rate. However, the survival rate and progression-free survival rate of responders were significantly higher than those of nonresponders in both groups. When the results were categorized by histologic grade patients with poorly-differentiated adenocarcinoma had significantly higher response rates, survival rates, and disease-progression-free survival rates in Group B compared to similar patients in Group A.. We conclude that chemohormonal therapy does not definitely improve the clinical response and prognosis of patients with stage D prostatic cancer; however, for patients with poorly-differentiated adenocarcinoma, chemohormonal therapy is a useful treatment.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Antineoplastic Agents, Hormonal; Cyclophosphamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prospective Studies; Prostatic Neoplasms; Survival Analysis

Prognostic factors were evaluated in advanced loco-regional (M0) or distant metastatic (M1) prostatic carcinoma treated with total androgen blockade (flutamide with either orchiectomy of LHRH-analogues), in 546 patients from a Belgian multicentric study. After a mean follow-up of 16.5 months (maximum 37 months) 113 (21%) patients had progressed (90 were patients with M1 disease (31%)). The estimated median progression-free survival exceeded 37.5 months. The results of a univariate analysis show that the following parameters are important prognostic factors with respect to progression-free survival in these patients: M stage, G grade, ECOG performance status, weight loss, concomitant disease, pain, dysuria and haemoglobin (Lee-Desu test, p < or = 0.01). From a multivariate analysis (Cox regression) the following prognostic factors were indicative of a decrease in progression-free survival: M1 stage, high initial G grade, ECOG performance status > I, high serum PSA, presence of concomitant disease, presence of pain and absence of dysuria. Age did not appear to be a statistically significant prognostic factor.

Topics: Aged; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Castration; Combined Modality Therapy; Disease-Free Survival; Flutamide; Goserelin; Humans; Male; Middle Aged; Multivariate Analysis; Prognosis; Prostatic Neoplasms; Triptorelin Pamoate

Single-agent therapy with bicalutamide, a nonsteroidal antiandrogen, was compared with castration, either surgical or medical, in patients with untreated Stage D2 prostate cancer.. In an open, randomized, multicenter trial, patients were randomized to treatment with 50 mg bicalutamide (n = 243) once daily or to castration (n = 243), either orchiectomy or depot injection of goserelin acetate every 28 days. Primary efficacy endpoints were times to treatment failure and objective disease progression and survival. Assessments included review of measurable metastases, prostate dimensions, Eastern Cooperative Oncology Group performance status, pain, analgesic requirements, and quality of life responses.. The median duration of therapy was 39 weeks for bicalutamide-treated patients and 42 weeks for castrated patients; treatment failure occurred in 53% and 42% and disease progression in 43% and 33%, respectively. Treatment effects favored castration for both endpoints (P < or = 0.002), with hazard ratios (bicalutamide:castration) of 1.54 (95% confidence interval [CI], 1.18 to 2.00) for time to treatment failure and 1.6 (95% CI, 1.19 to 2.15) for time to disease progression. From the 1-year survival analysis, the hazard ratio for probability of death was 1.29 (95% CI, 0.96 to 1.72). Thus far, with a median follow-up of 86 weeks, median survival has not been reached in either group. Changes from baseline in several quality of life variables were significantly different (P < or = 0.01) between treatment groups periodically from months 1 to 6, and all favored bicalutamide. Overall, the antiandrogen was well tolerated compared with castration; with bicalutamide, hot flushes occurred less often and breast tenderness and gynecomastia more often.. Although a dosage of 50 mg of bicalutamide once daily was not as effective as castration, the favorable quality of life outcomes and the low incidence of nonhormonal adverse events provide reasons to evaluate bicalutamide, as a single therapeutic agent, at higher doses.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Follow-Up Studies; Goserelin; Humans; Logistic Models; Male; Nitriles; Orchiectomy; Prostatic Neoplasms; Quality of Life; Remission Induction; Survival Rate; Tosyl Compounds; Treatment Failure; United States

To compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer.. Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days).. With a median duration of follow-up of 49 weeks, time to treatment failure, the primary endpoint, was significantly (P = 0.005) better for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group. Patients in the flutamide plus LHRH-A group were 34% more likely to fail treatment over the given time period, as indicated by the hazard ratio of 0.749 (95% confidence interval, 0.61 to 0.92) for bicalutamide plus LHRH-A to flutamide plus LHRH-A. Results for secondary endpoints (survival, quality of life, and subjective response) were similar between groups. Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group, compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001).. In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is well tolerated and provides superior efficacy to flutamide plus LHRH-A with respect to time to treatment failure. Assessment of the effects of these regimens on longer term survival requires additional time for follow-up.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Confidence Intervals; Double-Blind Method; Flutamide; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Nitriles; Proportional Hazards Models; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Regression Analysis; Survival Rate; Tosyl Compounds; Treatment Failure

To test the feasibility of using intermittent androgen suppression in the treatment of prostate cancer by taking advantage of the reversible action of medical castration.. Observations were made on a group of 47 patients (clinical Stage D2, 14; D1, 10; C, 19; B2, 2; and A2, 2) with a mean follow-up time of 125 weeks. Treatment was initiated with combined androgen blockade and continued for at least 6 months until a serum prostate-specific antigen (PSA) nadir was observed. Medication was then withheld until the serum PSA increased to a mean value between 10 and 20 ng/mL. This cycle of treatment and no treatment was repeated until the regulation of serum PSA became androgen independent.. The first two treatment cycles lasted 73 and 75 weeks, with a mean time off therapy of 30 and 33 weeks and an overall mean percentage time off therapy of 41% and 45%, respectively. The mean time to achieve a nadir level of serum PSA was 20 weeks in cycle 1 and 18 weeks in cycle 2. Serum testosterone returned to the normal range within 8 weeks (range, 1 to 26) of stopping treatment. The off-treatment period in both cycles was associated with an improvement in sense of well-being and the recovery of libido and potency in the men who reported normal or near-normal sexual function before the start of therapy. In 7 patients with Stage D2 disease, the cancer progressed to an androgen-independent state. The mean and median times to progression were 128 weeks and 108 weeks, respectively. Seven patients have died, 1 from a noncancer-related illness, with mean and median overall survival times of 210 weeks and 166 weeks, respectively.. Prostate cancer is amenable to control by intermittent androgen suppression. This approach affords an improved quality of life when the patient is off therapy. It also results in reduced toxicity and cost of treatment and possibly delays tumor progression. Whether survival is affected in a beneficial or adverse way remains to be studied in a randomized, prospective study.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Cyproterone Acetate; Diethylstilbestrol; Drug Therapy, Combination; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Time Factors

To compare the efficacy and safety of goserelin and orchiectomy in patients with stage D2 prostate cancer.. A randomized, open, multicenter study was conducted in 283 patients. Patients were allocated to goserelin, 3.6 mg every 28 days or to orchiectomy. Study end points were endocrine response, objective response, time to treatment failure, survival, and tolerability. Objective response was based on modified criteria of the National Prostate Cancer Project.. Serum testosterone decreased from baseline to castrate levels by week 4 in each group and remained below castrate levels thereafter. Acid phosphatase and alkaline phosphatase concentrations also decreased in each group. The goserelin and orchiectomy groups had similar results for objective response (82% versus 77%) and had similar medial times to treatment failure (52 versus 53 weeks) and survival (119 versus 136 weeks). No significant interactions between treatments and prognostic factors were observed. Adjusting for baseline testosterone concentration had no effect on survival outcome. Race had no influence on outcome or efficacy end points. Common adverse events in both groups were pain, hot flushes, and lower urinary tract symptoms.. Goserelin is well tolerated and as effective as orchiectomy in patients with Stage D2 prostate cancer.

Topics: Aged; Follow-Up Studies; Goserelin; Humans; Male; Orchiectomy; Proportional Hazards Models; Prostatic Neoplasms; Survival Analysis; Time Factors; Treatment Failure

Androgen deprivation therapy before and during radiation therapy could, by reducing tumor volume, increase local tumor control, disease-free survival, and overall survival in patients with locally advanced adenocarcinomas of the prostate.. In a randomized controlled clinical trial, patients with large T2, T3, and T4 prostate tumors, but no evidence of osseous metastasis, were randomized to receive goserelin 3.6 mg subcutaneously every 4 weeks and flutamide 250 mg orally three times daily 2 months before and during the radiation therapy course (Arm I) compared with radiation therapy alone (Arm II). Pelvic irradiation was administered with 1.8 to 2.0 Gy per day to a total dose of 45 +/- 1 Gy followed by a boost to the prostate target volume to a total dose of 65 to 70 Gy.. Of 471 randomized patients, 456 were evaluable, 226 on Arm I and 230 on Arm II. With a median potential follow-up of 4.5 years, the cumulative incidence of local progression at 5 years was 46% in Arm I and 71% in Arm II (P < 0.001). The 5-year incidence of distant metastasis on Arms I and II was 34% and 41%, respectively (P = 0.09). Progression-free survival rates including normal prostate-specific antigen (PSA) levels for 396 patients with at least one PSA recorded were 36% in Arm I and 15% in Arm II at 5 years (P < 0.001). At this time, no significant difference in overall survival could be detected (P = 0.7).. Short-term androgen deprivation with radiation therapy results in a marked increase in local control and disease-free survival compared with pelvic irradiation alone in patients with locally advanced carcinoma of the prostate. Long-term surveillance is required to assess effects on overall survival.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Combined Modality Therapy; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms

To eliminate the initial testosterone (T) surge and prevent the risk of flare-up induced by the first administration of luteinizing hormone-releasing hormone (LH-RH) analogue, we examined the effectiveness of short-term combination therapy with diethylstilbestrol (DES). Sixteen previously untreated patients with prostate carcinoma (Stage C: 4 cases, Stage D2: 12 cases) were randomly assigned to 4 groups. Each group included 4 patients. Group 1 received DES (500 mg daily injection) for 7 days, staring before the first subcutaneous injection of luteinizing hormone releasing hormone (LH-RH) analogue (3.6 mg of Zoladex depot); Group 2 received 500 mg of DES injection for 7 days prior to the initiation of therapy with the LH-RH analogue, and moreover received a DES injection for 7 days; Group 3 received 500 mg of DES injection for 7 days simultaneously with the first injection of the LH-RH analogue; Group 4 was pretreated with 500 mg of DES injection for 7 days prior to the initiation of therapy with the LH-RH analogue, with additional DES injection for 3 days. In groups 1, 2 and 4 the level of T decreased during the 7 days of DES therapy, and at 3 days after the first injection of LH-RH analogue increased again. The mean T value in groups 1, 2 and 4 decreased by 33.2 +/- 27.6% (mean +/- SE), 20.5 +/- 20.8%, 13.2 +/- 9.8%, respectively, at the day of the first injection of LH-RH analogue, and increased by 75.2 +/- 21.6%, 70.7 +/- 63.4%, 56.7 +/- 46.4%, respectively, at 3 days after the first injection of LH-RH analogue.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Diethylstilbestrol; Drug Administration Schedule; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Testosterone

A new longer-acting depot formulation containing 10.8 mg Zoladex administered every 12 weeks was compared to the 3.6-mg Zoladex depot administered every 28 days, in a randomised trial in patients with advanced prostatic carcinoma in which pharmacodynamic efficacy and safety were assessed. Effective induction of mean serum testosterone suppression into the surgically castrate range by 21 days and maintenance of suppression for the duration of therapy was achieved with both the 3.6-mg and the 10.8-mg depot formulations. The Zoladex 10.8-mg depot was well tolerated both locally and systemically. This new formulation which is equivalent to three successive 3.6-mg depots will provide a more convenient dosing regime for both patient and doctor in this indication.

Topics: Aged; Aged, 80 and over; Delayed-Action Preparations; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Testosterone

Neoadjuvant total androgen ablation therapy leads to involutional changes in prostatic carcinoma and may have the potential to downstage operable prostate cancers. We studied 27 clinically localized prostatic carcinomas after 3 months of combined treatment with a luteinizing hormone-releasing hormone agonist, goserelin acetate, and the antiandrogen flutamide, followed by radical retropubic prostatectomy, for changes in the serum prostate-specific antigen (PSA) level, changes in prostatic volume, therapy-induced histopathologic changes, DNA ploidy, and proliferative activity. Ten hormonally untreated, grade-matched prostatic adenocarcinomas served as controls. The mean pretherapy serum PSA level was 17.5 ng/ml, and posttherapy PSA levels were all < 4.0 ng/ml, with 18 men having undetectable levels. The mean reduction in prostatic volume following hormonal therapy was 37% (range 16-52%). Pathologic staging confirmed 20 pT2N0, six pT3N0, and one pT3N1. All prostates showed residual adenocarcinoma (extremely focal in seven cases [26%] with loss of glandular architecture, cytoplasmic vacuolization, and nuclear pyknosis. High-grade adenocarcinoma was nondiploid in 25% of hormonally treated prostates and 80% of 10 untreated controls. Immunostaining for proliferating cell nuclear antigen showed > 10% nuclear reactivity in 33% of treated carcinomas and 90% of untreated carcinomas. In conclusion, 3 months of neoadjuvant androgen ablation for localized prostatic carcinoma significantly lowers serum PSA and prostatic volume and produces involutional changes in residual carcinomas that mimic high-grade disease. However, pretreated carcinomas have predominantly a diploid DNA content and low proliferative activity as opposed to untreated carcinomas. Thus, grading of pretreated adenocarcinomas by conventional methods may be misleading. Preoperative total androgen ablation has a profound effect on a subset of prostatic carcinoma cells, possibly by facilitating programmed cell death.

Topics: Adenocarcinoma; Cell Division; Combined Modality Therapy; Diploidy; Flutamide; Goserelin; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Topics: Delayed-Action Preparations; Drug Administration Schedule; Goserelin; Humans; Injections, Subcutaneous; Male; Prostatic Neoplasms

This trial compares Casodex (ICI 176,334) monotherapy with the combination of castration (medical or surgical) plus nilutamide. The trial is now closed to entry, 270 patients having been recruited from 32 French centres. As it is too early to present efficacy data, only patient characteristics and interim tolerability data appear in this paper. In the combined treatment group, interstitial pneumonitis (4.5%) was observed, leading to withdrawal from the trial. Other adverse events leading to withdrawal included dyspnoea and ocular problems. There was also 1 case of hepatitis in this treatment group. In the Casodex treatment group, only 6 patients (as compared with 13 in the combined treatment group) withdrew from the trial because of adverse events. As expected with this group, the adverse events were mainly pharmacological effects of an anti-androgen as monotherapy. In the majority of patients, the effects of gynaecomastia and breast tenderness did not result in withdrawal.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Combined Modality Therapy; Goserelin; Humans; Imidazoles; Imidazolidines; Male; Nitriles; Orchiectomy; Prostatic Neoplasms; Tosyl Compounds

Topics: Chemotherapy, Adjuvant; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms; Radiotherapy, High-Energy

Topics: Chemotherapy, Adjuvant; Flutamide; Goserelin; Humans; Male; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms

Casodex (ICI 176,334) is a non-steroidal anti-androgen, which has a half-life compatible with once-daily oral dosing. In an open, phase II study on 267 patients given Casodex, 50 mg/day, an overall objective response (i.e. partial regression) was seen in 55.5% of patients (146 of 263) with a further 15.6% (41 of 263) having stable disease. Two of three randomized, phase III studies conducted with Casodex, 50 mg/day, showed it to be inferior to castration (either medical or surgical) on time to treatment failure and time to progression. A subsequent overview analysis of survival from these three studies showed a statistically significant difference in favour of castration. Prostate specific antigen (PSA) at 3 months correlated well with clinical outcome in the phase III studies of Casodex, 50 mg/day; a greater fall in PSA at 3 months was observed with Casodex, 100 and 150 mg/day, in an open dose-ranging study. As no significant tolerability issues were reported, further investigation of Casodex at these higher doses is in progress. All studies in which Casodex has been investigated have shown it to be a well-tolerated anti-androgen with a good side-effect profile compared with those reported for other available non-steroidal anti-androgens.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Goserelin; Humans; Male; Nitriles; Orchiectomy; Prostatic Neoplasms; Tosyl Compounds

Topics: Combined Modality Therapy; Erectile Dysfunction; Flutamide; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testis; Testosterone

In a prospective, randomized open study, a long-acting LHRH agonist (Zoladex) was compared with polyoestradiol phosphate (Estradurin), both widely used in Finland for palliative treatment of prostatic carcinoma, as regards efficacy and side effects. Of the 236 enrolled patients, 129 were randomized to receive LHRH agonist and 107 to oestrogen treatment. The median follow-up was 25 months. Reduction of prostatic volume was quicker and more effective in the LHRH than in the oestrogen group, and serum testosterone concentrations fell to castration level after 1 month and 1 year, respectively. In locally advanced (M0) and histologically well or moderately differentiated tumours, LHRH agonist therapy was considerably more effective than oestrogen as regards time to progression of the carcinoma, but in metastatic (M1) and histologically poorly differentiated tumours both methods gave similar results. Cardiovascular complications showed equal incidence in both groups. LHRH agonist therapy thus seemed to be more effective than polyoestradiol phosphate against locally advanced prostatic cancer in the doses used.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Estradiol; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Testosterone

Topics: Delayed-Action Preparations; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms; Retrospective Studies

The optimal treatment of prostate cancer in clinical stage C is controversial. On the one hand a disease still confined by definition, as stage C is, should require a curative therapy such as surgery or radiotheratherapy. On the other hand the known fact that 50% of stages C are pathological stages D1, should propose a palliative, even thou effective, medical treatment. In fact both choices are questionable. A radical treatment risks being insufficient, whereas a palliative does not allow for giving a chance of a theoretically possible cure. In an attempt to resolve this difficulty, a sort of compromise is proposed. The patients should be initially treated with radical radiotherapy, and only in the case of progression will standard hormonotherapy be given. Thanks to this behaviour a possibility of cure is maintained, and, in addition, when suffering a progression the patients are likely to benefit from hormonotherapy owing to the fact that they are not pretreated. From 1985 to 1991 forty-eight clinical stage C patients were observed. They were given the choice between two treatments after explaining the theoretical benefits and disadvantages of both. Treatment A consisted of cobalt-60 therapy followed by hormonotherapy after progression, treatment B in primary ormonotherapy with LH-RH analogue +/- Flutamide. Twenty patients opted for treatment A and 21 for B.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Combined Modality Therapy; Flutamide; Follow-Up Studies; Goserelin; Humans; Infant; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms

To determine if initial chemo-hormone therapy (estramustine phosphate) of metastatic prostate carcinomas can lengthen the period until progression, compared with hormone treatment (goserelin) alone? The time to progression, side effects and prognostic factors were assessed.. The prospective phase III study (II 86 until V 91) involved 243 patients randomized consecutively in two groups. Progress was assessed according to NPCP criteria.. The following prognostic factors were established to be significant: metastatic status, metastatic bone pain, alkaline phosphatase and performance status. No difference was observed between the two methods of treatment in time to progression. However on stratifying according to groups with the same prognostic factors, progression in the high risk group occurred at a later stage during treatment with estramustine than during pure hormone treatment. The quality of life was clearly more heavily restricted by side effects from estramustine.. Thus, when comparing these treatments, there were no statistically significant differences. Patients in the high risk groups with unfavorable prognosis factors benefitted from the chemo-hormone treatment with estramustine phosphate.

Topics: Adenocarcinoma; Aged; Estramustine; Goserelin; Humans; Male; Prognosis; Prospective Studies; Prostatic Neoplasms; Risk Factors; Time Factors

Topics: Chemotherapy, Adjuvant; Goserelin; Humans; Male; Prostatic Neoplasms; Radiotherapy Dosage; Time Factors

In response to the first administration of a luteinizing hormone-releasing hormone (LHRH) agonist, the secretion of pituitary gonadotropin increases sharply and gives rise to a transient surge in the concentration of serum testosterone. This effect reaches a peak 4 to 7 days after the start of therapy and results in the onset of clinical symptoms and signs of tumor flare in 5% to 10% of patients.. To determine whether the effects of the LHRH-induced flare reaction are preventable, cyproterone acetate (100 mg) and low-dose diethylstilbestrol (0.1 mg) were administered daily for 4 weeks to inhibit the pituitary before the initiation of therapy with a depot LHRH agonist, goserelin acetate (3.6 mg every 4 weeks). Diethylstilbestrol was stopped after 8 weeks to eliminate associated minor toxicity while administration of cyproterone acetate was continued to suppress vasomotor symptoms. Twenty-four men with histologically confirmed prostate cancer were enrolled in the study: 6 with Stage C, 2 with Stage D1, and 16 with Stage D2 disease.. Lead-in therapy reduced the concentration of serum testosterone into the castrate range within 1 week, and no significant change was observed in the mean level after administration of goserelin acetate. Neither was there an effect on the initial rate of normalization of serum prostate specific antigen (PSA); normal PSA values were obtained in 50% of patients after 10 weeks and in 70% after 32 weeks. In the subgroup of patients with Stage D2 disease, longer median survival was predicted by a normal serum PSA, either stable or decreasing, after 32 weeks of treatment. The regimen was well tolerated with a low incidence of hot flushes.. These results imply that in the absence of LHRH-induced tumor flare, prognosis is related to the ability of therapy to maintain a PSA nadir in the normal range.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Cyproterone Acetate; Diethylstilbestrol; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Pituitary Gland; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Survival Rate; Testosterone

Radical prostatectomy is an excellent form of treatment of pathologically organ-confined prostatic carcinoma. However, most clinically localized prostatic cancers have pathologic evidence of extracapsular spread, limiting the effectiveness of radical surgery in curing this disease. To improve the organ-confined rate of prostate cancer, we studied the effect of preoperative or neoadjuvant androgen deprivation therapy (ADT). Our initial attempts focused on downstaging locally advanced tumors (T3) with neoadjuvant diethylstilbestrol (3 mg/d). Our study of 59 patients revealed that although there were significant clinical signs of downstaging, most patients still had extraprostatic disease. However, a subset of patients demonstrated marked pathologic regression, so we initiated a nonrandomized but controlled study of neoadjuvant ADT (goserelin acetate and flutamide for 3 months) followed by radical prostatectomy in patients with clinically localized prostate cancer. Of 72 control and 69 study patients, the rate of organ-confined disease was 48% and 74% (including 4% with no detectable residual carcinoma), respectively. In addition, the margin-positive rate was 33% and 10%, respectively. As demonstrated in the previous study, changes in serum prostate-specific antigen, transrectal ultrasonographic evaluations, and digital rectal examinations could not predict those patients with favourable pathology. Our results suggest that neoadjuvant ADT may improve the pathologic stage in some prostatic carcinomas and is worthy of further investigation in the efforts to augment the effectiveness of radical prostatectomy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Flutamide; Goserelin; Humans; Male; Preoperative Care; Prostatectomy; Prostatic Neoplasms

Two hundred consecutive patients with presumed localized prostate cancer had radical prostatectomy alone (n = 119) or were treated for an average period of 3 months with combination therapy using the antiandrogen flutamide and one luteinizing hormone-releasing hormone (LHRH) agonist (Lupron or Zoladex). The positive margins decreased from 35.3% in the group undergoing prostatectomy alone to 11.5% in the group of men who received combination therapy before radical prostatectomy. In 41 apical tumors, the incidence of positive margins decreased from 50% in the control group to 18.6% in the combination therapy group. In stage C disease, the incidence of positive tumor showed a tendency to decrease with the extended duration of endocrine treatment with a rate of 37.5% after 3 months and 16.7% after 6 months. Whether the decreased incidence of positive surgical margins will all translate into prolonged survival remains to be verified by long-term follow-up of these patients. However, the initial results obtained in the present study are very encouraging.

Topics: Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Flutamide; Goserelin; Humans; Leuprolide; Male; Middle Aged; Preoperative Care; Prostatectomy; Prostatic Neoplasms

This European Organization for Research and Treatment of Cancer (EORTC) trial 30853 is the fifth EORTC--Genitourinary Group randomized phase III trial of endocrine treatment for patients with newly diagnosed metastatic prostate cancer. Special attention was given to the assessment of response and/or progression. Each of the following factors was assessed separately as nonspecific and subjective criteria of response or progression: performance status, pain, alkaline and acid phosphatase, hemoglobin, urinary symptoms, and prostate-specific antigen (PSA). Objective progression was based on measurable disease. The observed sequence of progression was: (1) protein-specific antigen; (2) bone; (3) pain; and (4) performance status. Protein-specific antigen, an optional parameter, was the first sign of progression in more than 50% of patients whose disease had progressed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Flutamide; Goserelin; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Orchiectomy; Prospective Studies; Prostatic Neoplasms

In a multicenter trial conducted by the Danish Prostatic Cancer Group, 264 patients with advanced prostate cancer were randomized either to undergo bilateral orchiectomy or to receive combination treatment with goserelin acetate and flutamide. This report is an update of that study, covering a median follow-up for survival of 57 months. Of 262 patients who were evaluated, 208 have died. As noted in earlier analyses of this study, no differences in time to progression and cause-specific and overall survival could be identified between the two treatment groups. In conclusion, the combination of goserelin and flutamide was not clinically superior to bilateral orchiectomy in the treatment of advanced prostate cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Survival Rate

A total of 327 patients with metastatic prostate cancer were randomized to receive bilateral orchiectomy or treatment with Zoladex and flutamide. The trial aimed to evaluate subjective and objective time to progression, survival, and incidence and duration of response. Strict quality control and evaluation by independent ad hoc committees were organized. Progression was assessed for each of 13 parameters. The time to subjective and objective progression was in favor of the combination treatment, with statistical significances of P = 0.009 and P = 0.008, respectively. This delay in objective progression resulted in increased survival in favor of the combination treatment for death by cancer (P = 0.02) or overall survival (P = 0.05). Survival differences were more marked in the patients with better prognostic factors. The clinical significance of these differences for the individual patient requires detailed assessment.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Flutamide; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Survival Rate

Topics: Antineoplastic Combined Chemotherapy Protocols; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms; Survival Rate

Subjective quality-of-life assessments obtained from investigators and patients were compared in a subset of 76 patients from an EORTC study (protocol 30853) on metastatic prostatic carcinoma. In this study the therapeutic effect of orchiectomy was compared with a luteinizing hormone-releasing hormone analogue depot preparation and flutamide in 327 patients in total. Pretreatment, 6- and 12-month quality-of-life assessments revealed large variations between the patients' and the investigators' evaluation of performance status and sexual status (potency). Correlation analysis showed that reduced social life, impaired sexual potency and fatigue played important roles in overall psychological well-being. It was concluded that quality-of-life assessments obtained by self-administration questionnaires is a feasible approach and provides a tool to evaluate the benefits of treatment in prostate cancer.

Topics: Activities of Daily Living; Flutamide; Goserelin; Humans; Interpersonal Relations; Male; Orchiectomy; Pain; Prostatic Neoplasms; Quality of Life; Sexual Behavior; Surveys and Questionnaires; Urination Disorders

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

Topics: Aged; Bone Neoplasms; Combined Modality Therapy; Drug Therapy, Combination; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prognosis; Prostatic Neoplasms; Survival Analysis

From March 1987 to December 1990, 373 patients with stage C and D prostate cancer were randomized to receive either goserelin acetate alone or goserelin acetate plus flutamide. At a median follow-up time of 24 months, there was no significant difference in the response rate, progression-free and overall survival between the two treatment groups. In particular, median time to progression was 18 months in the goserelin arm and 24 months in the combined treatment arm (P = 0.09). However, median time to progression in stage D patients was 12 months in both treatment groups. Median time to death was 32 and 34 months, respectively. The combination regimen produced a more rapid normalisation of prostatic acid phosphatase levels and a prompt relief of bone pain. However, significantly more patients in the combination arm experienced treatment-related side-effects such as diarrhoea and increases in transaminase levels. The concurrent use of goserelin acetate and flutamide does not seem to significantly improve the results that can be achieved with goserelin acetate alone.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Flutamide; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Time Factors

An open randomised Phase III trial was conducted of the depot GnRH analogue goserelin (Zoladex) versus stilboestrol (3 mg/day) in patients with advanced or metastatic prostate cancer. The study included 250 patients and the median follow-up was 43 months. In the Zoladex arm the time to first response was achieved earlier and more patients reported an improvement in symptoms. There was no statistically significant difference between the Zoladex and the stilboestrol arms with regard to survival and time to treatment failure. A major reason for treatment failure was the preponderance of adverse events in patients receiving stilboestrol. It is suggested that stilboestrol should no longer be used for prostate cancer when equally effective alternative treatments are available.

Topics: Aged; Aged, 80 and over; Buserelin; Diethylstilbestrol; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Time Factors; Treatment Outcome

589 patients from 10 countries are recruited into a multicentre randomised trial comparing Zoladex with a combination of Zoladex-Depot + flutamide. Zoladex was administered as a depot injection every 28 days and flutamide was given as 3 x 250 mg tablets daily. Patients with histologically confirmed locally advanced (T3/T4) or metastatic (M1) carcinoma were included. Patients with previous hormonal manipulation and/or chemotherapy were excluded. 65% of patients had metastatic disease. Both treatment groups were balanced (T-category, histology, metastases, performance status). An analysis of subjective and objective response, time to response and time to progression has shown no statistically significant difference. A survival analysis after a median follow-up of 24 months has shown no statistically significant difference between the two treatment groups (p = 0.47).

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Delayed-Action Preparations; Flutamide; Goserelin; Humans; Male; Neoplasm Recurrence, Local; Prostate; Prostatic Neoplasms

When present at diagnosis or when developing in the course of disease, the presence of bone metastases from prostate cancer is generally considered an indication to begin endocrine therapy, as this is clearly the most effective form of treatment for this problem. Endocrine therapy can stop progression of prostate cancer in 80-85% of cases. Endocrine therapy can relieve pain, prevent pathologic fractures, and prevent neurologic complications from bone metastases from prostate cancer. Rarely, bone scans may become normal after the start of endocrine therapy, but partial improvement or stabilization of bone scans are more commonly seen. While endocrine therapy has been the first line of treatment of metastatic prostate cancer for the past 50 years, the recent development of newer forms of endocrine therapy have increased the options in the past few years. In addition to orchiectomy and estrogens, newer alternatives include inhibitors of androgen synthesis, the class of agents termed "antiandrogens", and luteinizing hormone releasing-hormone (LHRH) analogues either alone or in combination. Orchiectomy causes a prompt fall in serum testosterone and is regarded by many as the "standard" form of endocrine therapy, but there is concern about the psychologic impact of surgery. Estrogens are being used less frequently today because of their real or potential side-effects, including cardiovascular and thromboembolic complications. The development of analogues of LHRH has resulted in another major choice for endocrine therapy, and one which is therapeutically equivalent to orchiectomy or estrogens. Since LHRH analogues may cause an early rise or "flare" in serum testosterone before it drops to castrate level, these agents should not be given alone to patients with severe pain or neurologic problems. The newly available antiandrogen flutamide can block the "flare", and may also improve survival when used with LHRH analogues or orchiectomy, especially when disease is less advanced. Not all studies of "combination therapy" support this conclusion. However, the use of flutamide is increasing significantly in the United States. Both the LHRH analogues and flutamide are fairly safe, but they are very expensive. Their use, in combination, is likely to become a progressively more common form of initial endocrine therapy in the future. The growing application of prostate specific antigen (PSA) as a tumor marker for prostate cancer has made the difficulty in interpreting chang

Topics: Actuarial Analysis; Androgen Antagonists; Bone Neoplasms; Combined Modality Therapy; Diethylstilbestrol; Estrogens; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Ketoconazole; Leuprolide; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Remission Induction; Spironolactone; Survival Rate

Topics: Adenocarcinoma; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Male; Neoplasm Staging; Orchiectomy; Patient Satisfaction; Prostatic Neoplasms; Survival Rate

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

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Buserelin; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prospective Studies; Prostatic Neoplasms; Testosterone

The independent prognostic factors affecting survival were assessed in 240 men undergoing treatment for metastatic prostate cancer as part of a randomized clinical trial comparing the gonadotropin releasing hormone analogue Zoladex (goserelin acetate implant) with castration. In a multivariate analysis, the most highly significant predictors were the presence or absence of bone pain, serum testosterone levels, serum alkaline phosphatase levels, and performance status. Patients with all four factors favorable for survival had a 2-year survival rate of 84% as compared with only 8% for patients with none of the four factors favorable for survival. No other factors were significant. A separate analysis of serum testosterone levels revealed that the higher the pretreatment serum testosterone level, the greater the survival rate. Compared with patients with serum testosterone levels less than 6.9 nmol/L, significant differences in survival were observed for patients with serum testosterone levels of 10.4 to 13.9, 13.9 to 17.3, and over 17.3 nmol/L. These results have important implications for the design and analysis of future clinical trials of hormone therapy and for counseling patients regarding the short-term prognosis of their disease.

Topics: Alkaline Phosphatase; Buserelin; Follow-Up Studies; Goserelin; Humans; Male; Multivariate Analysis; Orchiectomy; Pain; Prognosis; Prospective Studies; Prostatic Neoplasms; Survival Analysis; Testosterone

Zoladex plus flutamide significantly delays the time to progression (subjective, objective, first progression) compared with orchiectomy, but no difference in survival (death from all causes or from malignant disease) could be detected. Thus, a delay in the appearance of progression has not improved survival. In fact, the duration of survival after progression tends to be shorter on Zoladex plus flutamide. There is thus no evidence to suggest any survival benefit with Zoladex plus flutamide. The quality control of our data revealed acknowledged problems in defining responses in patients with advanced prostate cancer. The review of the Bone Scan Committee provided the data for Tables 5 to 7. These data must provoke some reflections and emphasize once again the heterogeneity of the studied patient population. Table 4 on pain response after 4 weeks is just one of the many items to be analyzed by the committees for response criteria and quality of life. We expect that the other trials face similar problems. More work and patience are needed to obtain a firm answer to this clinical problem. These efforts will never be wasted, however, because the combined results of these trials will increase our knowledge of the treated history of prostate cancer and will, we hope, indicate a net treatment benefit in some subsets of patients. An individually tailored treatment for each patient selected from the anonymous mass of cases of advanced prostate cancer would be the highest reward of our continued collaboration with all the study groups.

Topics: Aged; Buserelin; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms

This open, prospective study was conducted to compare ZOLADEX (goserelin acetate implant) and diethylstilbestrol (DES) in the treatment of stage D2 prostate cancer. Sixty-seven patients were allocated to receive 3.6 mg of ZOLADEX every 28 days by subcutaneous injection (n = 48) or 3 mg of DES daily by oral administration (n = 19). Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dl) within one month of therapy in each group and remained so for up to 120 weeks. According to modified criteria of the National Prostatic Cancer Project, 88% of patients in the ZOLADEX group and 84% in the DES group were objective responders. Time to treatment failure and survival were not significantly different between groups, yet the confidence limits for the hazard ratios were wide. ZOLADEX was better tolerated than DES. We conclude that ZOLADEX is an alternative to DES in patients with stage D2 prostate cancer.

Topics: Aged; Antineoplastic Agents; Buserelin; Diethylstilbestrol; Drug Implants; Follow-Up Studies; Goserelin; Humans; Male; Prostatic Neoplasms

Between November 1983 and February 1986, 358 patients with previously untreated metastatic prostatic carcinoma entered a multicentre, randomised trial in the United Kingdom and the Republic of Ireland, in which the LHRH analogue Zoladex (ICI Pharmaceuticals PLC), administered subcutaneously every 28 days, was compared with orchiectomy. Both treatments were equally effective in lowering serum testosterone concentrations to within the surgically castrate range and this was accompanied by equivalent subjective and objective response rates and times to treatment failure. At a median follow-up of 2 years there was no difference in overall survival, confirming that Zoladex is an effective medical alternative to orchiectomy in patients with metastatic disease.

Topics: Aged; Aged, 80 and over; Buserelin; Goserelin; Humans; Ireland; Male; Orchiectomy; Prostatic Neoplasms; Survival Rate; Testosterone; United Kingdom

Twenty-one patients with stage T3 cancer of the prostate underwent complete androgen deprivation (LH-RH agonist and flutamide) for 3 months prior to radical prostatectomy. Two problems were to be dealt with: the decrease in the volume of the prostate, and the possibility of downstaging (= pT less than pT3 according to the UICC 1987 classification) of the prostatic cancer. A decrease in the volume was noted in each case. A downstaging effect (pT in comparison to T stage) was noted in 33% of the patients. The downstaging effect was noted in 75% of grade 1 tumor, in 31% of grade 2 tumors, but not in grade 3 tumors.

Topics: Aged; Buserelin; Combined Modality Therapy; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Pilot Projects; Preoperative Care; Prostatectomy; Prostatic Neoplasms; Time Factors

A prospective randomized trial was conducted to compare the effects of the nonsteroidal antiandrogen flutamide (250 mg. 3 times daily) plus the luteinizing hormone-releasing hormone analogue goserelin acetate (Zoladex) (3.6 mg. subcutaneous depot injection every 28 days) with goserelin acetate alone in advanced prostatic carcinoma. A total of 571 eligible patients, of whom 57% had distant metastases, showed no difference in subjective or objective response rates, interval to progression, treatment failure or survival after a median followup of 2 years. In the combination group more patients had an early decrease in elevated levels of tumor markers and the small number of patients with an increase in signs and symptoms within the first 4 weeks showed a significant decrease. However, increased gastrointestinal and hepatic toxicity in the combination group resulted in 44 patients being withdrawn from the trial. These results indicate that the combination of goserelin acetate with flutamide provides no long-term clinical benefit in patients with advanced prostatic carcinoma compared to goserelin acetate alone.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Delayed-Action Preparations; Drug Tolerance; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms; Remission Induction; Time Factors; United Kingdom

This study compared goserelin monotherapy with goserelin plus flutamide in the treatment of stage C or D prostatic cancer. Patients were stratified according to whether distant metastases were present or absent. After a mean follow-up of 33 months, combined treatment with goserelin and flutamide produced a higher response rate and a more rapid normalization of abnormal levels of prostatic acid phosphatase and prostatic specific antigen than treatment with goserelin alone. A more prompt relief of bone pain was also evident. An advantage, though not statistically significant, in terms of progression and survival was demonstrated in the combination group when metastases were present before the start of treatment. In both groups, the median for progression as well as the PCA-related and nonrelated death was not achieved during the study period.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Carcinoma; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Remission Induction; Survival Rate

Two hundred and fifty patients were entered into a randomized clinical study to compare the effectiveness of goserelin (Zoladex) in depot formulation with diethyl stilboestrol in locally advanced or metastatic prostate cancer. In 22 patients from the two arms of the study regular assessments were made of the effect of these hormone treatments on the haemostatic system. Selection of those patients with no recent surgical intervention and those on no drugs liable to interfere with the haemostatic mechanism was done at entry, in order to remove bias and achieve comparable groups. Baseline comparison of the two treatment groups showed no difference in clinical or biochemical measures of disease extent or activity, including serum prostate specific antigen (PSA) levels. There was a significant fall in plasma antithrombin-III (AT-III) activity in the DES treated group both from baseline and compared with the goserelin group. This effect commenced within 1 month and was maintained until monitoring ceased at 12 months. There was also a significant increase of fibrinolytic activity in the DES treated patients compared with those on goserelin. No divergence between the two treatment groups was seen in any other haematological parameters at baseline or on follow-up. A single AT-III estimation was also performed on a larger group of 74 patients at median follow-up time of 17 months (range 3-24). This confirmed the difference noted in the original study group. In the main study thrombotic episodes were noted in 13/126 patients treated with DES and 0/124 treated with goserelin (P less than 0.001). These findings suggest that lowered AT-III is the major factor through which DES affects the coagulation mechanism, and that no such effect is seen with goserelin treatment despite an equivalent therapeutic efficacy.

Topics: Aged; Aged, 80 and over; Antithrombin III; Buserelin; Diethylstilbestrol; Goserelin; Hemostasis; Humans; Male; Middle Aged; Prostatic Neoplasms

This article reviews the serial bone scans of 149 of 327 patients entered into a randomized prospective trial comparing orchidectomy versus zoladex and flutamide in patients with metastatic prostatic cancer. Attention is drawn to the difficulty of evaluating the response rate and of the importance of tumor load in determining survival. The use of sequential bone scans once the diagnosis of metastatic disease has been confirmed is of questionable value as the scans are expensive and contribute little to the further management of the patient in the absence of symptoms requiring relief.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Radionuclide Imaging; Randomized Controlled Trials as Topic; Survival Rate

Very often not enough patients are entered and/or the follow-up is insufficient to be able to draw valid conclusions in cancer clinical trials. In this article, we discuss the possibility of pooling the data from two or more trials asking the same or similar questions in order to overcome such problems. How comparable the studies should be for combining their data, in terms of design, patient population, follow-up, and end-points, is discussed in the first part of this paper. Whether these general considerations were completely or partially fulfilled in the two prostatic studies of the EORTC and DAPROCA is the subject of the second part of this article. Problems of interpreting apparently contradictory results, like the superiority of zoladex and flutamide over orchidectomy in terms of time to progression with no clear superiority in terms of overall duration of survival, is also discussed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Flutamide; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate

A total of 327 patients with metastatic prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex depot supplemented by flutamide 250 mg 3 qid. Statistically significant increases in time to subjective and objective progression were recorded in favor of the combination treatment. No differences in time to death by cancer or overall death were recorded. The clinical significance of these differences will be reassessed once additional follow-up is available and further analysis of the overall clinical material has been carried out.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Flutamide; Goserelin; Humans; Male; Middle Aged; Multicenter Studies as Topic; Orchiectomy; Prognosis; Prostatic Neoplasms; Radionuclide Imaging; Randomized Controlled Trials as Topic; Survival Rate

In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor of the combination therapy, whereas no statistically significant difference was found in subjective response to therapy, time to progression, and overall survival. Adverse effects were more commonly encountered in the pharmacologically treated patients. It is concluded that the combination of zoladex plus flutamide is not clinically superior to orchiectomy in the treatment of patients with advanced carcinoma of the prostate.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate

A total of 591 patients with advanced prostatic cancer have been randomized to either orchiectomy or treatment with zoladex 3.6 mg as a depot preparation combined with flutamide 250 mg tid in two European studies, EORTC protocol 30853 and DAPROCA 86. Identical design and comparable patient characteristics in the two studies have allowed combined analysis. A small but statistically significant difference in time to objective progression or death from prostatic cancer was found in favor of the combination treatment. However, time from objective progression to death was longer in the group initially allocated to orchiectomy. Thus, no difference between treatment groups in overall survival was found. As a conclusion, the combined androgen blockade was not superior to orchiectomy in the treatment of patients with advanced prostatic cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Buserelin; Flutamide; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate

Topics: Aged; Anilides; Buserelin; Combined Modality Therapy; Europe; Flutamide; Goserelin; Humans; Male; Middle Aged; Multicenter Studies as Topic; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate

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

Twelve patients with advanced prostatic carcinoma and relapse following previous hormone manipulation therapy were treated with Zoladex-depot every 4 weeks. The treatment was well tolerated and the endocrine response was satisfactory. However, no clinically important improvement was obtained.

Topics: Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Prostatic Neoplasms; Remission Induction

In patients with locally advanced (bulky) carcinoma of the prostate, definitive radiotherapy is associated with a high rate of local recurrence. The Radiation Therapy Oncology Group (RTOG) has conducted several studies evaluating hormonal cytoreduction (used as an induction regimen) as a means of improving the local control rate. RTOG 85-19 tested an induction regimen consisting of a depot LH-RH agonist (Zoladex) and an antiandrogen (flutamide). Eligible patients were those with bulky primary lesions (stage B2 and C) with disease confined to the pelvis. Zoladex was administered every 29 days via a subcutaneous injection. Flutamide was given by mouth in a dose of 250 mg t.i.d. Administration of the drugs was initiated 2 months prior to start of radiotherapy and was terminated at completion of the radiotherapy course. Radiotherapy consisted of 180-200 rad/day, 4,400-4,500 rad to the regional lymphatics, and 6,500-7,000 rad to the prostate. The primary aim of the study was to evaluate the effectiveness and toxicity of the combined (hormonal cytoreduction plus definitive radiotherapy) regimen. Thirty-one patients were accessioned; 30 are analyzable. The drug-related toxicity appears acceptable. It included appearance of diarrhea before initiation of radiotherapy in two patients, nausea during the 2nd week of drug administration in two patients, and skin rash in three patients. These phenomena appear to be related to flutamide. Hot flashes were recorded in 17 patients. With a minimum follow-up of 2 years, clearance of the primary lesions (by clinical examination) was documented in 28 of 30 patients. During the 1st year, two of 30 patients died (of unrelated causes) with residual palpable tumors. The observed toxicity appears acceptable and the response rate encouraging. A phase III study comparing the tested regimen against radiotherapy alone appears warranted.

Topics: Buserelin; Diarrhea; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms; Radiotherapy

A total of 327 patients with metastatic prostate cancer have been randomized to either orchidectomy or treatment with goserelin (Zoladez) 3.6 mg depot preparation combined with flutamide (Eulexin) 250 mg t.i.d. in a phase III study (EORTC 30853). A small but statistically significant difference in time to subjective and objective progression of disease was found in favour of the combination treatment. However, time from objective progression to death was longer in the group initially allocated to orchidectomy. Thus no difference was found in overall survival between the two treatment groups. The clinical significance of these differences requires further follow up and analysis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Drug Combinations; Drug Evaluation; Europe; Flutamide; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Risk Factors

Topics: Aged; Antineoplastic Agents; Buserelin; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; Male; Prostatic Neoplasms

Topics: Buserelin; Clinical Trials as Topic; Flutamide; Goserelin; Humans; Job Description; Male; Nursing Staff, Hospital; Prostatic Neoplasms

A new longer-acting depot formulation containing 10.8 mg Zoladex was administered subcutaneously without anesthetic to 35 patients with advanced carcinoma of the prostate. Pharmacodynamic and pharmacokinetic data show that following a transient elevation in serum LH and testosterone, the levels of both hormones decrease. Serum testosterone reaches the castrate range in all patients by week 4 and remains at this level for at least 12 weeks. The serum Zoladex profile shows that castrate serum testosterone values can be sustained by very low serum concentrations of the drug of around 0.05 ng/ml. In this preliminary report, the efficacy and safety of this new longer-acting 3-month depot formulation of 10.8 mg Zoladex has been shown to be comparable to the 1-month depot formulation of 3.6 mg Zoladex, in patients with advanced carcinoma of the prostate.

Topics: Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Drug Evaluation; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone

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

Topics: Buserelin; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms

Treatment with bilateral orchidectomy was compared with Zoladex, 3.6 mg depot, plus flutamide, 250 mg t.i.d., in a randomized prospective study by the European Organization for Research and Treatment of Cancer (EORTC). Small but statistically significant differences in time to subjective and objective progression of disease were found in favor of Zoladex plus flutamide. However, time from objective progression to death was longer in the orchidectomy group. The clinical significance of these differences requires further follow-up and analysis. No difference was found in overall survival between the 2 treatment groups.

Topics: Aged; Alanine Transaminase; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Carcinoma; Combined Modality Therapy; Flutamide; Follow-Up Studies; Goserelin; Humans; Liver Function Tests; Male; Orchiectomy; Prospective Studies; Prostatic Neoplasms; Survival Rate

The study comprised 262 patients with previously untreated advanced carcinoma of the prostate. Patients were randomized either to undergo orchidectomy or to receive combined treatment with Zoladex, 3.6 mg every 4 weeks, plus flutamide, 250 mg t.i.d. At present the median follow-up is 39 months. The objective response to therapy was better in the Zoladex plus flutamide group, but no differences in subjective response, time to disease progression, or survival have been demonstrated between the 2 groups. Adverse effects were more common in the Zoladex plus flutamide group. Thus, 'total androgen blockade' with Zoladex plus flutamide was not clinically superior to orchidectomy in the treatment of patients with advanced prostatic cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Combined Modality Therapy; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Survival Rate

A double-blind, placebo-controlled, randomized, multicenter study was undertaken to investigate the effects of Zoladex plus flutamide vs. Zoladex plus placebo in patients with advanced prostatic cancer. Interim analysis has revealed no differences between the 2 groups in objective or subjective responses at 6 months' follow-up or in overall survival and time to disease progression at 15 months' follow-up.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Double-Blind Method; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Survival Rate

Since March 1987, 304 evaluable patients with stage C and D prostate cancer have been entered into a prospective trial comparing Zoladex and Zoladex plus flutamide. To date, there has been no significant difference in over-all and progression-free survival between the 2 treatment groups. However, combined treatment produced a higher response rate (particularly in stage D patients) and a more rapid normalization of abnormal prostatic acid phosphatase levels. In addition, more prompt relief of bone pain was evident in the Zoladex plus flutamide group. However, significantly more side-effects were associated with combined treatment. These findings should be considered with caution because they form an interim analysis, and follow-up time is short. The results do suggest, however, that there is no particular advantage in using a combination of Zoladex plus flutamide compared to adding flutamide on failure of treatment with Zoladex alone.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Neoplasm Staging; Prostatic Neoplasms; Survival Rate

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 identification of the decapeptide luteinizing hormone-releasing hormone (LHRH) has led to the development of LHRH agonists, which are a new class of drugs for the treatment of advanced prostate cancer. These peptides have a modified amino acid structure that makes them more potent than LHRH. Prolonged administration of LHRH agonists results in down-regulation of the LHRH receptors in the pituitary and decreased secretion of luteinizing hormone. The result is decreased production of testosterone by Leydig cells, which is the basis for the use of LHRH agonists to treat prostate cancer. The effectiveness of LHRH agonists has been demonstrated in the United States in several randomized, controlled clinical trials. Daily administration of leuprolide produced equivalent results compared with diethylstilbestrol (DES). More recently, in two separate, randomized studies, the long-acting LHRH agonist Zoladex (ICI Pharma, Wilmington, Delaware) produced the same objective response rate as DES or bilateral orchiectomy. The equivalent response rates obtained with LHRH agonists indicate that these drugs can now be considered a reasonable treatment option for patients with metastatic prostatic cancer.

Topics: Antineoplastic Agents; Buserelin; Clinical Trials as Topic; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms

Two multicenter, open, randomized phase III clinical trials were conducted in the United Kingdom to compare the effectiveness and safety of the depot formulation of the luteinizing hormone-releasing hormone (LHRH) agonist goserelin (Zoladex, ICI Pharma, Wilmington, Delaware), 3.6 mg sc/28 d, with orchiectomy and with diethylstilbestrol (DES), 1 mg tid, in the treatment of advanced prostatic cancer. In the Zoladex versus orchiectomy trial, there was no significant difference between the treatment groups with regard to subjective and objective responses (British Prostate Group criteria), endocrine responses, clinical effects and side effects, time to treatment failure and death, or survival after similar median follow-up periods. It was concluded that depot Zoladex had behaved as a truly medical alternative to orchiectomy. In the Zoladex versus DES trial, subjective and objective responses (British Prostate Group and National Prostatic Cancer Project criteria), response duration and survival were similar. However, there was a more rapid response to treatment in the depot Zoladex group. Side effects from Zoladex such as flare symptoms during the initial stages of treatment required no discontinuation of therapy; in contrast, 15 percent of patients receiving DES required cessation of therapy during the first three months because of side effects. It was concluded that depot Zoladex was superior to DES in its attainment of an early objective response and in its absence of side effects, and that Zoladex was comparable with DES in terms of response rates and survival.

Topics: Antineoplastic Agents; Buserelin; Clinical Trials as Topic; Diethylstilbestrol; Goserelin; Humans; Male; Multicenter Studies as Topic; Orchiectomy; Prostatic Neoplasms; Random Allocation; United Kingdom

Topics: Anilides; Buserelin; Clinical Trials as Topic; Europe; Flutamide; Goserelin; Humans; Male; Multicenter Studies as Topic; Orchiectomy; Prognosis; Prospective Studies; Prostatic Neoplasms; Random Allocation

The first interim report of this multicentre prospective clinical trial to compare the efficacy of 'Zoladex' versus 'Zoladex' + flutamide in the treatment of advanced carcinoma of the prostate furnishes evidence of a reduction of the incidence of tumour flare within the first 4 weeks of therapy. The combination of 'Zoladex' and flutamide produced an earlier response in tumour markers (TAP, PAP) only. The combination, however, had no effect on subjective and objective response rates and had a negative effect on time to treatment failure. Flutamide produces a significant increase in toxicity and withdrawals due to toxicity. This interim analysis indicates that the continued administration of flutamide in combination with 'Zoladex' has no significant clinical benefit over that of 'Zoladex' alone. Further follow-up is required to determine whether combination treatment has any effect on time to treatment failure and survival.

Topics: Aged; Anilides; Buserelin; Clinical Trials as Topic; Drug Therapy, Combination; Flutamide; Goserelin; Humans; International Cooperation; Male; Multicenter Studies as Topic; Prognosis; Prostatic Neoplasms; Random Allocation

Topics: Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Goserelin; Humans; Male; Multicenter Studies as Topic; Orchiectomy; Prostatic Neoplasms; Random Allocation; United Kingdom

Topics: Aged; Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Diethylstilbestrol; Goserelin; Humans; Male; Multicenter Studies as Topic; Prostatic Neoplasms; Random Allocation; United Kingdom

An LHRH agonist, Zoladex, was employed as a monthly depot in 56 previously untreated patients with advanced carcinoma of the prostate. Of 53 evaluable patients, 27 achieved partial remission and 7 were stable. Median duration of response was 10 months. A favorable subjective response was attained in 68% of the patients. During treatment, serum testosterone was in the castrate range in all patients except five. Possible explanations for this escape phenomenon are discussed. No toxicity was observed and treatment was well tolerated in all patients. Thirty-two patients underwent bilateral orchiectomy following treatment failure of Zoladex. In one patient partial remission according to protocol criteria was recorded. Treatment with LHRH agonists seems safe and may serve as an alternative to conventional hormonal treatment of advanced carcinoma of the prostate.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Buserelin; Carcinoma; Combined Modality Therapy; Delayed-Action Preparations; Goserelin; Humans; Male; Middle Aged; Multicenter Studies as Topic; Orchiectomy; Prostatic Neoplasms

Topics: Androgen Antagonists; Buserelin; Clinical Trials as Topic; Diethylstilbestrol; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms

Topics: Buserelin; Clinical Trials as Topic; Europe; Flutamide; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Quality of Life; Surveys and Questionnaires

Topics: Aged; Aged, 80 and over; Buserelin; Carcinoma; Clinical Trials as Topic; Drug Administration Schedule; Goserelin; Humans; Male; Middle Aged; Netherlands; Prostatic Neoplasms; Testosterone

Topics: Aged; Aged, 80 and over; Buserelin; Carcinoma; Clinical Trials as Topic; Combined Modality Therapy; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prospective Studies; Prostatic Neoplasms; Random Allocation

To investigate the clinical efficacy, safety and endocrinology of ICI 118630 (Zoladex) depot formulation at 3 different dose levels (0.9, 1.8 and 3.6 mg), 90 patients were randomized to receive either one of the 3 doses from April, 1985 to March, 1986 in 28 centers. The depot preparation was injected subcutaneously every 4 weeks 3 times (for up to 12 weeks). Clinical efficacy was evaluated in terms of tumor response and overall subjective response. In 70 patients eligible for tumor response evaluation, 14 out of 22 (63.6%) in the 0.9 mg group, 11 out of 23 (47.8%) in the 1.8 mg group, and 17 out of 25 (68.0%) in the 3.6 mg group showed clinical improvement, that is, either complete response or partial response. In 72 eligible patients for overall subjective response evaluation, clinical subjective improvement was observed in 75.0, 81.8 and 88.0% of the patients in the 3 groups, respectively. There was no significant difference between the groups. As for endocrinology, there were 75 eligible patients. Endocrinological effect was observed in 23 out of 25 (92.0%) in the 0.9 mg group, 100% in both 1.8 mg and 3.6 mg groups. There was no significant difference between the groups. Castration was achieved by week 3.5 +/- 1.7 of therapy on average and by week 2 in the earliest case. There was no significant difference in incidence of side effects between the 3 groups: 5 out of 26 (19.2%) in the 0.9 mg group, 8 out of 29 (27.6%) in the 1.8 mg group, and 2 out of 30 (6.7%) in the 3.6 mg group. Flares presented as an increase in bone pain in 2 and as ureteric obstruction in 2 all in the 1.8 mg group but none in the other 2 dose groups. These flares disappeared on further treatment with Zoladex. These patients showed a clinical-response. The blood level of Zoladex was dose dependent, reaching its peak at week 2 of therapy in all 3 dose groups. There was no evidence of accumulation. Since these results demonstrate that 3.6 mg produces medical castration earlier, it may well be considered as an optimal dose in men.

Topics: Buserelin; Delayed-Action Preparations; Drug Evaluation; Goserelin; Humans; Male; Prostatic Neoplasms

The effects of long term GnRH treatment with the biodegradable depot formulation of ICI 118.630 on hormone levels and spermatogenesis were investigated in 18 males with advanced prostate cancer. Plasma levels of FSH, LH, testosterone, DHEA-S and SHBG were monitored at regular intervals. The drug suppressed FSH, LH and testosterone significantly and did not affect DHEA-S and SHBG plasma levels. Tissue specimens for histologic assessment and quantitative analysis of germinal cell types were obtained at secondary orchidectomy in 16 patients immediately following GnRH analogue treatment. Germinal cell maturation was arrested at the spermatogonial stage. In two patients discontinuing treatment histologic assessment of secondary orchidectomy specimens 9 and 10 months after the last GnRH analogue depot injection resulted in germinal cell maturation to late spermatids in part of the tubule cross sections. These results indicate that long term administration of the GnRH analogue fails to produce complete testicular sclerosis and spermatogenic arrest might be reversible.

Topics: Aged; Aged, 80 and over; Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Goserelin; Hormones; Humans; Male; Middle Aged; Prostatic Neoplasms; Spermatogenesis; Time Factors

Topics: Adenocarcinoma; Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Interleukin-2; Male; Orchiectomy; Prostatic Neoplasms; Random Allocation; Recombinant Proteins

In order to evaluate the proposed benefit of complete androgen blockade in the treatment of patients with advanced prostatic cancer, we initiated a multicenter prospective and randomized study. At the time of this report 99 patients with newly diagnosed, previously untreated prostatic cancer were randomly distributed to one of the following treatments: group I, orchiectomy plus antiandrogen Flutamide; group II, depot LH-RH analog Zoladex plus Flutamide; group III, orchiectomy alone, and group IV, Zoladex alone. Our preliminary data fail to demonstrate a superiority of total androgen blockade over partial androgen blockade in the treatment of patients with advanced cancer of the prostate.

Topics: Androgen Antagonists; Androgens; Buserelin; Flutamide; Goserelin; Humans; Male; Multicenter Studies as Topic; Orchiectomy; Prospective Studies; Prostatic Neoplasms; Random Allocation

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

The Zoladex (ICI 118,630) multicenter trial included 149 patients with stage B +o D prostatic cancer recruited from 1984 to date. Of them 53 clinical responders on the treatment for 40 weeks or longer were subjected to assessment of antitumour response, overall subjective response, endocrinological response, safety and usefulness. The responders consistently showed a clinical response as evidenced by antitumour response in 32 of 50 patients (64.0%) at week 12 and in 35 of 51 (68.6%) at week 40, and overall subjective response in 42 out of 47 patients (89.4%) at both week 12 and week 40. Endocrinologically, all of the 47 eligible patients maintained a 40-week or longer response. Adverse reactions were observed in 19 out of 73 patients (26.0%), subdivided by the time of occurrence as 15/73 (20.5%) up to week 12, 3/71 (4.6%) between week 12 and week 40, and 5/53 (9.4%) in and after week 40. No patient required the discontinuance of treatment. Usefulness of the drug was observed in 51 out of 52 patients (98.1%). The results indicated that Zoladex in a once monthly regimen may be of great advantage to elderly patients with prostatic cancer, and allow an improved patient compliance: Zoladex may not only produce clinical remission but also improve the quality of life.

Topics: Buserelin; Drug Evaluation; Goserelin; Humans; Male; Multicenter Studies as Topic; Prostatic Neoplasms; Remission Induction; Time Factors

Ninety patients with advanced prostatic cancer (15 with stage B, 23 with stage C, and 52 with stage D) were randomized to receive 0.9, 1.8, or 3.6 mg, respectively, of Zoladex depot subcutaneous injection every 28 days for 12 weeks. The serum levels of LH, FSH, and testosterone were elevated after the first injection, and followed by a significant decrease. The suppression of testosterone levels in the blood to castrate levels was observed in all patients except two treated with 0.9 mg. Objective response (CR and PR) was seen in 63.6% (0.9 mg), 47.8% (1.8 mg), and 68% (3.6 mg) of patients according to the Japanese Prostatic Group Criteria. Subjective improvement (performance status, analgesic consumption) was also observed in 75-88% of patients but without a statistically significant difference between each dose group. Only minor adverse effects were found during the treatments. The drug was detected dose dependently in the blood by radioimmunoassay. These results suggest that endocrine therapy with Zoladex depot in doses of 3.6 mg subcutaneously every 4 weeks is a useful alternative to surgical castration in patients with prostatic cancer.

Topics: Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Follicle Stimulating Hormone; Goserelin; Humans; Injections, Subcutaneous; Japan; Luteinizing Hormone; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Random Allocation; Remission Induction; Testosterone

From April 1984 to May 1986, 129 patients with prostate cancer entered a prospective trial with a new LH-RH agonist, Zoladex. Mean age was 72 years (range of 45-94 years) and, in most cases, patients had metastatic disease, not previously treated by chemotherapy or hormone therapy. Patients received a monthly injection of 3.6 mg. Serum testosterone was lowered into the range of castrate levels after 4 weeks of treatment. In 105 evaluable patients at 3 months, a 65% partial response (PR) rate was observed, with 11% stable and 24% progressive disease. Median time to progression was 37 weeks. Analysis of objective criteria revealed 30% PR for prostate volume and 51% CR-PR for prostatic acid phosphatases. Seventeen percent of lytic metastases had recalcified. One hundred twenty-nine patients were evaluable for toxicity. Endocrinological side effects were common: decrease in libido, 92%; impotence, 86%; hot flushes, 48%; and breast swelling or tenderness, 9%. Nonendocrinologic side effects were rare. The treatment is generally well accepted by patients owing to the convenient depot formulation and to the minor side effects.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Follicle Stimulating Hormone; France; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prospective Studies; Prostate; Prostatic Neoplasms

A randomized, controlled trial of the treatment of metastatic prostatic cancer using either the LH-RH analogue Zoladex or orchidectomy is reported. The trial was conducted in the U.K. and Ireland and involved participants in 17 centers. The design of the trial is outlined and the response criteria discussed. The results show that the patient characteristics in the two treatment groups were comparable upon entry. Repeated administration of Zoladex every 28 days has been shown to be as effective as orchidectomy in lowering serum testosterone to castrate levels. The subjective and objective response rates were similar, as were the duration of response, time to treatment failure, and survival rates. The withdrawals from the trial and adverse reactions are discussed. These results, 10 months after the closure of recruitment to the trial, seem to indicate that Zoladex and orchidectomy are equivalent treatments and that Zoladex seems to be a truly medical alternative to surgical castration. Finally, other ongoing U.K. trials of the treatment of advanced prostate cancer are outlined.

Topics: Aged; Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Male; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Remission Induction; Testosterone; United Kingdom

A study comparing Zoladex 3.6 mg depot with diethylstilbestrol (DES) 3 mg/day was initiated in August 1985. One hundred ninety-three patients with histologically confirmed prostate cancer T3/4 or M1 have been randomized up to 31 March 1987: 95 to Zoladex, 98 to DES. No patient had received prior systemic therapy. There is no bias in the treatment groups in terms of baseline characteristics. Median follow-up is 11 months, and the response rate at 12 months from randomization (CR + PR) for Zoladex is 70 +/- 9.4% and 50 +/- 10.1% for DES. Median time to best response is 6 months for Zoladex and 12 months for DES (using the Kaplan-Meier life table method). Subjective responses are 56 +/- 10.2% for Zoladex and 44 +/- 10% for DES. Five increases in bone pain were found after the first Zoladex treatment, as well as one increased ureteric obstruction. None required treatment withdrawal. Seventeen patients on DES were withdrawn due to adverse reaction (chi 2 = 4.33, 1df, p less than 0.05). Overall survival at 31 March 1987 is 84% for the Zoladex group and 78% for the DES group. This study has shown that Zoladex is superior to DES in achieving early tumor response in advanced prostate cancer, without causing serious complications warranting withdrawal of treatment.

Topics: Buserelin; Delayed-Action Preparations; Diethylstilbestrol; England; Follow-Up Studies; Goserelin; Humans; Male; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Random Allocation; Remission Induction; Testosterone

A multicenter randomized clinical trial was carried out between May, 1986 and May, 1987 involving 82 patients with stage B-D prostatic carcinoma from 29 centers. The clinical efficacy, endocrine effect, safety and usefulness of the luteinizing hormone-releasing hormone (LH-RH) analogue and other endocrine manipulations in the treatment of prostatic carcinoma. Zoladex depot containing 3.6 mg of ICI 118,630, an LH-RH analogue, was administered every four weeks 3 times in total. Patients in the control group received either 300 mg of diethylstilbestrol diphosphate orally daily for 12 weeks or orchidectomy. An antitumor effect (CR + PR) was observed in 21 of the 33 patients (63.6%) in the Zoladex group and in 22 of the 33 (66.7%) in the control group, showing no significant difference between the two groups. There was no significant difference in overall subjective response either; 21 of the 24 (87.5%) in the Zoladex group and 24 of the 30 (80.0%) in the control group. In both groups, 100% endocrine effect was obtained as shown by achievement of castration in all patients. Adverse reactions were observed in 14 of the 39 (35.9%) patients treated with Zoladex as compared with 19 of the 34 (55.9%) control patients, resulting in no significant difference in the incidence between the two groups. These adverse reactions were not so severe as to require withdrawal from the study. In both groups, the treatment was assessed as slightly or more useful in 29 of the 33 (87.9%) patients. From these results, it is concluded that Zoladex, 3.6 mg depot, is a useful drug for treatment of prostatic cancer, having clinical efficacy and endocrine effects comparable to those of the conventional endocrine manipulations, being safe, and causing less physiological and psychological pain.

Topics: Aged; Buserelin; Castration; Clinical Trials as Topic; Estrogens; Goserelin; Humans; Male; Middle Aged; Multicenter Studies as Topic; Prostatic Neoplasms

One hundred and thirty-nine patients with advanced prostate cancer were entered into a randomised trial to test the efficacy and tolerance of goserelin 3.6 mg depot (Zoladex) versus stilboestrol 3 mg/day. As well as the usual clinical and radiological assessments of extent of disease, we used an immunoradiometric assay of prostate specific antigen (PSA) (Hybritech Europe) and normal laboratory enzymatic assays of acid phosphatase (AP) and alkaline phosphatase (ALKP) for biochemical assessment. The upper limit of normal for PSA was taken as 10 micrograms/l. The range of PSA was wide and differed significantly from that of AP and to a lesser extent ALKP in metastatic cases. PSA outperformed both AP and ALKP in both the local and advanced groups in terms of sensitivity. There was no correlation, however, between histological grade and level of PSA, AP or ALKP (the latter in cases with bone disease). In patients with metastatic disease diagnosed by bone scan, nine patients had one abnormal site/one "hot spot", and all of these had a PSA greater than twice the normal upper limit. Early death due to prostate cancer was noted in four patients with levels of PSA greater than 2500 micrograms/l. PSA is more sensitive than either enzymatic AP or ALKP in both locally advanced and metastatic prostate cancer and is useful in identifying those advanced cases who have single lesions on bone scan. In this series PSA gave an overall sensitivity of 89%, compared with 63% for AP and 64% for ALKP in patients with metastatic disease.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Buserelin; Diethylstilbestrol; Goserelin; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Random Allocation

Twenty-seven patients with metastatic adenocarcinoma of the prostate were treated with the new luteinizing hormone-releasing hormone analog, Zoladex (ICI 118,630) for up to ninety-eight weeks. Initially, treatment was randomized between Zoladex 250 micrograms and 500 micrograms self-injected subcutaneously every day for a minimum period of twelve weeks following which a sustained-release, once-monthly depot formulation of Zoladex 3.6 mg s.c. was used. Acute rises in serum gonadotropins and testosterone during the first two days were followed by declines in hormone levels over the following three weeks. Median time to castration with 500 micrograms/day was twenty-two days compared with forty-three days with 250 micrograms/day (p = 0.06). No significant endocrinologic changes occurred during the transfer to the depot, and serum testosterone remained 95 per cent suppressed throughout the duration of the study. After three months the median daily serum Zoladex concentrations ranged between 0.47 and 0.53 ng/ml and were not significantly different among the three dosage forms. No specific correlation among serum Zoladex concentrations, endocrinologic parameters, and tumor response rates were found. Hot flashes initially, and decreased libido were the only common complaints. Zoladex was well tolerated, and no side effects required dose-modification or removal from the study. Tumor response rates up to one year appeared to be comparable to the conventional endocrine therapies. This analog in monthly depot formulation is recommended for further clinical evaluation.

Topics: Adenocarcinoma; Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Male; Prostatic Neoplasms; Random Allocation; Time Factors

Zoladex, a sustained-release luteinizing hormone--releasing hormone (LHRH) analogue administered by subcutaneous injection every 28 days, was evaluated at three dose levels in 46 men with untreated advanced prostate cancer. All three Zoladex doses yielded similar endocrinologic effects. After initial transient increases in serum luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations, serum testosterone was suppressed uniformly to castration levels within 22 days. At a median follow-up of 41 weeks, Zoladex had maintained persistent suppression of serum testosterone. Measurements of serum Zoladex levels indicated that release of the drug from the injected depot was sustained over a period of 1 month and that there was no drug accumulation as evaluated over an initial 3-month period. No antibodies to Zoladex were detected. Tumor regression rates and side effects with Zoladex therapy were similar to those reported with daily injections of subcutaneous LHRH therapy. Signs and symptoms consistent with a brief tumor flare after the first injection of the LHRH analogue were noted in eight (17%) of the study entrants. Spinal cord compression was observed in two patients within 1 week from the onset of therapy. Zoladex is considered to be an effective, sustained-release LHRH analogue for the treatment of patients with prostate cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Drug Evaluation; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Statistics as Topic; Testosterone

The interim results of the randomised, Phase III trial of Zoladex against castration in the management of patients with metastatic carcinoma of the prostate is discussed. Trials commenced in October 1984 and incorporated 359 patients when recruitment ceased in January 1986. The preliminary report concerns the first 240 patients who had a minimum of 3 months follow-up. Entry criteria included patients who had no previous treatment with the exception of first-line localised radiotherapy and those who had distant bone or soft tissue metastases. Fourteen patients were excluded on the basis of protocol violations. The objective assessment of response was based on the British Prostate Group Criteria and was performed monthly for the first 3 months and 3-monthly thereafter. Pre-treatment disease characteristics of patients in both groups were similar at entry and there were no significant differences in the subjective response data of patients between the orchidectomy (n = 106) and the Zoladex group (n = 120). Objective response rates at 12 and 24 weeks of treatment were also identical for both treatment groups. Serum testosterone concentrations were below the 'castrate' level (less than 2 nmol/L) for Zoladex group as well as the orchidectomy group up to 48 weeks. The drug was well-tolerated with minimal side effects, those resulting from testosterone withdrawal were similar in both groups. The report therefore indicates clearly that this partical formulation of LH-RH analogue provides a valuable alternative to the surgical procedure in the treatment of carcinoma of the prostate.

Topics: Buserelin; Clinical Trials as Topic; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Random Allocation; Testosterone

The introduction of potent analogues of gonadotropin hormone-releasing hormone (GnRH) into clinical practice and their use in patients with metastatic prostatic carcinoma provides an effective alternative to the exogenous administration of pharmacologic doses of estrogens or surgical castration. Their advantages over estrogens are primarily related to a lower incidence of cardiovascular toxicity and gynecomastia. Their choice over orchiectomy is based on cosmetic and psychologic factors since their endocrine effects and clinical benefits are virtually the same. In this review, we describe the current experience with GnRH analogues in the treatment of prostatic carcinoma and discuss their use in the context of other endocrine manipulations. GnRH analogues act on the pituitary and indirectly affect gonadal function, and represent an opportunity for combination with other compounds capable of suppressing or interfering with the effects of circulating and androgens. The availability of several new compounds affecting different aspects of androgen metabolism provides promise for rational drug selection and testing.

Topics: Buserelin; Clinical Trials as Topic; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Gonadotropins, Pituitary; Goserelin; Humans; Leuprolide; Male; Nafarelin; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Testosterone

Topics: Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Goserelin; Humans; Male; Prostatic Neoplasms

Seventeen patients with advanced prostatic cancer were treated with the gonadotrophin-releasing hormone analogue DSer (tBU)6 AzaGly 10 GnRH (ICI 118630), either as a constant SC infusion, or in the form of a monthly SC slowrelease depot formulation, in which case patients were randomised to receive one of three doses. Six of these patients also received a 250-microgram SC bolus of ICI 118630, for pharmacokinetic studies, before starting the infusion or the depot. Drug levels were measured using a double-antibody radioimmunoassay. In contrast to the SC infusion, which gave a smooth serum 118630 level profile, drug release from the depot preparation was not constant, levels varying in a predictable manner throughout each 28-day period, reaching a peak proportional to the dose of ICI 118630 received, between days 15 and 18 of each cycle. With all methods of administration there was an initial rise in LH, usually followed by a rise in testosterone, after which the SC infusion and the depot were both effective in reducing serum LH to basal levels and testosterone into the castrate range within 1 month. It is too early to make any assessment of clinical response; however, depot treatment was well tolerated: Four patients experienced an initial flare in bone pain, probably related to the initial rise in testosterone, and twelve patients experienced flushing; one patient with pre-existing hydronephrosis and hydroureter developed renal failure, possibly related to a tumour flare reaction. No patients have experienced cardiovascular side effects or local reaction.

Topics: Buserelin; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Prostatic Neoplasms; Radioimmunoassay; Testosterone; Time Factors

Between April, 1984 and March, 1985 in 14 centers, 33 patients with prostatic cancer of our 14 centers were randomized to subcutaneously receive either 125, 250, or 500 micrograms/day of ICI 118,630, an LH-RH analogue, for 12 weeks, and the clinical efficacy, safety and endocrinal effects of the drug by dose were examined. An objective partial response was obtained in 44.4% of the 125 micrograms-treated group, in 50.0% of the 250 micrograms-treated group, and 42.9% of the 500 micrograms-treated group, showing no significant difference between the groups. General subjective response rates in these three groups were respectively 75.0%, 62.5%, and 85.7%, not differing from each other significantly. No significant difference was observed in endocrinal effect which was seen in 58.3%, 66.7%, and 100% of 125 micrograms, 250 micrograms, and 500 micrograms groups, respectively. Medical castration was attained in 4.1 +/- 2.0 weeks on average. Adverse reactions observed included fever up to 37 degrees C in 1 of the 13 (7.3%) patients treated with 125 micrograms, and hot feeling at the injection site and flare in 1 of the 8 (12.5%) patients treated with 500 micrograms, which were all mild. These patients responded to further ICI 118,630 therapy without requiring any treatment for the adverse reactions.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Buserelin; Drug Evaluation; Gonadotropins, Pituitary; Goserelin; Humans; Injections, Subcutaneous; Male; Middle Aged; Prostatic Neoplasms; Random Allocation

The luteinizing hormone releasing hormone, Zoladex, has been used in three centres, Pontefract, Antwerp and Mistelbach, to treat carcinoma of the prostate. An initial protocol using a soluble daily injection has been followed by a second study employing a monthly administered depot preparation. After an initial stimulation it has been shown that both daily and monthly injections reduce plasma testosterone to castrate levels. Circulating luteinizing hormone levels are also initially stimulated and then suppressed. Treatment toxicity has been minimal and in these short term studies reduction of acid phosphatase and subjective and objective tumour responses have been similar to those expected from effective hormonal therapy of prostatic cancer.

Topics: Buserelin; Carcinoma; Clinical Trials as Topic; Delayed-Action Preparations; Drug Administration Schedule; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone; Time Factors

Twenty two patients with advanced carcinoma of the prostate have been treated for up to 3 months with the slow-release (depot) formulation of the luteinizing hormone-releasing hormone (LHRH) agonist ICI 118630. Patients were randomized to receive one of three different doses of ICI 118630 of 0.9, 1.8 or 3.6 mg. The depot preparation was injected subcutaneously every 4 weeks. At the highest dose, the concentration of testosterone in serum was significantly reduced to castrate values after 2-3 weeks of therapy. The smaller doses of ICI 118630 (1.8 or 0.9 mg every 4 weeks) similarly reduced serum testosterone concentrations although, at the lowest dose, testosterone values were not suppressed in all patients during the first month. Hormonal changes were accompanied by subjective clinical improvement in symptomatic patients and there were no significant side effects. The data clearly demonstrate the considerable therapeutic potential of ICI 118630 in the depot formulation for the treatment of advanced carcinoma of the prostate.

Topics: Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Goserelin; Humans; Luteinizing Hormone; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Testosterone

8 patients with advanced prostatic carcinoma were treated with the luteinising-hormone releasing-hormone agonist, ICI 118630, for up to 3 months. Patients received subcutaneous injections of ICI 118630 (either 100 micrograms or 250 micrograms daily). At the higher dose level, plasma testosterone concentrations were significantly reduced by day 14 and approximated to those previously recorded in castrated or diethylstilboestrol-treated patients. Plasma concentrations of luteinising hormone and follicle-stimulating hormone were similarly reduced. Reduction in the dose, to 100 micrograms/day, similarly reduced plasma testosterone. ICI 118630 shows considerable potential for the management of patients with advanced carcinoma of the prostate.

Topics: Acid Phosphatase; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Subcutaneous; Male; Prostatic Neoplasms; Testosterone

Fifteen patients with advanced carcinoma of the prostate were treated with a luteinising hormone releasing hormone agonist ICI 118 630. Three of 5 patients who had failed conventional hormone therapy have had a marked alleviation of bone pain, though no objective evidence of disease regression. Nine of 10 patients previously untreated have shown objective evidence of disease response. This drug appears to have advantages over conventional hormone therapy.

Topics: Aged; Clinical Trials as Topic; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone

To investigate interstitial lung disease (ILD) in men with prostate cancer receiving hormone therapy.. We gathered cases diagnosed with prostate cancer based on the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database from 2004 to 2020. We divided the included cases into 3 groups based on the primary suspected drugs: a hormone therapy group, a positive control group (taxanes), and a negative control group. We employed reporting odds ratio, a disproportionality method, to detect the association between ILD events and target drugs.. We finally included a total of 85 403 cases, 69 894 cases (628 ILD event cases) in the hormone therapy group, 2302 cases (158 ILD event cases) in the positive control group and 13 207 cases (72 ILD event cases) in the negative control group. There were 394 ILD event cases (62.74%) in the hormone therapy group in Japan; 78.68% of the ILD events occurred within the first year after hormone treatment. Disproportionality analysis indicated that ILD events were significantly associated with nilutamide, flutamide, bicalutamide, goserelin, degarelix and apalutamide; the reporting odds ratios (95% confidence interval) were 32.14 (11.03-93.63), 9.93 (3.62-27.21), 8.19 (6.01-11.16), 3.74 (2.61-5.37), 2.41 (1.55-3.75) and 1.94 (1.01-3.75), respectively.. Based on this FAERS pharmacovigilance analysis, the association between ILD events and hormone therapy drugs, including bicalutamide, flutamide, nilutamide, goserelin, degarelix and apalutamide, should not be ignored, especially in the Japanese population. Lung function of prostate cancer patients should be monitored when receiving the hormone therapy drugs mentioned above, especially for the first year post medication.

Topics: Adverse Drug Reaction Reporting Systems; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Goserelin; Humans; Lung Diseases, Interstitial; Male; Prostatic Neoplasms; United States; United States Food and Drug Administration

GnRH agonists and GnRH antagonists are two of the mainstays of hormonal therapy (HT) for prostate cancer (PCa). These drugs are at increased risk of cardiovascular (CV) adverse events (AEs). Aim of our study was to compare real-life data on AEs associated with GnRH agonists and GnRH antagonists based on Eudra-Vigilance (EV) and Food and Drug Administration (FDA) reported AEs.. EV and FDA databases were queried and the number of CV adverse events (AEs) for degarelix, buserelin, goserelin, leuprorelin, triptorelin until September 2021 were recorded. Specific CV AEs were recorded and data were analyzed per age and severity. pooled relative risk (PRR) was used to compare data between drugs.. CV events were reported in 315/5128 (6%) for Degarelix, in 55/628 for Buserelin (9%), in 843/12,145 (7%) for Goserelin, in 3395/71,160 (5%) for Leuprorelin and in 214/4969 (5%) for Triptorelin. In terms of specific CV disorders, Degarelix presented lower risk of hypertension (PRR 0.60 (95% CI 0.37-0.98), p = 0.04), of myocardial infarction (PRR 0.05 (95% CI 0.01-0.39), p < 0.01) and thrombosis (PRR 0.14 (0.02-1.07), p = 0.06) when compared to GnRH agonists. Overall, younger patients (<65 years) presented a very low risk of CV AEs. Side effects were classified as serious in 90-96% of the cases. Fatal AEs were 5-20% over the CV AEs and 0.2-1% over the total AEs.. Real-life data are consistent with registry studies regarding side effects related to HT. Real-life data suggest GnRH agonists are associated with higher CV AEs when compared to GnRH antagonists. Clinicians should consider these data when prescribing HT especially in patients with CV comorbidities.

Topics: Androgen Antagonists; Buserelin; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Triptorelin Pamoate; United States; United States Food and Drug Administration

In this study, we aimed to compare changes in cavernosal tissues in rats with antiandrogen treatment and orchiectomy. A total of 42 Wistar albino rats were divided into four groups. Group I, control group, Group II, LH-RH was given for 1 month, Group III-LH-RH + Bicalutamide was given for 1 month, and Group IV was defined as orchiectomy and followed up for 1 month. Measurements of intracavernosal pressure with different electrical stimuli and pathological findings of smooth muscle collagen in cavernosal tissues were examined. While the cavernosal pressure response in all the different electrical stimuli given in the control group and in all other groups was significantly lower than that in the other groups, it was statistically significant at 7.5 and 10 V (p = .005, p < 0001). According to the pathologic evaluation, the density of tissue collagen increased significantly in the other groups according to the control group. In groups 3 and 4, the density of 4+ collagen was found to be increased according to Groups 1 and 2. In the LH-RH alone group, it appears that there are no 4+ colloid density and less damage. According to these findings, the negative effect of LH-RH treatment on cavernosal tissues appears to be less.

Topics: Administration, Oral; Androgen Antagonists; Anilides; Animals; Antineoplastic Combined Chemotherapy Protocols; Collagen; Disease Models, Animal; Erectile Dysfunction; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Muscle, Smooth; Nitriles; Orchiectomy; Penis; Prostatic Neoplasms; Rats; Rats, Wistar; Tosyl Compounds

Androgen deprivation therapy (ADT) is widely used in the treatment of testosterone-dependent prostate carcinomas. ADT often increases plasma LDL and HDL cholesterol and triglycerides. The aim was to test whether ADT changes the transfer of lipids to HDL, an important aspect of this metabolism and HDL protective functions, and related parameters.. Sixteen volunteers with advanced prostate carcinoma submitted to pharmacological ADT or orchiectomy had plasma collected shortly before and after 6 months of ADT. In vitro transfer of lipids to HDL was performed by incubating plasma with donor emulsion containing radioactive lipids by 1 h at 37 °C. After chemical precipitation of apolipoprotein B-containing lipoprotein, the radioactivity of HDL fraction was counted.. ADT reduced testosterone to nearly undetectable levels and markedly diminished PSA. ADT increased the body weight but glycemia, triglycerides, LDL and HDL cholesterol, HDL lipid composition and CETP concentration were unchanged. However, ADT increased the plasma unesterified cholesterol concentration (48 ± 12 vs 56 ± 12 mg/dL, p = 0.019) and LCAT concentration (7.15 ± 1.81 vs 8.01 ± 1.55μg/mL, p = 0.020). Transfer of unesterified (7.32 ± 1.09 vs 8.18 ± 1.52%, p < 0.05) and esterified cholesterol (6.15 ± 0.69 vs 6.94 ± 1.29%, p < 0.01) and of triglycerides (6.37 ± 0.43 vs 7.18 ± 0.91%, p < 0.001) to HDL were increased after ADT. Phospholipid transfer was unchanged.. Increase in transfer of unesterified and esterified cholesterol protects against cardiovascular disease, as shown previously, and increased LCAT favors cholesterol esterification and facilitates the reverse cholesterol transport. Thus, our results suggest that ADT may offer anti-atherosclerosis protection by improving HDL functional properties. This could counteract, at least partially, the eventual worse effects on plasma lipids.

Topics: Aged; Antineoplastic Agents, Hormonal; Atherosclerosis; Cholesterol; Cholesterol Esters; Goserelin; Humans; Kallikreins; Lipids; Lipoproteins, HDL; Male; Middle Aged; Orchiectomy; Phospholipids; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Triglycerides

We report the failure to achieve castrate level of serum testosterone during luteinizing hormone-releasing hormone agonist therapy in a patient with prostate cancer. A 76-year-old man was admitted to our hospital for evaluation of an elevated serum prostate specific antigen (PSA) level (191.10 ng/ml) in August 2011. He was diagnosed with T3aN0M1b prostate adenocarcinoma. A combined androgen blockade using luteinizing hormone-releasing hormone agonist (the 1-month depot of leuprorelin acetate) and antiandrogen was administered. Due to liver dysfunction, antiandrogens, both bicalutamide and flutamide, were stopped. The 1-month depot was switched to the 3-month depot in May 2013, but the patient complained of induration and abscess at the infection site. Leuprorelin acetate was replaced by goserelin acetate. Because no adverse event appeared after injection of the 1-month depot of goserelin acetate, the 3-month depot was administered in October 2013. The PSA level increased gradually, and the testosterone level was greater than 50 ng/dl, that is, above castrate range. The 3-month depot of both leuprorelin acetate and goserelin acetate was not effective for this patient. For this reason, the 1-month depot of leuprorelin acetate was started resulting in a rapid decrease in PSA and testosterone levels. Thereafter, androgen depriving therapy could be continued. Androgen deprivation therapy is the standard treatment for patients with advanced prostate cancer and luteinizing hormone-releasing hormone aims to suppress serum testosterone to castrate range. We recommend assessing the serum testosterone levels during luteinizing hormone-releasing hormone agonist therapy for monitoring treatment efficacy and verifying progression when the PSA level increases.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Gonadotropin-Releasing Hormone; Goserelin; Humans; Kallikreins; Leuprolide; Male; Nitriles; Phenylthiohydantoin; Prostate-Specific Antigen; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Testosterone; Tosyl Compounds

The complaints of lower urinary tract symptoms (LUTS) in cases with Prostate carcinoma (Pca) depend on coexisting benign prostate hyperplasia (BPH) or aging bladder. We aimed to investigate and compare the effect of goserelin acetate with leuprolide acetate on total prostate volume (TPV), post voiding residue (PVR), International Prostate Symptom Score (IPSS) and maximum flow rate (Qmax) reduction on cases of advanced Pca.. Patients with advanced Pca were treated with goserelin acetate (10.8 mg/3 months) or leuprolide acetate (22.5 mg/3 months) for 6 months. Changes in Prostate specific antigen (PSA), testesterone level, TPV, IPSS, PVR, and Qmax were assessed every 3 months.. Fifty-one patients analyzed in this study. Mean percent decrease in PSA and testesterone from baseline to 6th month was not significantly difference between two groups (respectively; p = 0.9, p = 0.15) but TPV was reduced by -20.2 % ± 4.8 and -15.6 % ± 1.04,  the median total IPSS score was decreased by -34.77 % ± 8.8 and -19.77 % ± 6.1, median Qmax increased by 45.34 % ± 10.16 and 23.21 % ± 6.93, median PVR decreased by -31.54 % ± 8.4 and -19.23 % ± 5.5, respectively for two groups (all parameters (p < 0.05))Conclusion. In this study, we observed that the improvement of voiding parameters goserelin acetate was beter than leuprolide acetate. Especially it was detected the superiority of goserelin acetate group on the reduction of TPV, PVR and IPSS. Oncological outcomes were not different in both groups.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Goserelin; Humans; Leuprolide; Lower Urinary Tract Symptoms; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; Tumor Burden; Urination Disorders

There is no consensus on the association between the use of androgen deprivation therapy (ADT) and the risk of developing depression. This study investigated the association between ADT use and the development of depression, outpatient psychiatric services, inpatient psychiatric services, and suicide in a homogeneous group of men with prostate cancer (PC) treated with definitive radiation therapy (RT) after controlling for multiple sources of selection bias.. This was a retrospective, observational cohort study of 39,965 veterans with PC who were treated with definitive RT and were diagnosed by the US Department of Veterans Affairs health care system between January 1, 2001, and October 31, 2015. Exposure was ADT initiation within 1 year of the PC diagnosis. The primary outcome was new development of depression. Secondary outcomes were outpatient psychiatric use, inpatient psychiatric use, and suicide.. During follow-up, 934 patients were newly diagnosed with depression, 7825 patients used outpatient psychiatric services, 358 patients used inpatient psychiatric services, and 54 patients committed suicide. In the multivariable competing risks regression model, ADT was associated with the development of depression (subdistribution hazard ratio [SHR], 1.50; 95% confidence interval [CI], 1.32-1.71; P < .001). ADT was also associated with outpatient psychiatric utilization (SHR, 1.21; 95% CI, 1.16-1.27; P < .001). Finally, ADT was not associated with inpatient psychiatric utilization or suicide.. An increase in the risk of depression and the use of outpatient psychiatric services was observed in a large cohort of men with PC who received ADT with definitive RT. These results may provide further evidence for the long-term risks of ADT for psychiatric health in the treatment of PC.

Topics: Aged; Aged, 80 and over; Ambulatory Care; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Depression; Depressive Disorder; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Hospitalization; Humans; Imidazolidines; Leuprolide; Male; Mental Health Services; Middle Aged; Nitriles; Oligopeptides; Prostatic Neoplasms; Radiotherapy; Retrospective Studies; Suicide; Tosyl Compounds

Using multiparametric magnetic resonance imaging (mpMRI), we sought to preoperatively characterize prostate cancer (PCa) in the setting of antiandrogen plus androgen deprivation therapy (AA-ADT) prior to robotic-assisted radical prostatectomy (RARP). We present our preliminary findings regarding mpMRI depiction of changes of disease staging features and lesion appearance in treated prostate.. Prior to RARP, men received 6 months of enzalutamide and goserelin. mpMRI consisting of T2 weighted, b = 2,000 diffusion weighted imaging, apparent diffusion coefficient mapping, and dynamic contrast enhancement sequences was acquired before and after neoadjuvant therapy. Custom MRI-based prostate molds were printed to directly compare mpMRI findings to H&E whole-mount pathology as part of a phase II clinical trial (NCT02430480).. Twenty men underwent imaging and RARP after a regimen of AA-ADT. Positive predictive values for post-AA-ADT mpMRI diagnosis of extraprostatic extension, seminal vesicle invasion, organ-confined disease, and biopsy-confirmed PCa lesions were 71%, 80%, 80%, and 85%, respectively. Post-treatment mpMRI correctly staged disease in 15/20 (75%) cases with 17/20 (85%) correctly identified as organ-confined or not. Of those incorrectly staged, 2 were falsely positive for higher stage features and 1 was falsely negative. Post-AA-ADT T2 weighted sequences best depicted presence of PCa lesions as compared to diffusion weighted imaging and dynamic contrast enhancement sequences.. mpMRI proved reliable in detecting lesion changes after antiandrogen therapy corresponding to PCa pathology. Therefore, mpMRI of treated prostates may be helpful for assessing men for surgical planning and staging.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Benzamides; Goserelin; Humans; Male; Middle Aged; Multiparametric Magnetic Resonance Imaging; Neoplasm Staging; Nitriles; Phenylthiohydantoin; Preoperative Period; Prostatectomy; Prostatic Neoplasms; Robotic Surgical Procedures

Topics: Acetic Acid; Animals; Antineoplastic Agents, Hormonal; Biological Availability; Delayed-Action Preparations; Drug Carriers; Drug Compounding; Drug Implants; Drug Liberation; Goserelin; Humans; Hydrogels; Hydrogen-Ion Concentration; Injections, Intramuscular; Injections, Subcutaneous; Male; Microspheres; Particle Size; Poloxamer; Polylactic Acid-Polyglycolic Acid Copolymer; Prostatic Neoplasms; Rats

To investigate the changes in testosterone levels and rates of chemical castration following androgen-deprivation therapy (ADT) with goserelin, triptorelin, and leuprolide.. We retrospectively reviewed the medical records of 125 patients with prostate cancer treated with luteinizing hormone-releasing hormone (LHRH) agonists between January 2009 and December 2015. Changes in testosterone concentration during 9 months of ADT with goserelin 11.34 mg, triptorelin 11.25 mg, and leuprolide 11.25 mg were analyzed using a mixed model. The number of patients with serum testosterone below castration levels defined as various values (<50 ng/dL, <20 ng/dL, or <10 ng/dL) at 3, 6, and 9 months were also evaluated.. Of the 125 patients, 59 received goserelin, 44 received triptorelin, and 22 received leuprolide, respectively. The lowest mean testosterone levels during 9 months of treatment were achieved in patients treated with triptorelin, followed by those treated with leuprolide, and then by those treated with goserelin (p=0.001). Significant differences in chemical castration levels were observed only at <10 ng/dL, with 54.2% of goserelin, 93.2% of triptorelin, and 86.4% of leuprolide treated patients (p<0.001).. Three LHRH agonists showed comparable efficacy for achieving castration when the castration threshold was 50 or 20 ng/dL. However, triptorelin was the most potent LHRH agonist, achieving the lowest mean testosterone levels and the highest rate of chemical castration at <10 ng/dL testosterone.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Retrospective Studies; Treatment Outcome; Triptorelin Pamoate

Topics: Adenocarcinoma; Aged, 80 and over; Anilides; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Combined Modality Therapy; Fatal Outcome; Goserelin; Humans; Lymphatic Metastasis; Male; Nitriles; Prostatic Neoplasms; Skin Neoplasms; Skin Ulcer; Tosyl Compounds; Transurethral Resection of Prostate

The contractile properties of vastus lateralis muscle fibres were examined in prostate cancer (PrCa) patients undergoing androgen deprivation therapy (ADT) and in age- and activity-matched healthy male subjects (Control). Mechanically-skinned muscle fibres were exposed to a sequence of heavily Ca

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Muscle Contraction; Muscle Fibers, Skeletal; Prostatic Neoplasms

Topics: Adenocarcinoma; Aged, 80 and over; Alopecia; Anilides; Antineoplastic Combined Chemotherapy Protocols; Atrophy; Fibrosis; Goserelin; Humans; Male; Nitriles; Prostatic Neoplasms; Scalp; Skin; Tosyl Compounds

Immunohistochemical and morphometric analysis of the microcirculatory bed in the tumor and non-tumor parenchyma of the prostate was carried out with the use of endothelial cell marker CD34 in patients treated by high-intensity focused ultrasound (HIFU). The numerical density of microvessels in the adenocarcinoma focus did not correlate with the degree of its differentiation, while high values of this parameter were associated with lower incidence of local progression after HIFU. Effective HIFU ablation led to progressive fibrosis and significant reduction of the microcirculatory bed in zones of intact non-tumor glands in control samples; an inverse relationship between the degree of reduction of the microcirculatory bed and the probability of relapse was revealed. The use of HIFU in combination with androgen deprivation was associated with a decrease in numerical density of microvessels in zones of tumor and non-tumor parenchyma in patients with relapses.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antigens, CD34; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Fibrosis; Flutamide; Follow-Up Studies; Goserelin; High-Intensity Focused Ultrasound Ablation; Humans; Male; Microcirculation; Middle Aged; Prognosis; Prostate; Prostatic Neoplasms; Treatment Outcome; Tumor Microenvironment

To evaluate the impact of androgen deprivation therapy (ADT) on prostate volume, lower urinary tract symptoms (LUTS), and LUTS-related quality of life (QOL) in patients with prostate cancer.. Patients with prostate cancer (PCa) were treated with goserelin and bicalutamide for 24 weeks. Changes in the total prostate volume (TPV), International Prostate Symptom Score (IPSS), and QOL score for urinary symptoms were assessed every 12 weeks. Of the 42 patients enrolled, 8 patients withdrew and 2 were excluded, so 32 patients were analyzed.. The median age, PSA levels, and TPV were 77.5 years, 22.0 ng/mL, and 29.5 cm. In this study, we observed that ADT significantly reduced TPV and improved LUTS in patients with PCa and moderate to severe LUTS, but increased nocturia in patients with mild LUTS.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lower Urinary Tract Symptoms; Male; Nitriles; Nocturia; Organ Size; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Severity of Illness Index; Tosyl Compounds

As androgen deprivation therapy (ADT) is increasingly being used in men with localised prostate cancer, our goal was to examine the association between ADT and the risk of cardiovascular disease (CVD).. We conducted a prospective cohort study using records of a large health-care system in California. The study included men with newly diagnosed localised prostate cancer (1998-2008) who initially underwent active surveillance (N=7637) and were followed through 2010. We examined 10 individual CVD outcomes. Cox proportional hazard models incorporated time-varying treatment variables and controlled for race/ethnicity, age, and tumour characteristics, recurrence risk, CVD medication use, and CVD risk factors.. Of the 7637 subjects, nearly 30% were exposed to ADT. In the multivariable analyses, ADT was associated with an increased risk of heart failure (adjusted HR=1.81, 95% CI 1.40-2.32) in men without preexisting CVD. Elevated risks of arrhythmia (adjusted HR=1.44, 95% CI 1.02-2.01), and conduction disorder (adjusted HR=3.11, 95% CI 1.22, 7.91) were only observed among patients with preexisting CVD.. In men with clinically localised prostate cancer who were initially under active surveillance, ADT was associated with a greater risk of heart failure in men without any preexisting CVD. We also found an increased risk of arrhythmia and conduction disorder in men with preexisting CVD. This study provides the basis for identifying high-risk men treated with ADT who might benefit from regular cardiac monitoring and lifestyle modification recommendations.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Arrhythmias, Cardiac; California; Cardiovascular Diseases; Cohort Studies; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Heart Failure; Humans; Imidazolidines; Leuprolide; Male; Middle Aged; Multivariate Analysis; Neoplasm Grading; Nitriles; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Risk Factors; Tosyl Compounds

The aim of our study was to investigate the relationship between cancer-related fatigue and clinical parameters, and the effect factors of fatigue for the prostate cancer patients. Long-term follow-up is performed using the Fatigue Symptom Inventory before treatment (A), at the end of intensity-modulated radiotherapy (B), and 3 months (C), 12 months (D), 24 months (E), 36 months (F), and 48 months (G) after the end of intensity-modulated radiotherapy. Three dimensions of fatigue are assessed during follow-up: severity, perceived interference with quality of life, and duration in the past week. In all, 97 patients with locally advanced prostate cancer were enrolled in the study. Median follow-up time was 43.9 months. The fatigue index was significantly higher in the prostate-specific antigen >20 ng/mL, Gleason score >8, the Eastern Cooperative Oncology Group scores, and the higher education. The most severe fatigue occurred at time points B and C. The score for duration of fatigue fluctuated across the time points, with significantly increased scores at time points D, E, and F.In conclusion, we show that cancer-related fatigue is the important symptom which affects the quality of life for the prostate cancer patients. For patients with locally advanced prostate cancer with a high Eastern Cooperative Oncology Group score, a Gleason score of >8 points, prostate-specific antigen levels of >20 ng/mL, and high education, attention should be paid to the interference of fatigue with quality of life, especially general level of activity, ability to concentrate, and mood, after radiotherapy combined with hormonal therapy.

Topics: Aged; Antineoplastic Agents, Hormonal; Dose-Response Relationship, Drug; Fatigue; Follow-Up Studies; Goserelin; Humans; Injections, Subcutaneous; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Prostatic Neoplasms; Quality of Life; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Retrospective Studies; Time Factors; Tomography, X-Ray Computed

Prostate cancer patients who receive androgen deprivation therapy (ADT) often experience many physical and psychological side effects. ADT may be associated with increased risk for depression, but the relationship between ADT and depression is not fully understood. This study used a longitudinal design to assess depressive symptomatology in patients receiving ADT compared with two groups of matched controls.. Participants were men initiating ADT treatment (ADT+ group; n = 61) and their matched controls: prostate cancer patients treated with radical prostatectomy (ADT- group; n = 61), and no-cancer controls (CA- group; n = 61). Depressive symptomatology was assessed using the Center for Epidemiological Studies Depression Scale at ADT initiation and again 6 months later. Differences in depressive symptomatology and rates of clinically significant depressive symptomatology were analyzed between groups at each time point and within groups over time.. Between baseline and follow-up, ADT+ participants demonstrated increased depressive symptomatology and increased rates of clinically significant depressive symptomatology (ps < 0.05). ADT+ participants also reported greater depressive symptomatology than both control groups at follow-up (ps < 0.001). Rates of clinically significant depressive symptomatology were higher in the ADT+ group than the ADT- and CA- groups at both time points (baseline: 28%, 5%, 12%; follow-up: 39%, 9%, 11%).. Findings support the hypothesis that ADT administration yields increases in depression and suggest that the mechanism behind ADT's association with depression should be explored and that prostate cancer patients treated with ADT should receive particular focus in depression screening and intervention.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antidepressive Agents; Antineoplastic Agents, Hormonal; Case-Control Studies; Chemotherapy, Adjuvant; Depression; Depressive Disorder; Goserelin; Humans; Leuprolide; Longitudinal Studies; Male; Middle Aged; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Risk Factors

To determine if androgen-deprivation therapy (ADT) is associated with excess cardiac-specific mortality (CSM) in men with prostate cancer and no cardiovascular comorbidity, coronary artery disease risk factors, or congestive heart failure (CHF) or past myocardial infarction (MI).. In all, 5077 men (median age 69.5 years) with cT1c-T3N0M0 prostate cancer were treated with brachytherapy with or without neoadjuvant ADT (median duration 4 months) between 1997 and 2006. Fine and Gray competing risks analysis evaluated the association of ADT with CSM, adjusting for age, year of brachytherapy, and ADT treatment propensity score among men in groups defined by cardiac comorbidity.. After a median follow-up of 4.8 years, no association was detected between ADT and CSM in men with no cardiac risk factors (1.08% at 5 years for ADT vs 1.27% at 5 years for no ADT, adjusted hazard ratio (AHR) 0.83; 95% confidence interval (CI), 0.39-1.78; P = 0.64; n = 2653) or in men with diabetes mellitus, hypertension, or hypercholesterolaemia (2.09% vs 1.97%, AHR 1.33; 95% CI 0.70-2.53; P = 0.39; n = 2168). However, ADT was associated with significantly increased CSM in men with CHF or MI (AHR 3.28; 95% CI 1.01-10.64; P = 0.048; n = 256). In this subgroup, the 5-year cumulative incidence of CSM was 7.01% (95% CI 2.82-13.82%) for ADT vs 2.01% (95% CI 0.38-6.45%) for no ADT.. ADT was associated with a 5% absolute excess risk of CSM at 5 years in men with CHF or prior MI, suggesting that administering ADT to 20 men in this potentially vulnerable subgroup could result in one cardiac death.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Coronary Disease; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; Risk Factors

We report potent radiosensitization of prostate cancers in vitro and in vivo using goserelin-conjugated gold nanorods. Progressive receptor-mediated internalization of conjugated nanorods over time increases the radiation interaction cross-section of cells and contributes to the effects observed in vitro. The low concentrations of gold required, the long interval between injection of nanoparticles and radiation, and the use of megavoltage radiation to generate radiosensitization in vivo foretell the possibility of eventual clinical translation of this approach.. The ability of gold nanoparticles (AuNPs) to enhance the effect of physical radiation dose on tumor cells is known. This radiosensitization effect is thought to result from an increased number of photoelectric absorption events and the increased number of electrons present in gold. The authors here sought to further increase the amount and specificity of gold accumulation in prostatic cancer cells by conjugating gold nanorods to goserelin, a synthetic luteinizing hormone releasing hormone (LHRH) analogue that would bind to the LHRH receptor overexpressed in prostate cancers. It was shown that tumour cells were more sensitive to megavoltage radiation therapy. It is hoped that there would be eventual clinical translation of this approach.

Topics: Animals; Gold; Goserelin; Humans; Male; Metal Nanoparticles; Mice; Nanotubes; Prostate; Prostatic Neoplasms; Radiation-Sensitizing Agents

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with a neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). In the present study, we used a retrospective design via propensity score matching to elucidate the clinical benefit of neoadjuvant LHRH+EMP for high-risk Pca.. The Michinoku Urological Cancer Study Group database contained data for 1,268 consecutive Pca patients treated with RP alone at 4 institutions between April 2000 and March 2011 (RP alone group). In the RP alone group, we identified 386 high-risk Pca patients. The neoadjuvant LHRH+EMP group included 274 patients with high-risk Pca treated between September 2005 and November 2013 at Hirosaki University. Neoadjuvant LHRH+EMP therapy included LHRH and EMP administration at a dose of 280 mg/day for 6 months before RP. The outcome measures were overall survival (OS) and BRFS.. The propensity score-matched analysis indicated 210 matched pairs from both groups. The 5-year BRFS rates were 90.4 and 65.8 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P < 0.0001). The 5-year OS rates were 100 and 96.1 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P = 0.110).. Although the present study was not randomized, neoadjuvant LHRH+EMP therapy followed by RP appeared to reduce the risk of biochemical recurrence. A prospective randomized study is warranted to determine the clinical implications of the neoadjuvant therapy described here.

Topics: Aged; Antineoplastic Agents, Hormonal; Estramustine; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Propensity Score; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Survival Analysis

The aim of present study was to evaluate possible side effects of androgen deprivation therapy (ADT) on voice quality by means of objective and subjective measures.. Cross-sectional.. Thirty-five male patients who had been diagnosed with prostate cancer and who had been using bicalutamide and goserelin acetate combination for at least 12 months were included in the study. Thirty healthy nonsmoker males of similar age and without any laryngeal pathology constituted the control group. Acoustic and aerodynamic voice analyses and voice handicap index-10 were applied to both groups. Maximum phonation time, fundamental frequency, jitter, shimmer, and noise-to-harmonic ratio were determined during acoustic and aerodynamic voice analyses.. Maximum phonation times were 18.86 ± 5.24 and 24.20 ± 3.59 in ADT and control groups, respectively. It was significantly higher in the control group. Fundamental frequencies were 143.73 ± 18.47 and 135.00 ± 13.18 in ADT and control groups, respectively. Jitter values were 2.72 ± 0.62 and 1.99 ± 0.27 in ADT and control groups, respectively. Shimmer values were 11.50 ± 1.81 and 10.48 ± 1.36 in ADT and control groups, respectively. Fundamental frequency, jitter, and shimmer values were significantly higher in the ADT group. Noise-to-harmonic ratio values did not differ between groups. Voice handicap index-10 result was significantly higher in the ADT group.. ADT has adverse effects on the human voice. Prospective studies with long-term follow-up of a larger cohort are required for more detailed analysis.

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Cross-Sectional Studies; Goserelin; Humans; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Tosyl Compounds; Voice Quality

Topics: Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Oligopeptides; Prostatic Neoplasms

The efficacy of skin icing to reduce the pain of goserelin injection has been reported. We investigated the optimal icing time with a frozen gel pack and its effectiveness.. Abdominal skin temperatures of 49 healthy volunteers were measured after application of the frozen gel pack for 10, 15 and 30 s, and it was decided that a 15-second icing was adequate. For 55 consecutive patients who received goserelin (10.8 mg) injection, pain was evaluated employing a visual analog scale (VAS). The first injection was administered routinely. A second injection was administered after skin icing in 27 of 55 patients who wanted to try icing. At the time of the third injection, all patient decided whether they were to receive icing or the routine method.. After icing, VAS scores decreased in 20 of 27 patients. At the third injection, 18 patients requested icing.. When a patient complains of injection pain, the icing method should be considered for pain reduction.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cold Temperature; Equipment Design; Gels; Goserelin; Humans; Hypothermia, Induced; Injections, Subcutaneous; Male; Middle Aged; Pain; Pain Measurement; Prostatic Neoplasms; Skin Temperature; Time Factors; Treatment Outcome

Topics: Androstenes; Androstenols; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Benzamides; Denosumab; Diphosphonates; Docetaxel; Drug Approval; Drugs, Investigational; Estramustine; Goserelin; Humans; Imidazoles; Male; Mitoxantrone; Nitriles; Oligopeptides; Phenylthiohydantoin; Prostatic Neoplasms; Radioisotopes; Radium; Taxoids; Tissue Extracts; United States; United States Food and Drug Administration; Zoledronic Acid

To clarify clinical predictors for a prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy and to develop a nomogram to predict the prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy in patients with advanced prostate cancer that relapsed after initial combined androgen blockade. We previously reported that combined androgen blockade with an alternative non-steroidal antiandrogen is effective for advanced prostate cancer that has relapsed after initial combined androgen blockade.. We enrolled 161 patients from 14 medical institutions with histologically confirmed prostate cancer who had been treated with combination therapy and in whom cancer progressed after first-line combined androgen blockade therapy. A nomogram for the prostate-specific antigen decrease ≥50% from baseline prostate-specific antigen in response to alternative non-steroidal antiandrogen therapy was developed based on the final logistic regression model.. Overall prostate-specific antigen decreased ≥50% in 75 of 161 patients (46.6%) in response to alternative non-steroidal antiandrogen therapy. Using five independent risk factors (initial serum level of prostate-specific antigen, hemoglobin, C-reactive protein, prostate-specific antigen nadir to second hormone therapy and Gleason sum), a nomogram was developed for the prediction of prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy. The receiver operating characteristic curve showed that the accuracy of the predicted probability was 72.5% for the model.. This predictive nomogram could predict the prostate-specific antigen decrease ≥50% in response to alternative non-steroidal antiandrogen therapy and might be of benefit to determine the sequential treatment strategy in patients with relapse after first combined androgen blockade.

Topics: Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; C-Reactive Protein; Cohort Studies; Disease Progression; Drug Administration Schedule; Goserelin; Humans; Kaplan-Meier Estimate; Leuprolide; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Nomograms; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Reproducibility of Results; Retrospective Studies; ROC Curve

Although treatment options for men with metastatic castrate-resistant prostate cancer have improved in recent years, the outlook for patients remains poor, with overall survival in the region of 2 years. Response rates with chemotherapy are modest and disease progression is usually observed within months of stopping treatment.. We present a case of a 72-year-old White man of British origin with metastatic castrate-resistant prostate cancer with bulky lymphadenopathy and a serum prostate-specific antigen of 295 μg/L. He received treatment with docetaxel chemotherapy plus prednisolone, but received just 3 cycles before treatment was stopped due to toxicity and lack of response (prostate-specific antigen was 276 μg/L 4 weeks after the last dose and there was a confirmed stable appearance on computed tomography scan). Unexpectedly, at follow-up 4 months later, the patient was clinically better; his prostate-specific antigen had dramatically improved to 4.1 μg/L and a re-staging computed tomography scan revealed complete resolution of his bulky lymphadenopathy. At the time, he was receiving a luteinising hormone-releasing hormone analogue but no other disease-modulating treatment. He remains well and asymptomatic, with his most recent serum prostate-specific antigen measuring 0.14 μg/L, 18 months after last receiving chemotherapy.. We report a case of complete and durable regression of metastatic castrate-resistant prostate cancer following palliative chemotherapy which, to the best of our knowledge, has not previously been reported in the literature.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Docetaxel; Goserelin; Humans; Lymphatic Metastasis; Male; Nitriles; Prostate; Prostatic Neoplasms; Taxoids; Tosyl Compounds; Treatment Failure; Treatment Outcome

Topics: Androgen Antagonists; Anilides; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Nitriles; Prostatic Neoplasms; Quality of Life; Tosyl Compounds

Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence.. Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization.. A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events.. Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).

Topics: Androgen Antagonists; Anilides; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Nitriles; Prostatic Neoplasms; Quality of Life; Tosyl Compounds

A 87-year-old man was diagnosed with prostate cancer (cT2aN0M0 Gleason score 4＋4 with initial prostate specific antigen of 23.4 ng/ml). Prostate cancer was treated with combined androgen blockade (goserelin acetate plus flutamide). He was administered goserelin acetate depot injection without any complications as an outpatient. However, 5 hours after he left the hospital, he came back to the hospital, complaining of lower abdominal pain. Abdominal computed tomography revealed a giant subcutaneous hematoma in the lower abdomen. Hemoglobin was 6.9 g/dl and blood pressure was lower than 80 mmHg. He was admitted and given a blood transfusion. Because of pre-disseminated intravascular coagulation score 6, it was hard to antagonize warfarin by Vitamin K (he had taken warfarin because of atrial fibrillation). Arteriography was performed and injury to a branch of the lower epigastric artery was found. Transcatheter arterial embolization was performed at the same time. Injecting goserelin acetate may cause severe arterial injury.

Topics: Aged, 80 and over; Antineoplastic Agents, Hormonal; Goserelin; Hematoma; Humans; Magnetic Resonance Imaging; Male; Prostatic Neoplasms; Radiography; Shock, Hemorrhagic

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

To study, adverse effects, quality of life (QoL), fatigue, and mental distress when intensity-modulated radiotherapy combined with androgen deprivation was applied to the whole pelvis as management of men with locally advanced prostate cancer.. In this prospective follow-up study 91 patients were treated by modern pelvic intensity-modulated radiotherapy and followed for 12 months. The patients completed a questionnaire with well-established instruments for adverse effects on urinary, bowel, and sexual function and bother, QoL, fatigue, and mental distress before treatment, and at 3 and 12 months follow-up.. After pelvic intensity-modulated radiotherapy the mean levels of sexual urinary and bowel function and bother were significantly reduced from baseline. Only urinary bother improved from 3 to 12-month follow-up. The levels of fatigue and QoL increased significantly from baseline to 3-month. Mental distress, fatigue, and QoL were significantly associated with both urinary and bowel function and bother at most time points, while so was not observed for sexual bother and function.. Men treated with pelvic intensity-modulated radiotherapy and androgen deprivation have significant reductions of all types of function and bother at 3 months, with minimal improvement to 12 months except for urinary bother. Fatigue possibly due to pelvic intensity-modulated radiotherapy increased at follow-ups.

Topics: Aged; Antineoplastic Agents, Hormonal; Fatigue; Goserelin; Humans; Longitudinal Studies; Male; Middle Aged; Pelvis; Prostatic Neoplasms; Quality of Life; Radiotherapy Dosage; Radiotherapy, Intensity-Modulated; Stress, Psychological; Surveys and Questionnaires

Topics: Androgen Antagonists; Anilides; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Nitriles; Prostatic Neoplasms; Quality of Life; Tosyl Compounds

Topics: Androgen Antagonists; Anilides; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Nitriles; Prostatic Neoplasms; Quality of Life; Tosyl Compounds

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Estramustine; Goserelin; Humans; Male; Neoplasm Recurrence, Local; Nitriles; Prostatic Neoplasms; Taxoids; Tosyl Compounds

To investigate acceptability of and preferences for physical activity participation in men receiving androgen-deprivation therapy (ADT) for prostate cancer, to identify influencing clinical and demographic factors, and to determine the percentage meeting national exercise guidelines.. Cross-sectional, descriptive.. Ambulatory care clinic of a large medical center.. 135 men receiving ADT.. A structured interview with a systematic procedure was used to elicit preferences for physical activity.. Exercise preferences and acceptability; evidence-based exercise intervention.. Participants expressed high levels of acceptability of and willingness to participate in aerobic (64% and 79%) and muscle-strengthening (79% and 81%) programs. Preferences were expressed for muscle-strengthening activities performed at home, either alone or in the company of a family member. Flexible, spontaneous, and self-paced programs were preferred. Significant associations were identified for distance, age, obesity, duration of ADT, and meeting American College of Sports Medicine (ACSM) and American Heart Association (AHA) guidelines. Nineteen percent of the study population met the guidelines for weekly physical activity.. High levels of expressed acceptance of and willingness to participate in physical activity programs as well as the small number of participants meeting ACSM and AHA guidelines suggest feasibility of and support the need for the development of exercise programs in this population.. Incorporating patient preferences and evidence-based practice is integral to providing high-quality patient-centered care and is the foundation for appropriate intervention programs. Insight from this study will facilitate the design of programs that better reflect actual preferences of prostate cancer survivors.. ADT-induced changes in body composition are believed to contribute to a reduction in insulin sensitivity and dyslipidemia that contribute to increased cardiovascular risk profile. Exercise has the potential to mitigate the harmful effects of ADT.

Topics: Adenocarcinoma; Aged; Androgens; Antineoplastic Agents, Hormonal; Bone Density; Cross-Sectional Studies; Exercise; Feasibility Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin Resistance; Male; Middle Aged; Muscle Strength; Neoplasms, Hormone-Dependent; Patient Acceptance of Health Care; Patient Preference; Practice Guidelines as Topic; Prostatic Neoplasms; Resistance Training; Socioeconomic Factors

We explored changes in hypoxia-inducible factor 1 (HIF1) signaling during androgen deprivation therapy (ADT) of androgen-sensitive prostate cancer xenografts under conditions in which no significant change in immunostaining of the hypoxia marker pimonidazole had occurred.. Gene expression profiles of volume-matched androgen-exposed and androgen-deprived CWR22 xenografts, with similar pimonidazole-positive fractions, were compared. Direct targets of androgen receptor (AR) and HIF1 transcription factors were identified among the differentially expressed genes by using published lists. Biological processes affected by ADT were determined by gene ontology analysis. HIF1α protein expression in xenografts and biopsy samples from 35 patients receiving neoadjuvant ADT was assessed by immunohistochemistry.. A total of 1344 genes showed more than 2-fold change in expression by ADT, including 35 downregulated and 5 upregulated HIF1 targets. Six genes were shared HIF1 and AR targets, and their downregulation was confirmed with quantitative RT-PCR. Significant suppression of the biological processes proliferation, metabolism, and stress response in androgen-deprived xenografts was found, consistent with tumor regression. Nineteen downregulated HIF1 targets were involved in those significant biological processes, most of them in metabolism. Four of these were shared AR and HIF1 targets, including genes encoding the regulatory glycolytic proteins HK2, PFKFB3, and SLC2A1. Most of the downregulated HIF1 targets were induced by hypoxia in androgen-responsive prostate cancer cell lines, confirming their role as hypoxia-responsive HIF1 targets in prostate cancer. Downregulation of HIF1 targets was consistent with the absence of HIF1α protein in xenografts and downregulation in patients by ADT (P<.001).. AR repression by ADT may lead to downregulation of HIF1 signaling independently of hypoxic fraction, and this may contribute to tumor regression. HIF1α expression is probably not a useful hypoxia biomarker during ADT in prostate cancer.

Topics: Androgen Antagonists; Anilides; Animals; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Combined Modality Therapy; Down-Regulation; Gene Expression Profiling; Goserelin; Humans; Hypoxia-Inducible Factor 1; Induction Chemotherapy; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Random Allocation; Receptors, Androgen; Stress, Physiological; Tosyl Compounds; Transcription, Genetic; Up-Regulation

The aim of this study was to evaluate acute adverse events and efficacy of three-dimensional intensity- modulated radiotherapy (IMRT) combined with endocrine therapy for intermediate and advanced prostate cancer.. Sixty-seven patients were treated with three-dimensional IMRT combined with maximum androgen blockade. The correlation between radiation-induced rectal injury and clinical factors was further analyzed.. After treatment, 21 patients had complete remission (CR), 37 had partial remission (PR), and nine had stable disease (SD), with an overall response rate of 86.5%. The follow-up period ranged from 12.5 to 99.6 months. Thirty-nine patients had a follow-up time of ≥ five years. In this group, three-year and five-year overall survival rates were 89% and 89.5%, respectively; three-year and five-year progression-free survival rates were 72% and 63%. In univariate analyses, gross tumor volume was found to be prognostic for survival (χ2 = 5.70, P = 0.037). Rates of leucopenia and anemia were 91.1% and 89.5%, respectively. Two patients developed acute liver injury, and a majority of patients developed acute radiation proctitis and cystitis, mainly grade 1/2. Tumor volume before treatment was the only prognostic factor influencing the severity of acute radiation proctitis (P < 0.05).. IMRT combined with endocrine therapy demonstrated promising efficacy and was well tolerated in patients with intermediate and advanced prostate cancer.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cystitis; Follow-Up Studies; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Nitriles; Proctitis; Prognosis; Prostatic Neoplasms; Radiation Injuries; Radiotherapy, Image-Guided; Radiotherapy, Intensity-Modulated; Survival Rate; Tosyl Compounds

Topics: Androgen Antagonists; Anilides; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Nitriles; Prostatic Neoplasms; Quality of Life; Tosyl Compounds

Topics: Androgen Antagonists; Anilides; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Nitriles; Prostatic Neoplasms; Quality of Life; Tosyl Compounds

Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence.. Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization.. A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P = 0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events.. Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life.

Topics: Androgen Antagonists; Anilides; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Nitriles; Prostatic Neoplasms; Quality of Life; Tosyl Compounds

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Testosterone

Luteinizing hormone (LH) during androgen-deprivation therapy (ADT) with gonadotropin-releasing hormone analogues (GnRHa) has been thought to be biologically inactive, and the regulation of LH during ADT with GnRHa is thus unknown. Insulin-like growth factor-1 (IGF-1) is involved in the regulation of cell proliferation and differentiation, and IGF-1 production in the liver is dependent on growth hormone (GH) secretion from the anterior pituitary. Despite the presence of IGF-1 receptors in the gonadotroph, associations between the GH/IGF-1 and pituitary-gonadal axes, e.g., whether IGF-1 elicits the LH secretion, remain unclear.. Seventy-one patients with localized prostate cancer, who received ADT with GnRHa, were prospectively studied based on their blood samples before treatment and after ADT for 6 months. We employed highly sensitive assays for measurement of serum testosterone (electrochemiluminescence immunoassay), GH/IGF-1 (radioimmunoassay), adrenocorticotropic hormone (ACTH: immunoradiometric assay), LH (chemiluminescent immunoassay), and dehydroepiandrosterone sulfate (DHEA-S: chemiluminescent enzyme immunoassay).. No correlation was noted between the pretreatment LH and IGF-1 levels; after ADT, the serum LH level was closely correlated with the IGF-1 concentration [Spearman's correlation coefficient (rs) = 0.370, P = 0.001]. The serum levels of androgens and gonadotropins reduced following ADT (P < 0.001 in all). The serum IGF-1 level increased (22 ± 6 nmol/L) compared with that at the baseline (19 ± 5 nmol/L) (P < 0.001), but no change was observed in the serum GH concentration between before and after ADT (1.4 ± 2.3 vs. 0.9 ± 0.9 μg/L, respectively, P = 0.691). The serum testosterone level was not correlated with the LH level either before or after ADT. The testosterone and DHEA-S levels after ADT were correlated with ACTH concentration (rs = 0.367, P = 0.002 and rs = 0.354, P = 0.002, respectively). We did not identify any correlations between the serum IGF-1 concentration and Gleason score, PSA value, or androgen levels.. During ADT with GnRHa, IGF-1 possibly promotes LH production, although its role is unclear. Associations among pituitary-gonadal, pituitary-adrenal, and GH/IGF-1 axes represented by IGF-1-mediated LH secretion and ACTH-mediated androgen synthesis are of interest, since both prostate epithelium proliferation and male anabolic activity are involved in these 3 axes. Assessment of oncologic outcomes is warranted for their significance in patients with prostate cancer.

Topics: Adrenocorticotropic Hormone; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Dehydroepiandrosterone Sulfate; Flutamide; Goserelin; Human Growth Hormone; Humans; Immunoassay; Insulin-Like Growth Factor I; Logistic Models; Luteinizing Hormone; Male; Middle Aged; Multivariate Analysis; Outcome Assessment, Health Care; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Androgen deprivation therapy (ADT) is a key primary treatment for advanced and metastatic prostate cancer and is an important neoadjuvant before radiotherapy. We evaluated 3.0 T dynamic contrast-enhanced MRI and diffusion-weighted (DW) MRI in monitoring ADT response. Twenty-three consecutive patients with prostate cancer treated by primary ADT were included. Imaging was performed at baseline and 3 months posttreatment with ADT. After 3 months therapy there was a significant reduction in all dynamic contrast-enhanced MRI parameters measured in tumor regions of interest (K(trans), k(ep), v(p), IAUGC-90); P < 0.001. Areas of normal-appearing peripheral zone showed no significant change; P = 0.285-0.879. Post-ADT, there was no significant change in apparent diffusion coefficient values in tumors, whilst apparent diffusion coefficient values significantly decreased in areas of normal-appearing peripheral zone, from 1.786 × 10(-3) mm(2) /s to 1.561 × 10(-3) mm(2) /s; P = 0.007. As expected the median Prostate-Specific Antigen (PSA) significantly reduced from 30 ng/mL to 1.5 ng/mL posttreatment, and median prostate volume dropped from 47.6 cm(3) to 24.9 cm(3) ; P < 0.001. These results suggest that dynamic contrast-enhanced MRI and diffusion-weighted MRI offer different information but that both could prove useful adjuncts to the anatomical information provided by T2-weighted imaging. dynamic contrast-enhanced as a marker of angiogenesis may help demonstrate ADT resistance and diffusion-weighted imaging may be more accurate in determining presence of tumor cell death versus residual tumor.

Topics: Aged; Aged, 80 and over; Androgen Receptor Antagonists; Anilides; Antineoplastic Agents, Hormonal; Contrast Media; Diffusion Magnetic Resonance Imaging; Feasibility Studies; Goserelin; Humans; Imaging, Three-Dimensional; Male; Middle Aged; Nitriles; Organometallic Compounds; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

The addition of androgen deprivation therapy (ADT) to definitive external beam radiation therapy (RT) improves outcomes in higher-risk prostate cancer patients. However, the benefit of ADT with salvage RT in post-prostatectomy patients is not clearly established. Our study compares biochemical outcomes in post-prostatectomy patients who received salvage RT with or without concurrent ADT.. Of nearly 2,000 post-prostatectomy patients, we reviewed the medical records of 191 patients who received salvage RT at the University of Pennsylvania between 1987 and 2007. Follow-up data were obtained by chart review and electronic polling of the institutional laboratory database and Social Security Death Index. Biochemical failure after salvage RT was defined as a prostate-specific antigen of 2.0 ng/mL above the post-RT nadir or the initiation of ADT after completion of salvage RT.. One hundred twenty-nine patients received salvage RT alone, and 62 patients received combined ADT and salvage RT. Median follow-up was 5.4 years. Patients who received combined ADT and salvage RT were younger, had higher pathologic Gleason scores, and higher rates of seminal vesicle invasion, lymph node involvement, and pelvic nodal irradiation compared with patients who received salvage RT alone. Patients who received combined therapy had improved biochemical progression-free survival (bPFS) compared with patients who received RT alone (p = 0.048). For patients with pathologic Gleason scores ≤7, combined RT and ADT resulted in significantly improved bPFS compared to RT alone (p = 0.013).. These results suggest that initiating ADT during salvage RT in the post-prostatectomy setting may improve bPFS compared with salvage RT alone. However, prospective randomized data are necessary to definitively determine whether hormonal manipulation should be used with salvage RT. Furthermore, the optimal nature and duration of ADT and the patient subgroups in which ADT could provide the most benefit remain open questions.

Topics: Analysis of Variance; Androgen Antagonists; Anilides; Combined Modality Therapy; Disease-Free Survival; Flutamide; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Nitriles; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy Dosage; Retrospective Studies; Salvage Therapy; Seminal Vesicles; Tosyl Compounds

To evaluate long-term clinical outcomes in cT1c-T3a prostate cancer patients following delayed-combined androgen blockade therapy.. From January 2001 to December 2004, 92 cT1c-T3a prostate cancer cases were enrolled. Medical castration and anti-androgen treatment were used sequentially as delayed-combined androgen blockade therapy. Time to prostate-specific antigen biochemical failure was estimated, and risk factors for prostate-specific antigen biochemical failure were evaluated.. The average patient age was 76.4 years (range, 59-91 years), the median observation period was 52.8 months (range, 26-106.6 months) and the median pre-treatment prostate-specific antigen level was 14 ng/ml (range, 3.68-492 ng/ml). The TNM classification distribution was as follows: T1c, n= 27; T2a, n = 39; T2b, n = 20; and T3a, n = 6. In the multivariate analysis, Gleason's score ≥8 (P < 0.05; hazard ratio, 3.02), prostate-specific antigen nadir >1.4 ng/ml (P = 0.001; hazard ratio, 8.76) and a half-life of the prostate-specific antigen level >1.2 months (P < 0.005; hazard ratio, 6.3) during the initial 6 months of luteinizing hormone-releasing hormone agonist monotherapy were significant independent risk factors for prostate-specific antigen biochemical failure with luteinizing hormone-releasing hormone agonist monotherapy. The high-risk group, which had at least one of these three risk factors, had a shorter time to prostate-specific antigen biochemical failure than the low-risk group, during luteinizing hormone-releasing hormone agonist monotherapy (P < 0.0001). For the total delayed-combined androgen blockade therapy observation period, the free-prostate-specific antigen biochemical failure rate was 88.3% at 5 years. Only a maintenance period following luteinizing hormone-releasing hormone agonist monotherapy (P < 0.005; hazard ratio, 16.8) was revealed to be a significant independent risk factor for prostate-specific antigen biochemical failure with total delayed-combined androgen blockade.. The free-prostate-specific antigen biochemical failure rate of delayed-combined androgen blockade therapy in our study was as valuable as those in other androgen deprivation therapy of previous reports.

Topics: Aged; Aged, 80 and over; Algorithms; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Drug Administration Schedule; Goserelin; Humans; Kaplan-Meier Estimate; Leuprolide; Male; Middle Aged; Multivariate Analysis; Neoplasm Grading; Neoplasm Staging; Nitriles; Odds Ratio; Predictive Value of Tests; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Assessment; Risk Factors; Time Factors; Tosyl Compounds; Treatment Failure; Treatment Outcome

to evaluate the effectiveness of primary hormonal treatment on localized and locally advanced prostate cancer, including the analysis on the survival predictive factors.. patients with localized (T1,T2N0M0) and locally advanced (T3, T4N0M0) prostate cancer who had received primary hormonal treatment between January 1995 and December 2009 were evaluated retrospectively based on their specific medical records at Department of Urology in Cipto Mangunkusumo Hospital (RSCM) and Dharmais Cancer Hospital (RSKD).. about 79 (29.9%) of 264 patients with localized and advanced local prostate cancer received primary hormonal treatment. In the localized prostate cancer group, mean survival was 58.3 months (range: 1.87-170.78) and 5-year survival was 77.3%; while in locally advanced prostate cancer patients, mean survival was 40.87 months (range 7.29-115.29) and 5-year survival was only 22.7%. Hemoglobin level was a significant clinical parameter of survival predictive factors for both localized and locally advanced prostate cancer groups. The lower the hemoglobin level, the survival will be shorter.. there were no significant differences between mean survival and 5-year survival rate, between localized and locally advanced prostate cancer patients who had received primary hormonal treatment. Hemoglobin level is survival predictive factors for localized and locally advanced prostate cancer patients.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Biomarkers; Combined Modality Therapy; Follow-Up Studies; Goserelin; Hemoglobins; Humans; Leuprolide; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Prostatic Neoplasms; Retrospective Studies; Survival Analysis; Treatment Outcome

What's known on the subject? and What does the study add? Previous reports, with small numbers of patients, have described the problem of incomplete testosterone suppression (>1.1 or 1.7 nmol/L) with LHRH agonists. Various predisposing factors have been suggested: different drug agents and patient factors such as age, pretreatment testosterone levels and weight. Such incomplete testosterone suppression has been shown in one small report to be associated with increased PSA failure rates and in another report in those with metastases, with worse survival. This study used testosterone assays that are more accurate at low levels than those used in most previous reports in a large dataset of 2196 men, and confirmed incomplete testosterone suppression (breakthrough) rates >1.7 nmol/L of 3.4% and >1.1 nmol/L of 6.6%. We showed that younger age was strongly associated with the risk of breakthrough, with a minor effect of increasing body mass index. Repeated breakthroughs were more common (16%) in those who had already had one breakthrough. Interim measures of cancer control (PSA kinetics during LHRH therapy) were inferior in those with a breakthrough, and those with breakthroughs between 1.1 and 1.7 nmol/L had worse long-term biochemical control rates.. • To describe breakthrough rates above castrate levels of testosterone, in a population-based series of men undergoing adjuvant luteinizing hormone-releasing hormone (LHRH) agonist therapy with curative radiation therapy. • To explore the predisposing factors for such breakthroughs and their impact on subsequent outcomes.. • All men treated for prostate cancer between 1998 and 2007 with curative radiation in the province of British Columbia, Canada were potentially eligible (n= 11752). Of these, 2196 fulfilled the eligibility criteria. • Serial testosterone measurements were obtained during continuous LHRH therapy. • Breakthrough rates >1.1 nmol/L and >1.7 nmol/L were calculated for each LHRH injection and for each patient course. • Predisposing factors were identified, and early surrogates of oncological outcome (neoadjuvant nadir and post-treatment nadir) were determined.. • The risk of a breakthrough >1.1 nmol/L was 6.6%, and >1.7 nmol/L was 3.4% per patient course and 5.4% and 2.2% per LHRH injection (inclusive ranges). • Repeated breakthroughs occurred in 16% of patients. • Younger men were more liable to breakthroughs (P < 0.001). • Early PSA kinetic surrogates of cancer control were inferior in those with breakthroughs. • Neither overall biochemical non-evidence of disease (bNED) nor survival were compromised, although subgroup analysis showed inferior 5-year bNED in those with breakthroughs of 1.1-1.7 nmol/L vs those without (58% vs 73%, respectively; P= 0.048).. • Breakthroughs with LHRH agonists occur occasionally per injection, but occur commonly per patient course of treatment, and adversely affect early surrogate measures of outcome. • The monitoring of testosterone levels during therapy is therefore advised.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Body Mass Index; Buserelin; Drug Therapy, Combination; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Retrospective Studies; Testosterone; Treatment Outcome

Despite a lack of consensus regarding effectiveness, androgen deprivation therapy (ADT) is a common treatment for non-metastatic, low-risk prostate cancer. To examine a particular clinical concern regarding the possible impact of ADT on cognition, the current study combined neuropsychological testing with functional magnetic resonance imaging (fMRI) to assess both brain activation during cognitive performance as well as the integrity of brain connectivity.. In a prospective observational cohort analysis of men with non-metastatic prostate cancer at a Veterans Affairs medical center, patients receiving ADT were compared with patients not receiving ADT at baseline and at 6 months. Assessments included fMRI, the N-back task (for working memory), the stop-signal task (for cognitive control), and a quality of life questionnaire.. Among 36 patients enrolled (18 in each group), 30 completed study evaluations (15 in each group); 5 withdrew participation and 1 died. Results for the N-back task, stop-signal task, and quality of life were similar at 6 months vs. baseline in each group. In contrast, statistically significant associations were found between ADT use (vs. non use) and decreased medial prefrontal cortical activation during cognitive control, as well as decreased connectivity between the medial prefrontal cortex and other regions involved with cognitive control.. Although ADT for 6 months did not affect selected tests of cognitive function, brain activations during cognitive control and functional brain connectivity were impaired on fMRI. The long-term clinical implications of these changes are not known and warrant future study.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Brain; Cognition; Cohort Studies; Goserelin; Humans; Magnetic Resonance Imaging; Male; Memory; Middle Aged; Neuropsychological Tests; Nitriles; Prospective Studies; Prostatic Neoplasms; Psychomotor Performance; Quality of Life; Surveys and Questionnaires; Tosyl Compounds; Treatment Outcome

We report a case of squamous differentiated prostate carcinoma that developed after combination endocrine therapy for adenocarcinoma of the prostate. The patient was a 68-year-old man who visited our hospital with microscopic hematuria. His serum prostate-specific antigen (PSA) level was 7. 06 ng/ml. Transperineal needle biopsy was performed and histological examinations indicated moderately differentiated adenocarcinoma with a Gleason score of 4 + 4 = 8. Computed tomography showed swelling of left external iliac lymph node. The clinical stage was T3aN1M0. Six weeks after combination endocrine therapy using goserelin acetate and bicalutamide, the patient underwent radical prostatectomy and bilateral pelvic lymphadenectomy. Histopathological examination of the surgical specimen demonstrated squamous cell carcinoma of the prostate with very small areas of adenocarcinoma. The treatment measure was changed from endocrine therapy to combination chemotherapy consisting of docetaxel, cisplatin, and 5- FU. Eighteen month has passed after the surgery without any evidence of distant metastasis.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Docetaxel; Fluorouracil; Goserelin; Humans; Lymph Node Excision; Male; Nitriles; Prostatectomy; Prostatic Neoplasms; Taxoids; Tosyl Compounds

E26 transformation-specific-1 (ETS-1), an ETS family transcription factor, has been reported to play an important role in a variety of physiological and pathological processes, but clinical implications of ETS-1 expression in prostate cancer (PCa), particularly high-risk cases, including response to androgen-deprivation therapy (ADT) have yet to be elucidated. We examined the expression of ETS-1 using immunohistochemical staining of paraffin-embedded prostate carcinoma tissue obtained by needle biopsy from 69 mostly advanced PCa patients. ETS-1 expression was compared with the clinicopathological characteristics of the 69 patients, including 25 who underwent ADT as a primary treatment. As a result, PCa patients with higher expression of ETS-1 were significantly more likely to be of high stage and high Gleason score (P<0.05). There was no significant association between ETS-1 expression and the initial prostate-specific antigen (PSA) level. In the 25 patients treated by ADT, the staining score for ETS-1 was significantly associated with rapid development of castration-resistant disease within 24 months (P<0.05), whereas the Gleason score and PSA level were not. In conclusion, increased ETS-1 expression was associated with a higher stage, higher Gleason score and shorter time to castration-resistant progression. These data suggest that immunostaining for ETS-1 could be a molecular marker for predicting a poor clinical outcome for PCa patients, particularly those with high-risk disease.

Topics: Aged; Disease Progression; Goserelin; Humans; Immunohistochemistry; Leuprolide; Male; Neoplasm Grading; Orchiectomy; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Proto-Oncogene Protein c-ets-1

Osteosarcoma of the prostate is a rare finding. These tumours usually occur years after radiotherapy for prostate cancer. We report the case of a 74-year-old man with prostate cancer who had been treated with radiotherapy and androgen deprivation therapy. The man presented with urinary retention and his prostate was transurethrally resected. The histopathological investigation showed formations of a poorly differentiated osteosarcoma in the prostate. Because of serious comorbidities we decided to withhold chemotherapy considering its potential side effects. The man died a few months after the diagnosis of osteosarcoma in the prostate with the disease in a metastatic stage. In conclusion, osteosarcoma of the prostate is a rarely reported consequence of radiotherapy in patients with prostate cancer and is characterised by poor life expectancy.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Combined Modality Therapy; Disease Progression; Fatal Outcome; Goserelin; Humans; Male; Neoadjuvant Therapy; Neoplasm Staging; Neoplasms, Radiation-Induced; Neoplasms, Second Primary; Nitriles; Prostatic Neoplasms; Tosyl Compounds; Transurethral Resection of Prostate

The antivascular effects of androgen deprivation have been investigated in animal models; however, there has been minimal investigation in human prostate cancer. This study tested the hypothesis that androgen deprivation causes significant reductions in human prostate tumor blood flow and the induction of hypoxia at a magnitude and in a time scale relevant to the neoadjuvant setting before radiotherapy.. Twenty patients were examined, each with five multi-parameter magnetic resonance imaging scans: two scans before the commencement of androgen suppression, one scan after 1 month of hormone treatment, and two further scans after 3 months of therapy. Quantitative parametric maps of the prostate informing on relative blood flow (rBF), relative blood volume (rBV), vascular permeability (transfer constant [K(trans)]), leakage space (v(e)) and blood oxygenation (intrinsic relaxivity [R(2)∗]) were calculated.. Tumor blood volume and blood flow decreased by 83% and 79%, respectively, in the first month (p < 0.0001), with 74% of patients showing significant changes. The proportion of individual patients who achieved significant changes in T1 kinetic parameter values after 3 months of androgen deprivation for tumor measurements was 68% for K(trans) and 53% for v(e) By 3 months, significant increases in R(2)∗ had occurred in prostate tumor, with a rise of 41.1% (p < 0.0001).. Androgen deprivation induces profound vascular collapse within 1 month of starting treatment. Increased R(2)∗ in regions of prostate cancer and a decrease in blood volume suggest a reduction in tumor oxygenation.

Topics: Aged; Androgen Antagonists; Anilides; Blood Volume; Capillary Permeability; Cell Hypoxia; Goserelin; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoadjuvant Therapy; Nitriles; Oxygen; Prospective Studies; Prostatic Neoplasms; Regional Blood Flow; Reproducibility of Results; Time Factors; Tosyl Compounds

Topics: Adenocarcinoma; Adenoma; Aged; Antineoplastic Agents, Hormonal; Gonadotrophs; Goserelin; Humans; Male; Pituitary Neoplasms; Prostatic Neoplasms

To identify whether veterans receiving androgen-deprivation therapy (ADT) are screened at any time by bone mass measurement.. Cross-sectional study.. Veterans Administration Tennessee Valley Healthcare System (VA-TVHS).. All male veterans who received at least one dose of goserelin or leuprolide within the fiscal years October 1, 2005, through September 30, 2009.. Data from patients' charts were extracted for demographic information (race, age, and weight prior to the initial injection); date of initiation of therapy; the use of calcium, vitamin D, bisphosphonate, or calcitonin therapy; and documented bone-mineral density testing.. To determine whether veterans receiving ADT with goserelin or leuprolide for prostate cancer were screened at any time for BMD more or less than rates as documented in previous literature.. 22.8% of veterans were screened for BMD, which was statistically significant when compared with results found in previous literature.. Although rates of BMD testing were higher at VA-TVHS compared with previous literature, this rate is still low given the well-known risk of accelerated osteoporosis associated with ADT.

Topics: Aged; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Bone Density; Cross-Sectional Studies; Goserelin; Humans; Leuprolide; Male; Osteoporosis; Prostatic Neoplasms; Risk Assessment; Veterans

Topics: Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms

Men with castrate resistant prostate cancer have limited treatment options. Although luteinizing hormone-releasing hormone agonists are in the same class, they are slightly different in their pharmacology. We determined whether rechallenging patients with prostate cancer, who were receiving a luteinizing hormone-releasing hormone analogue but had progression, with a different luteinizing hormone-releasing hormone analogue (goserelin or leuprolide acetate) would result in a prostate specific antigen response. Secondary objectives were to calculate the PSA response and determine whether sequence order impacted the response.. We performed a retrospective, ethics approved review of the records of patients with prostate cancer at multiple institutions who received a luteinizing hormone-releasing hormone analogue (goserelin or leuprolide acetate), experienced progression, as measured by 2 consecutive prostate specific antigen increases, and were rechallenged with the other analogue (goserelin or leuprolide acetate). Prostate specific antigen and relevant clinical data were obtained and statistical analysis was done.. Of 39 available men 27 (69%) had decreased prostate specific antigen after 3 months of switching regimens. The median change in prostate specific antigen was -1.5 (IQR -10.0, 0.8), indicating a statistically significant decrease (p=0.01). The median percent prostate specific antigen change for leuprolide acetate to goserelin was -69.3% (IQR -81.5, 26.2) and for goserelin to leuprolide acetate it was -6.4% (IQR -61.7, 21.8, p=0.05). Median time to a subsequent prostate specific antigen increase was 5.2 months (95% CI 3.5-17.4).. Prostate specific antigen decreased after switching luteinizing hormone-releasing hormone therapies. This decrease appeared most significant in the group that switched from leuprolide acetate to goserelin. The duration of response after switching was approximately 5 months. The study is limited by its retrospective nature but should encourage prospective evaluation of this observation.

Topics: Aged; Aged, 80 and over; Disease Progression; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies

We studied whether hormonal therapy, (neo)adjuvant to radiotherapy for localized prostate cancer, is related to an increase in depression and whether this is caused by the hormonal therapy itself or by the relatively poor prognosis of patients who get (neo)adjuvant hormonal therapy.. Between 2002 and 2005, 288 patients, irradiated for prostate cancer (T1-3N0M0), were studied prospectively in two clinics. In one clinic almost all patients received (neo)adjuvant androgen deprivation (Bicalutamide+Gosereline). In a second clinic hormonal therapy was prescribed mainly for high risk patients. This allowed us to separate the effects of hormonal therapy and the patient's prognosis.. During the course of hormonal therapy, depression was significantly heightened by both hormone use (p<0.001) and poor prognosis (p<0.01). After completion of hormonal therapy, poor prognosis continued to affect the depression score (p<0.01). The increase was, however, small.. Depression was mildly increased in patients receiving hormonal therapy. The increase appeared to be related to both the hormone therapy itself and the high risk status of patients. High risk status, with the associated poor prognosis, had a more sustained effect on depression. The rise was statistically significant, but was too small, however, to bear clinical significance.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Depression; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Nitriles; Prognosis; Prospective Studies; Prostatic Neoplasms; Tosyl Compounds

In Japan, androgen deprivation therapy is employed as the primary therapy for prostate cancer in more than 50% of patients, which is a percentage larger than that in the USA. The adverse effects of androgen deprivation therapy on body composition and lipid profile associated with metabolic syndrome have been reported mainly in Caucasian populations, and few studies have been performed in East Asian populations, including Japanese.. This study enrolled 39 Japanese patients who were starting to receive androgen deprivation therapy for prostate cancer. Subjects were evaluated at baseline and at 3, 6, 9 and 12 months. Body composition and lipid profiles were measured by bioelectrical impedance analysis and using blood samples, respectively.. The volume of fat and visceral fat was significantly increased 6 months after the treatment and continued to increase until 12 months. On the other hand, skeletal muscle was significantly decreased during the same period. The serum concentration of total cholesterol and low-density lipoprotein cholesterol increased significantly over the same period.. Androgen deprivation therapy changed the body composition and lipid profile of men with prostate cancer. It was demonstrated that even Japanese patients with prostate cancer who are treated with androgen deprivation therapy have the risk of developing metabolic syndrome.

Topics: Adipose Tissue; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Asian People; Biomarkers, Tumor; Body Composition; Electric Impedance; Gonadotropin-Releasing Hormone; Goserelin; Humans; Intra-Abdominal Fat; Japan; Lipid Metabolism; Male; Metabolic Syndrome; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Primary hormonal therapy has been mostly used for patients with advanced prostate cancer, as international guidelines do not recommend its use for patients at earlier disease stages. However, there seems to be a discrepancy between the guideline recommendations and clinical practice on the use of primary androgen deprivation therapy for localized prostate cancer in Japan. Therefore, we retrospectively analyzed a single-institution experience in primary combined androgen blockade (CAB) for localized prostate cancer.. The study included 187 patients with T1c-T3a prostate cancer unsuitable for local definitive treatment and treated with primary CAB. Clinical outcomes, predictive factors of PSA relapse and adverse events were investigated.. The progression-free, disease-specific, and overall survival rates of all patients at 5 years were 63.0, 99.4 and 95.9%, respectively. Of the several parameters isolated as predictors of prostate-specific antigen (PSA) progression, nadir PSA level and the percentage of positive biopsy cores (%PBC) remained as independent prognostic factors on multivariate analysis. Toxicities were mild to moderate and well tolerated.. Primary CAB treatment brought initial disease control without relapse in the majority of our selected cases. The %PBC may help predict time to relapse in the pretreatment setting. The results implicate that CAB can be an option as a primary treatment for clinically localized prostate cancer unsuitable for local definitive treatment. To confirm the exact efficacy of primary CAB, these findings should be reviewed in a large cohort of patients with long-term follow-up from various viewpoints, including disease control, toxicities, quality-of-life and medical cost.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Androgens; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chlormadinone Acetate; Disease-Free Survival; Flutamide; Follow-Up Studies; Goserelin; Humans; Japan; Kaplan-Meier Estimate; Leuprolide; Male; Middle Aged; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Tosyl Compounds; Treatment Outcome

The first case was in a 73-year-old man with macrohematuria. The second case was in a 59-year-old man with pollakiuria. Their serum prostate specific antigen levels were slightly elevated and urinary cytology was negative. Histological examination by prostatic needle biopsy and biopsy from bladder neck showed prostatic ductal adenocarcinoma. Clinical stage on computed tomography and magnetic resonance imaging was T4N0M0 in both cases. After 10-month maximal androgen blockade(MAB) and arterial chemotherapy using reservoir system, radiation therapy was performed. After that, low dose FP-chemotherapy(5-fluorouracil 600 mg/day, cisplatinum 10 mg/day) was performed for 28 days in the first case. At present, there are no signs of recurrence or metastasis in either case.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Fluorouracil; Goserelin; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Prostatic Neoplasms; Treatment Outcome

The objective of this study was to assess the usefulness of ice cubes and vapocoolant spray for relieving pain induced by goserelin acetate injections.. Fourty-seven patients with prostate cancer receiving hormonal manipulation by goserelin acetate were enrolled in this study. They received goserelin acetate injections after analgesic pretreatments with ice cubes until March 2009, and with vapocoolant spray and ethyl chroride after April 2009. We had them fill out a questionnaire asking whether they preferred to continue cooling pretreatments. We assessed the pricking pain using the face scale(FS)and the numerical rating scale(NRS).. The median FS and NRS scores at the first pretreatment(ice cube or vapocoolant spray)were lower than those at no pretreatment(p<0. 01 in both scores). Thirty-nine patients(83. 0%)preferred cooling pretreatment. Only 5 patients preferred no pretreatment. The differences in the median FS score and NRS score between ice cubes and vapocoolant spray were not significant(p=0. 353 in FS, p=0. 120 in NRS). No adverse events associated with the cooling pretreatment occurred except for late-onset subcutaneous hemorrhages in 2 cases.. The local cooling at the injection site of goserelin acetate was effective irrespective of the method(ice cube or vapocoolant spray)for the relief of pricking pain without causing serious complications.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cold Temperature; Goserelin; Humans; Ice; Infusions, Intravenous; Male; Middle Aged; Pain; Prostatic Neoplasms; Surveys and Questionnaires; Treatment Outcome

Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. In the present study, we evaluated the oxidative status and antioxidant defense in patients with prostate cancer (PCa) taking into consideration: treatment, Gleason score and bone metastasis. For this, we measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasma and erythrocyte thiol levels and serum vitamin C and E concentration. This study was performed on 55 patients with PCa and 55 healthy men. TBARS levels and serum protein carbonylation were higher in PCa patients than in controls and altered levels of antioxidants were found in these patients. CAT activity was decreased and SOD activity was higher in PCa patients when compared with controls. Non-protein thiol levels were increased, however, serum vitamin C and vitamin E content were reduced in PCa patients when compared with controls. In addition, different parameters analyzed in PCa patients based on metastasis, treatment and Gleason score showed changes in oxidative stress biomarkers and antioxidant defenses. These findings may indicate an imbalance in the oxidant/antioxidant status, supporting the idea that oxidative stress plays a role in PCa, moreover, the oxidative profile appear to be modified by bone metastasis, treatment and Gleason score.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Ascorbic Acid; Bone Neoplasms; Catalase; Cyproterone Acetate; Erythrocytes; Goserelin; Humans; Lipid Peroxidation; Male; Middle Aged; Neoplasm Grading; Oxidative Stress; Prostatic Neoplasms; Protein Carbonylation; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

Prostate cancer progression depends in part on the complex interactions between testosterone, its active metabolite DHT, and androgen receptors. In a metastatic setting, the first line of treatment is the elimination of testosterone. However, such interventions are not curative because cancer cells evolve via multiple mechanisms to a castrate-resistant state, allowing progression to a lethal outcome. It is hypothesized that administration of antiandrogen therapy in an intermittent, as opposed to continuous, manner may bestow improved disease control with fewer treatment-related toxicities. The present study develops a biochemically motivated mathematical model of antiandrogen therapy that can be tested prospectively as a predictive tool. The model includes "personalized" parameters, which address the heterogeneity in the predicted course of the disease under various androgen-deprivation schedules. Model simulations are able to capture a variety of clinically observed outcomes for "average" patient data under different intermittent schedules. The model predicts that in the absence of a competitive advantage of androgen-dependent cancer cells over castration-resistant cancer cells, intermittent scheduling can lead to more rapid treatment failure as compared to continuous treatment. However, increasing a competitive advantage for hormone-sensitive cells swings the balance in favor of intermittent scheduling, delaying the acquisition of genetic or epigenetic alterations empowering androgen resistance. Given the near universal prevalence of antiandrogen treatment failure in the absence of competing mortality, such modeling has the potential of developing into a useful tool for incorporation into clinical research trials and ultimately as a prognostic tool for individual patients.

Topics: Algorithms; Androgen Antagonists; Animals; Antineoplastic Agents, Hormonal; Cells, Cultured; Disease Progression; Drug Administration Schedule; Flutamide; Goserelin; Humans; Male; Models, Biological; Orchiectomy; Organ Size; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Rats; Rats, Sprague-Dawley; Receptors, Androgen; Testosterone; Treatment Outcome

To assess whether short-course total androgen blockade vs. a luteinizing hormone-releasing hormone (LHRH) agonist alone affects the risk of prostate cancer-specific mortality (PCSM) in men with localized but high-risk disease treated with radiotherapy.. The study cohort comprised 628 men with T1-T4, N0, M0 prostate cancer with high-risk disease (prostate-specific antigen level >20 ng/mL, Gleason score >or=8, or clinical category >or=T3) treated with 45 Gy of external beam radiotherapy followed by a brachytherapy boost in addition to receiving a median of 4.3 (interquartile range [IQR], 3.6-6.4) months of hormonal blockade with an LHRH agonist plus an antiandrogen or monotherapy with an LHRH agonist. Fine and Gray's multivariable regression analysis was used to determine whether combination androgen suppression therapy (AST) vs. monotherapy affected the risk of PCSM, adjusting for treatment year, duration of AST, age, and known prognostic factors.. After a median follow-up of 4.9 (IQR, 3.5-6.5) years, men receiving combination AST had a lower risk of PCSM than those treated with monotherapy (adjusted hazard ratio [AHR], 0.18; 95% confidence interval [CI], 0.04-0.90; p = 0.04). An increasing prostate-specific antigen level (AHR, 2.70; 95% CI, 1.64-4.45; p < 0.001) and clinical category T3/4 disease (AHR, 29.6; 95% CI, 2.88-303.5; p = 0.004) were also associated with an increased risk of PCSM.. In men with localized but high-risk prostate cancer treated with external beam radiotherapy and brachytherapy, short-course AST with an LHRH agonist plus an antiandrogen is associated with a decreased risk of PCSM when compared with monotherapy with an LHRH agonist.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Drug Therapy, Combination; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Multivariate Analysis; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Regression Analysis

To determine if the testosterone level achieved with androgen-deprivation therapy (ADT) is directly related to survival and risk of death in men with metastatic prostate cancer, as agonistic analogues of luteinizing hormone-releasing hormones (LHRH) are indicated for palliative treatment of these patients, but there is no consensus about the utility of serum testosterone measurements during the follow-up, and their possible prognostic value.. We retrospectively reviewed 129 consecutive patients with a histological diagnosis of metastatic bony-only prostate cancer and previously untreated with ADT. They were treated with 3 months of goserelin. Testosterone and prostate-specific antigen (PSA) levels were measured in all patients every 3 months for the duration of the follow-up. The following variables were recorded: age, stage, Gleason score, basal PSA level, basal testosterone level, PSA nadir, time to PSA nadir, testosterone after 6 months, testosterone nadir and time to testosterone nadir. Data were analysed using Cox's proportional hazards models, with the primary endpoint being cancer-specific survival.. The mean (SD) basal PSA level was 185.8 (344.1) ng/mL, and the mean nadir PSA level 2.7 (8.6) ng/mL. The mean testosterone levels at baseline, 6 months and the nadir were 440 (200), 40 (40) and 21 (15) ng/dL. With a mean follow-up of 47.5 (29.7) months, 71 patients were dead (55%) and 78 were alive (45%) at the time of analysis. Statistical analysis using Cox's model showed that in these patients the risk of death was directly correlated not only to Gleason score (P < 0.01) and to the 6-month PSA level (P < 0.01), but also to the 6-month serum testosterone level (hazard ratio 1.32, P < 0.05).. These results suggest a direct correlation between the risk of death and testosterone levels achieved during ADT. Based on the present results, lowering the testosterone level as much as possible should be the goal of ADT in patients with metastatic prostate cancer, as this might affect patient survival.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Epidemiologic Methods; Goserelin; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Testosterone; Treatment Outcome

Topics: Antineoplastic Agents, Hormonal; Drug Administration Schedule; Evidence-Based Medicine; Goserelin; Humans; Male; Prostatic Neoplasms; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Selection Bias; Treatment Outcome

In order to assess the efficacy and toxicity of oral estramustine phosphate (EMP) administration, low-dose EMP monotherapy (study 1) and very low-dose EMP therapy with luteinizing hormone-releasing hormone (LH-RH) agonist (study 2) were conducted in previously untreated prostate cancer and long-term outcomes were compared between the 2 study groups.. Studies 1 and 2 were independently performed beginning in June 1999 and November 2001, respectively. Study 1 was composed of 87 patients including 85 assessable patients. All 108 patients recruited for study 2 were assessable. Low-dose EMP monotherapy (2 capsules/day or 280 mg/day) was used in study 1 and very low-dose EMP (1 capsule/day or 140 mg/day) combined with LH-RH agonist was adopted in study 2.. Overall prostate specific antigen (PSA) -response rates in studies 1 and 2 were 92.3% and 94.2%, respectively, and overall toxicity rates were 54.1% and 38.9%, respectively. EMP discontinuation due to side effects was encountered more often in study 1 (45.9%) than in study 2 (27.8%). Among the adverse side effects gastrointestinal toxicity was most prevalent in both studies. One patient died of acute pulmonary embolism in study 1, but no one died in study 2. There were 6 cancer deaths in the gastrointestinal tract in study 1 but only 2 cancer deaths in study 2.. Our data indicate that the overall PSA response rate was comparable between both studies. However, rates in overall toxicity and drug discontinuation were higher in study 1 than in study 2. We consider that study 2 is more promising for the treatment of previously untreated advanced prostate cancer, although the rate of adverse side effects is still high as compared with other hormonal therapies. In order to overcome the high toxicity rate, especially the gastrointestinal toxicity, we recently elaborated a method employing tailor-made medicine using SNPs of 1A1 gene in cytochrome P-450 for decreasing the rate of gastrointestinal toxicity. Using this method of patient selection, study 3 has been successfully launched on September 2005 with high drug compliance. Better clinical results are being accumulated.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Biomarkers, Tumor; Cause of Death; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Estramustine; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Injections, Intravenous; Kaplan-Meier Estimate; Leuprolide; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Aged, 80 and over; Antineoplastic Agents, Hormonal; Goserelin; Hair Color; Herpes Zoster; Humans; Male; Melanocytes; Prostate-Specific Antigen; Prostatic Neoplasms; Severity of Illness Index

Goserelin acetate, which is injected through a 16-gauge needle, makes some patients feel substantial, although tolerable, pain. We tried to clarify whether injection pain was reduced by icing the skin at the injection site.. Pain associated with the injection of goserelin acetate was prospectively evaluated in 48 patients who had received an 10.8-mg goserelin injection at least once previously. In this study, the first injection was administered by usual methods, and 3 months later a second injection was administered after icing the skin at the injection site. Pain intensity was evaluated by visual analogue scale (VAS) pain score.. VAS pain scores for the usual injection method were 32.4 ± 21.7 mm [mean ± 2 standard deviation (SD)] and was significantly lower (16.4 ± 17.9) for the icing method (p = 0.001, paired t test). Thirty-three (68.8%), eight (16.7%), and seven (14.6%) of the 48 patients reported a decrease, no change, and increase, respectively, in VAS pain score by the icing method.. Icing at the injection site of goserelin acetate is a safe and effective method to reduce injection pain. This method can be easily performed in daily practice if a patient complains of pain at the injection site.

Topics: Aged; Aged, 80 and over; Analgesia; Antineoplastic Agents, Hormonal; Chi-Square Distribution; Cold Temperature; Goserelin; Humans; Injections, Subcutaneous; Japan; Male; Middle Aged; Pain; Pain Measurement; Prospective Studies; Prostatic Neoplasms; Skin Temperature

Gonadotrophin-releasing hormone agonists (GnRHAs) are used in many clinical conditions, particularly prostate cancer. There have been a few case reports of apoplexy from a previously undiagnosed pituitary tumour, occurring within hours to days of initiation of GnRHA therapy. We report a case of delayed onset pituitary apoplexy following GnRHA therapy. A 71-year-old man presented three weeks after onset of headache and vision loss. On examination, he was blind in the right eye with an intact nasal field of vision in the left eye. Two months before presentation, he had a subcutaneous GnRHA (Goserelin) implant for treatment of locally advanced prostate cancer (Gleeson 4+3). An MRI scan revealed a large sellar/suprasellar mass. His follicle stimulating hormone (FSH) and luteinizing hormone (LH) levels were grossly elevated. A trans-sphenoidal endoscopic decompression of the pituitary tumour was performed. His vision improved post-operatively and his FSH, LH, testosterone, prostate specific antigen (PSA) levels returned to normal levels. Histopathologic studies revealed a pituitary adenoma, which stained positive for FSH and LH. The prostate cancer management was changed to an anti-androgen agent and a GnRH antagonist. This case demonstrates that pituitary apoplexy can develop up to eight weeks after the initiation of treatment for prostate cancer with GnRHAs.

Topics: Aged; Drug Implants; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Pituitary Apoplexy; Prostatic Neoplasms; Time Factors

In 1941 Huggins and Hodges demonstrated that castration slowed progression of prostate cancer. Treatment with a luteinizing hormone releasing hormone (LHRH) agonist is a standard alternative to surgical castration for patients with prostate cancer and metastases. We evaluated patients with prostate cancer undergoing long-acting LH-RH agonist hormone therapy to determine the length of time that serum testosterone remains at castration level. Between June 2007 and October 2009, we studied 73 patients treated with LH-RH agonist. Castrate serum testosterone was defined at 50 ng/dl and less. The interval of administration of LH-RH agonist was extended to 5 months, and the testosterone level was measured. The testosterone level was 50 or less in almost all patients at 5 months after long-acting LH-RH therapy. The ratio of patients to whom dosing of LH-RH agonist was terminated who have a testosterone level of 50 ng/dl and lower was at 100% to month 7 and 7% to months 10 -19. We believe that therapy whereby long-acting LH-RH agonist is dosed may be extended to 5 to 7 months if male hormone values are monitored. Our data suggest that using serum testosterone to guide LH-RH hormone dosing is efficacious and cost-effective.

Topics: Aged; Autacoids; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Monitoring, Physiologic; Prostatic Neoplasms; Testosterone

We have investigated the effects of short-term neoadjuvant and long-term androgen deprivation therapies (ADTs) on β-microseminoprotein (MSMB) and cysteine-rich secretory protein-3 (CRISP3) expression in prostate cancer patients. We also studied if MSMB expression was related to genotype and epigenetic silencing. Using an Affymetrix cDNA microarray analysis, we investigated the expression of MSMB, CRISP3, androgen receptor (AR), KLK3 and Enhancer of Zeste Homologue-2 (EZH2) in tissue from prostate cancer patients receiving (n=17) or not receiving (n=23) ADT before radical prostatectomy. MSMB, CRISP3 and AR were studied in tissue from the same patients undergoing TURP before and during ADT (n=16). MSMB genotyping of these patients was performed by TaqMan PCR. MSMB and KLK3 expression levels decreased during ADT. Expression levels of AR and CRISP3 were not affected by short-term ADT but were high in castration-resistant prostate cancer (CRPC) and metastases. Levels of EZH2 were also high in metastases, where MSMB was low. Genotyping of the MSMB rs10993994 polymorphism showed that the TT genotype conveys poor MSMB expression. MSMB expression is influenced by androgens, but also by genotype and epigenetic silencing. AR and CRISP3 expression are not influenced by short-term ADT, and high levels were found in CRPC and metastases.

Topics: Aged; Androgen Antagonists; Biomarkers, Tumor; Carcinoma; Epigenesis, Genetic; Flutamide; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genotype; Goserelin; Humans; Male; Microarray Analysis; Middle Aged; Prostatic Neoplasms; Prostatic Secretory Proteins; Salivary Proteins and Peptides; Seminal Plasma Proteins

Although androgen deprivation therapy (ADT) has a marked impact on the androgen milieu in vivo and outcomes of prostate cancer (PCa), it remains unclear which parameters reflect the androgen milieu during ADT or whether the milieu is associated with PCa aggressiveness.. Seventy-two patients with localized PCa were prospectively studied based on their blood samples before and after ADT for 6 months. Serum androgens and related values were measured.. Before ADT, there was no correlation between the serum prostate-specific antigen (PSA) and androgen levels. After ADT, the serum PSA levels were correlated with each level of serum testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone-sulfate (DHEA-S), and 3alpha-diol G (P < 0.010 in all). Before ADT, patients with Gleason score of > or = 8 were likely to have lower serum testosterone levels than those with Gleason score of < or = 6 (P = 0.058). After ADT, conversely, the testosterone levels in patients with Gleason score of > or = 8 appeared to be higher than in those with Gleason score of < or = 6 (P = 0.060). The serum DHEA-S level was correlated with Gleason score before and after ADT (P = 0.050 and P = 0.040, respectively).. The serum PSA levels well reflect the androgen milieu in localized PCa patients receiving ADT, which can be explained by the Saturation Model and disease control. The androgen milieu in men with high Gleason score PCa is probably less affected by conventional ADT than that in men with low score cancer, which was suggested to be associated with adrenal androgen levels.

Topics: Aged; Androgens; Antineoplastic Agents, Hormonal; Chi-Square Distribution; Flutamide; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Bone Neoplasms; Goserelin; Humans; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Purpura, Thrombotic Thrombocytopenic; Tosyl Compounds

Primary androgen ablation leads to symptomatic improvement and a reduction in prostate-specific antigen (PSA) serum levels in patients with advanced prostate cancer, but all patients eventually become refractory to hormone therapy with progression of the disease and a life expectancy of about a year. We describe a patient who developed castration resistance, was treated with vinorelbine, and continues to be progression free on therapy with luteinizing hormone releasing hormone agonists alone, more than 2.5 years following cessation of treatment with vinorelbine.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Goserelin; Humans; Male; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome; Vinblastine; Vinorelbine

We elucidated the regulatory mechanism of adrenal androgen synthesis and examined the influence of pituitary-adrenal axis activity on prostate specific antigen during androgen deprivation therapy.. A total of 72 patients with localized prostate cancer were prospectively studied based on blood samples before and after androgen deprivation therapy for 6 months. Serum pituitary hormones, androgens and prostate specific antigen were measured using highly sensitive assays.. After androgen deprivation therapy serum levels of luteinizing hormone, follicle-stimulating hormone, testosterone, dehydroepiandrosterone sulfate, androstenedione and prostate specific antigen decreased compared with those at the baseline (all values p <0.001). No difference was noted between serum levels before and after androgen deprivation therapy in growth hormone (p = 0.098) and adrenocorticotropic hormone (p = 0.101). Each serum level of luteinizing hormone, follicle-stimulating hormone and growth hormone after androgen deprivation therapy was not correlated with the serum levels of androgens or prostate specific antigen. The serum adrenocorticotropic hormone level after androgen deprivation therapy was correlated with the serum levels of testosterone (p = 0.002), dehydroepiandrosterone sulfate (p = 0.002), androstenedione (p = 0.006) and prostate specific antigen (p <0.001). Serum dehydroepiandrosterone sulfate and androstenedione levels were also correlated with serum prostate specific antigen (p <0.001 and p = 0.002, respectively).. In patients treated with androgen deprivation therapy the pituitary-adrenal axis mediated by adrenocorticotropic hormone has a central role in the regulation of androgen synthesis. Serum adrenocorticotropic hormone and adrenal androgen concentrations were correlated with the posttreatment prostate specific antigen. Adrenocorticotropic hormone mediated androgen synthesis is a potential target for advanced androgen deprivation therapy.

Topics: Adrenocorticotropic Hormone; Aged; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Flutamide; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Diseases; Chemotherapy, Adjuvant; Cyproterone Acetate; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Fractures, Bone; Goserelin; Humans; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Neoplasm Staging; Patient Selection; Prostatic Neoplasms; Risk Assessment; Time Factors; Treatment Outcome

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Drug Prescriptions; Gonadotropin-Releasing Hormone; Goserelin; Health Resources; Humans; Leuprolide; Male; Medicare; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; SEER Program; United States

To evaluate the impact of neoadjuvant hormonal therapy on the permanent transperineal (125)I-seed brachytherapy for localized high-risk prostate cancer.. Ten patients with T(1)-T(2a) localized high-risk prostate cancer were reviewed. The mean level of PSA was (29.4 ± 12.6) µg/L (20 - 50 µg/L) and the mean prostate volume (54 ± 33) ml. All cases were sequentially treated on a neoadjuvant hormonal therapy with 1 week of Casodex (50 mg/d) and 3 - 10 months (median: 6 months) of Casodex (50 mg/d) with Zoladex (3.6 mg per 4 weeks, SC). Then all patients received the transperineal permanent interstitial (125)I-seed implantation brachytherapy by template method. The matched peripheral dose of seed implantation was 145 Gy (median number of (125)I seeds: 46), urethral peripheral dose ≤ 80 Gy and rectal peripheral dose ≤ 60 Gy. The mean operative duration was 1.75 hours (range: 1 - 2.5 hours).. After neoadjuvant hormonal therapy for 3 - 10 months, the PSA level decreased to (1.4 ± 0.7) µg/L in all patients. The mean prostate volume significantly decreased to (25 ± 10) ml (t-test, P < 0.01). The Foley tube extracted at Days 3 - 5 post-brachytherapy. Side effects of mild dysuria (n = 1) and urethral irritation (n = 1) were effectively managed by symptomatic treatment. After a median follow-up of 13 months (range: 3 - 24), the PSA level was (0.9 ± 0.7) µg/L.. A combination of neoadjuvant hormonal therapy with brachytherapy may lower the PSA level and shrink the prostate volume so as to ensure an effective dose in the target tumor and improve the therapeutic efficacy for localized high-risk prostate cancer.

Topics: Aged; Aged, 80 and over; Anilides; Antineoplastic Agents, Hormonal; Brachytherapy; Goserelin; Humans; Iodine Radioisotopes; Male; Neoadjuvant Therapy; Nitriles; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

We report the case of an 80-year-old man who presented with relapsing prostate cancer and cerebral metastases which showed evidence of radiological and clinical response to androgen suppression alone without additional whole brain radiotherapy.

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Agents, Hormonal; Brain Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease Progression; Goserelin; Humans; Male; Neoplasm Grading; Neoplasm Recurrence, Local; Prostatic Neoplasms; Tomography, X-Ray Computed; Transurethral Resection of Prostate

Side effects of cancer treatment have been found to have a significant impact on patients' psychological well-being. Each of the primary treatment options for prostate cancer is associated with significant side effects that can have a dramatic impact on quality of life. Hot flashes are a notable side effect of androgen deprivation therapy (ADT) and a potential source of distress due to their episodic nature and low frequency in a normal aging male population. The current study sought to examine the relationship between hot flashes and cancer-related distress during the first three months of ADT.. Participants were 68 men with various stages of prostate cancer scheduled to begin ADT for the first time. Study measures were completed at the beginning of treatment and 3 months later.. Repeated measures ANOVA indicated that men who did not experience hot flashes had a significant decrease in total cancer-related distress and avoidance over the 3-month period, while men with hot flashes exhibited no change in distress. Among men with hot flashes, results of hierarchical regression analyses indicated that a worse experience with hot flashes was a significant predictor of greater increases in intrusion and total cancer-related distress over the 3-month period.. These results suggest that hot flashes serve to maintain levels of distress during the treatment period. Further research should extend these findings by lengthening the follow-up period and using ecological momentary assessment to refine measurement of these constructs and provide evidence for the direction of causality between hot flashes and distress.

Topics: Adaptation, Psychological; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Goserelin; Hot Flashes; Humans; Injections, Intramuscular; Leuprolide; Male; Middle Aged; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Sick Role; Surveys and Questionnaires

The purpose of this study is to evaluate the therapeutic effect of radical prostatectomy combined with preoperative neoadjuvant hormonal ablation therapy for prostate cancer (PCa). In this study, a total of 31 patients with local PCa underwent radical prostatectomy; of these, 12 patients underwent preoperative hormonal deprivation with a combination of goserelin and flutamide for a period of 5.6 months. Data regarding clinical characteristics were compared between the neoadjuvant therapy and radical prostatectomy groups. A total of 31 patients received pelvic lymph node clearance, and the rate of positive lymph nodes was 12.9% (4/31). Serum prostate-specific antigen (PSA) was 8.9 +/- 1.2 microg L(-1) after the neoadjuvant therapy and 0.4 +/- 0.3 microg L(-1) one month after the radical prostatectomy. There were significant differences in the positive surgical margins, seminal vesicle invasion and lymph node metastasis between the neoadjuvant therapy group (n = 12) and the radical prostatectomy group (n = 19, P < 0.01). The resulsts indicates that preoperative hormonal deprivation induced by goserelin and flutamide can decrease clinical and pathological staging, but assessment of its influence on long-term prognosis requires further study.

Topics: Aged; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Dose-Response Relationship, Drug; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Treatment Outcome

Topics: Aged; Antineoplastic Agents, Hormonal; Behavior; Dementia; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms

To present oncological results with intermittent androgen deprivation (IAD) in a single center.. Between 1992 and 2008, 566 patients with prostate cancer (PC) were selected for a non-randomized study of IAD. Two hundred and eighteen patients had biochemical recurrence (BCR) after local treatment for PC and 348 patients had micro- or macro-metastatic disease. On-treatment period (ONTP) consisted of three-monthly injections of gonadatropin-releasing hormone (GnRH) agonist combined with daily oral androgen receptor antagonist. Off-treatment period (OFTP) was indicated when prostate-specific antigen (PSA) was <4 ng/ml. Criteria for resumption of hormonal therapy were PSA >20 ng/ml or clinical symptoms. Cancer specific survival curves were computed according to the Kaplan-Meier method.. Median follow-up was 81 months (12-230). Median age was 74.7 years (52-92). Median Gleason score at diagnosis was 7 (3-9). Median initial PSA was 17 ng/ml (0.4-433). Cycle duration decreased progressively from 23 months for the 1st cycle to 10 months at 12th cycle. The number of patients who became hormone resistant was 182 (32%). Median cancer specific survival probability for the series is 12 (10.8-infinity) years. No previous treatment group showed a higher cancer specific survival probability (log rank test, CI 95%, P = 0.003) versus BCR group. Multivariate analysis of cancer specific survival demonstrates age, initial Gleason score and initial PSA level as significant factors affecting mortality (P < 0.05).. Intermittent androgen deprivation is an acceptable treatment in different stages of PC. Duration of cycle decreased progressively during therapy. Age, Gleason score and PSA are factors predicting mortality.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Androgen Receptor Antagonists; Anilides; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Time Factors; Tosyl Compounds; Treatment Outcome

To evaluate the influence of patient- and treatment-related factors on freedom from biochemical failure (FFbF) in patients with intermediate-risk prostate cancer.. From a prospectively collected database of 2250 men treated at Mount Sinai Hospital from 1990 to 2004 with low-dose-rate brachytherapy for prostate cancer, 558 men with either one or more intermediate-risk features (prostate-specific antigen [PSA] level 10-20 ng/mL, Gleason score 7, or Stage T2b) were identified who had a minimum follow-up of 24 months and postimplant CT-based dosimetric analysis. Biologically effective dose (BED) values were calculated to compare doses from different isotopes and treatment regimens. Patients were treated with brachytherapy with or without hormone therapy and/or external-beam radiotherapy. Patient- and treatment-related factors were analyzed with respect to FFbF. The median follow-up was 60 months (range, 24-167 months). Biochemical failure was defined according to the Phoenix definition. Univariate analyses were used to determine whether any variable was predictive of FFbF. A two-sided p value of <0.05 was considered significant.. Overall, the actuarial FFbF at 10 years was 86%. Dose (BED <150 Gy(2) vs. >or=150 Gy(2)) was the only significant predictor of FFbF (p < 0.001). None of the other variables (PSA, external-beam radiotherapy, Gleason score, treatment type, hormones, stage, and number of risk factors) was found to be a statistically significant predictor of 10-year FFbF.. Radiation dose is an important predictor of FFbF in intermediate-risk prostate cancer. Treatment should continue to be individualized according to presenting disease characteristics until results from Radiation Therapy Oncology Group trial 0232 become available.

Topics: Analysis of Variance; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Biopsy; Brachytherapy; Flutamide; Follow-Up Studies; Goserelin; Humans; Iodine Radioisotopes; Leuprolide; Male; Nitriles; Palladium; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radioisotopes; Radiotherapy Dosage; Relative Biological Effectiveness; Tosyl Compounds; Treatment Failure

To evaluate the overall survival (OS) and disease-specific survival (DSS) in men receiving primary androgen-deprivation therapy (PADT) or salvage medical ADT (SADT) for prostate cancer.. After Institutional Review Board approval, we retrospectively reviewed patients receiving ADT for prostate cancer between July 1987 and June 2007. Variables included age at diagnosis and ADT induction, race, PSA level before ADT, ADT schedule (continuous/intermittent), clinical/pathological stage, hormone-refractory prostate cancer (HRCP) status, PADT or SADT, and deaths.. In all, 548 men were analysed. The mean age at diagnosis and ADT induction were 70.1 and 72.3 years, respectively, and 321 (58.6%) were African-American. The median PSA level before ADT was 16.3 ng/mL. ADT was administered continuously in 497 (90.7%) patients; 342 (62.4%) received PADT while 206 (37.6%) received SADT. At mean (range) follow-up of 81.8 (2.1-445) months, 98 (17.9%) deaths occurred; 31 (31.6%) were cancer-specific. The OS and DSS in the PADT and SADT groups were not significantly different (P = 0.36 and P = 0.81, respectively). Mortality rates/distributions were similar between groups (P = 0.68). Multivariate predictors of OS and DSS included age at diagnosis (P = 0.03) and ADT induction (P = 0.009), tumour stage (P < 0.001), and PSA level at ADT induction (P = 0.01). Progression to HRPC worsened OS and DSS (both P < 0.001).. PADT and SADT prolong survival in men with prostate cancer. HRPC portends a poor DSS. Age at diagnosis and ADT induction, PSA level before ADT, and disease stage predict both OS and DSS in this population. However, most men died from causes unrelated to prostate cancer, thus questioning the true value of ADT in prolonging patient survival.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cause of Death; Goserelin; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Retrospective Studies; Salvage Therapy; Survival Analysis; Treatment Outcome

Topics: Alcohol Drinking; Antineoplastic Agents, Hormonal; Ethanol; Goserelin; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radiation Injuries; Tomography, X-Ray Computed; Urinary Bladder

The beta1C integrin is an alternatively spliced variant of the beta1 integrin subfamily that at variance with its wild-type counterpart, i.e., the beta1A integrin, inhibits cell proliferation in prostate cancer cells. We have recently shown that transcriptional, translational and post-translational processes contribute to the selective loss of beta1C integrin during prostate malignant transformation. Here, we investigated whether androgen deprivation therapy (ADT) may affect beta1C mRNA expression in prostate cancer. Neoplastic prostates were obtained from patients undergoing radical prostatectomy who had received neoadjuvant ADT. The beta1C mRNA level was measured by Northern hybridization experiments and compared to normal prostates obtained from patients who underwent radical cystoprostatectomy for bladder cancer. Furthermore, the beta1C integrin gene transcriptional activity was measured by nuclear Run-on assays. We found an increase of beta1C mRNA expression (208+/-11%; p<0.01) in patients who received ADT in comparison to those who did not. Furthermore, we demonstrated an increase of gene transcriptional activity (360+/-10%; p<0.01) possibly partially or completely responsible for the regulation of the beta1C integrin mRNA levels. Short-term administration of ADT seems to interfere with beta1C integrin expression, suggesting the existence of androgen-mediated pathways involving beta1C. Precise characterization of the mechanisms that regulate the expression of this factor in cancer cells will provide further insight into the molecular mechanisms involved in tumor progression and possibly contribute to the identification of molecular targets for the development of new therapeutic strategies.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Blotting, Northern; Disease Progression; Gene Expression Regulation, Neoplastic; Goserelin; Humans; Integrin beta1; Male; Middle Aged; Nitriles; Prostatic Neoplasms; RNA, Messenger; Tosyl Compounds; Transcription, Genetic

We describe a patient with node positive prostate cancer treated with radiation, androgen deprivation, and immunotherapy with long-term overall survival and PSA control. ELISPOT immunoassay studies demonstrated PSA specific T-cells prior to starting vaccine therapy suggesting that this positive response may be related to an improved antitumor immune response of the patient, increased immunogenicity of the tumor, or decreased activation of immune escape pathways. Further evaluation of therapeutic cancer vaccines in combination with radiation and hormonal therapy in the definitive management of prostate cancer is warranted.

Topics: Adenocarcinoma; Anilides; Antineoplastic Agents, Hormonal; B7-1 Antigen; Cancer Vaccines; Goserelin; Humans; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Engineering; Radiography, Abdominal; Radiotherapy; T-Lymphocytes; Tosyl Compounds; Ultrasound, High-Intensity Focused, Transrectal; Vaccines, Synthetic

To explore whether the presence of occult disseminated tumor cells (DTCs) in the bone marrow before neoadjuvant hormone therapy influences the prognosis of patients with organ confined prostate cancer treated by radical prostatectomy.. Pretreatment bone marrow aspirates from 193 cT (1-4) pN0M0 prostate cancer patients submitted to neoadjuvant hormone therapy (mean, 8 months) followed by radical prostatectomy were immunohistochemically evaluated by anticytokeratin antibody A45-B/B3 previously validated for the detection of DTCs. Bone marrow status was compared with established clinical and histopathologic risk parameters. Patients' outcome was evaluated using prostate-specific antigen (PSA) blood serum measurements as surrogate marker for recurrence over a median follow-up of 44 months.. DTCs were detected in 44.6% of patients. Bone marrow status neither correlated with tumor grade and stage, nor with the pretreatment PSA risk category (all P values > .05). In the univariate Kaplan-Meier analysis, the presence of DTCs was a significant prognostic factor with respect to poor PSA progression-free survival (log-rank test P = .0035). Using a multivariable piecewise Cox regression model, the presence of DTCs was an independent predictor of PSA relapse (relative risk 1.82; P = .014).. The presence of DTCs in the bone marrow of patients with prostate cancer before neoadjuvant hormone therapy and subsequent surgery represents an independent prognostic parameter, suggesting that DTCs may contribute to the failure of current neoadjuvant hormone therapy regimens.

Topics: Aged; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Marrow Neoplasms; Chemotherapy, Adjuvant; Disease-Free Survival; Flutamide; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Multivariate Analysis; Neoadjuvant Therapy; Neoplastic Cells, Circulating; Nitriles; Prognosis; Prostatectomy; Prostatic Neoplasms; Tosyl Compounds

Haemoglobin levels often decline into the anaemic range with androgen deprivation therapy (ADT). We conducted a chart review of patients receiving ADT for metastatic prostate cancer to assess anaemia-related symptoms.. 135 stage IV prostate cancer cases were reviewed for treatment type; haemoglobin values before and after treatment; and symptoms of anaemia. Mean haemoglobin levels before and after for all treatment forms, for leuprolide alone, and for combination leuprolide/bicalutamide were calculated and evaluated for significant differences. The numbers of patients developing symptoms were recorded and the effects of specific therapies evaluated.. For all ADT treated patients, mean haemoglobin declined by -1.11 g/dL (p<.0001). Leuprolide-alone treated patients had a mean decline of -1.66 g/dL (p<0.0001). Leuprolide and bicalutamide combination treatment caused a mean decline of -0.78 g/dL (p=0.0426). 16 of 43 patients had anemia symptoms. Contingency analysis with Fisher's exact test shows patients receiving leuprolide therapy alone versus other forms of ADT were significantly less likely to have symptoms (chi(2)=0.0190).. The present study confirms that ADT results in a significant drop in haemoglobin levels into the anaemic range. A number of patients become symptomatic from this change. Practitioners should monitor haemoglobin levels, and treat symptomatic patients.

Topics: Aged; Androgen Antagonists; Anemia; Anilides; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Hemoglobins; Humans; Leuprolide; Linear Models; Male; Neoplasm Metastasis; Nitriles; Prostatic Neoplasms; Retrospective Studies; Tosyl Compounds

To compare the effects of leuprolide acetate and goserelin acetate for suppressing serum testosterone levels in Japanese patients with prostate cancer, as several recent studies suggested that serum testosterone is not always suppressed below the upper limit of the castration range in patients using luteinizing hormone-releasing hormone (LH-RH) agonists, especially leuprolide acetate.. In all, 232 patients with prostate cancer, whose serum testosterone levels were measured before and during treatment using a 1- or 3-monthly formulation of leuprolide or goserelin, were enrolled in a retrospective study. The mean age of the patients was 69.8 years and the mean testosterone level before the LHRH treatment was 4.54 ng/mL. The patients had their testosterone levels assessed a mean (range) of 5.4 (1-35) times during the LHRH treatment. A castrate serum testosterone level was defined as

Topics: Aged; Aged, 80 and over; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Testosterone; Treatment Outcome

Topics: Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms

The time to testosterone recovery after the cessation of androgen deprivation therapy appears to be dependent on the therapy duration. Most men will recover normal testosterone levels within 18 months according to the findings from studies that frequently involved fewer than 3 years of androgen deprivation therapy. Our goal was to assess the proportion of patients who remain castrated after cessation of longer duration luteinizing hormone-releasing hormone (LHRH) agonist therapy for prostate cancer.. We reviewed 15 patients who had received at least 48 months of continuous goserelin injection therapy for prostate cancer and had not been receiving the therapy for at least 18 months. The serum testosterone and prostate-specific antigen data were obtained.. The mean duration of LHRH agonist therapy was 73 months (range 48 to 110). At the cessation of therapy after a mean follow-up of 31 months, 53% had testosterone levels that remained castrated. Only 1 patient achieved normal testosterone levels. Of the patients with greater than castrate testosterone levels, 71% experienced a prostate-specific antigen rise. All the men with an intact prostate who had testosterone recovery to greater than castrate levels had a prostate-specific antigen increase, which might represent a return toward the pretreatment baseline. Of the patients who started therapy after age 70 years, 78% remained castrated versus 17% of those who started before 70 years.. Of the men who had received 4 or more years of LHRH agonist therapy for prostate cancer, 53% remained castrated up to 2.5 years after therapy cessation. Patients who started LHRH agonist therapy after age 70 were more likely to remain castrate after stopping long-term therapy.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Retrospective Studies; Testosterone; Time Factors

Topics: Aged; Antineoplastic Agents, Hormonal; Attitude of Health Personnel; Drug Implants; Drug Monitoring; Goserelin; Humans; Injections, Subcutaneous; Male; Nurse's Role; Nursing Evaluation Research; Nursing Methodology Research; Office Visits; Patient Education as Topic; Patient Satisfaction; Prostatic Neoplasms; Social Support; Surveys and Questionnaires; Time and Motion Studies

We determined penile length alterations in men treated with androgen suppression plus radiation therapy for local or locally advanced prostate cancer.. From November 2000 to November 2005, 47 patients were enrolled in this prospective study. After clinical staging all patients received hormonal therapy (luteinizing hormone releasing agonist, leuprolide acetate or goserelin every 3 months for a total of 3 injections) and at month 7 of hormonal therapy radiation therapy was begun (total 70 Gy) for 7 weeks. Stretched penile length measurements were performed before starting androgen suppression therapy and every 3 months thereafter with a paper ruler.. With the initiation of therapy a gradual decrease in stretched penile length was observed. Penile shortening was statistically significant at a mean followup of 18 months (mean 14.2 to 8.6 cm, p <0.001).. Our findings support observations of decreased penile length after neoadjuvant hormonal therapy plus external beam radiation therapy for local or locally advanced prostate cancer. Patients should be counseled before therapy that penile shortening may occur.

Topics: Aged; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Disease Progression; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Penis; Prospective Studies; Prostatic Neoplasms

Controversy and a notable paucity of published clinical data best characterize the current knowledge of testosterone-replacement therapy (TRT) for hypogonadism after treatment for early, localized prostate cancer. The objective of this study was to assess the risk of biochemical failure with TRT after treatment of early prostate cancer with permanent transperineal brachytherapy with or without external beam therapy in patients with low serum levels of testosterone and clinical symptoms of hypogonadism.. Patients who underwent prostate brachytherapy from 1996 to 2004 and received subsequent TRT for symptomatic hypogonadism were reviewed to detail cancer characteristics and treatment as well as pre- and post-TRT serum testosterone and prostate-specific antigen (PSA) values.. Thirty-one men received TRT after prostate brachytherapy for 0.5 to 8.5 years (median, 4.5 years), with a follow-up that ranged from 1.5 years to 9.0 years (median, 5.0 years) postbrachytherapy. TRT was started from 0.5 years to 4.5 years (median, 2.0 years) after brachytherapy. Serum total testosterone levels ranged from 30 ng/dL to 255 ng/dL (median, 188 ng/dL) before TRT and rose to 365 ng/dL to 1373 ng/dL (median, 498 ng/dL) on TRT. Transient rises in PSA were observed in 1 patient. The most recent PSA level was <0.1 ng/mL in 23 patients (74.2%), <0.5 ng/mL in 30 patients (96.7%), and <1 ng/mL in 31 patients (100%). No patients stopped TRT because of cancer recurrence or documented cancer progression.. For patients with low serum testosterone levels and symptoms of hypogonadism, TRT may be used with caution and close follow-up after prostate brachytherapy.

Topics: Aged; Antineoplastic Agents, Hormonal; Brachytherapy; Disease-Free Survival; Goserelin; Hormone Replacement Therapy; Humans; Hypogonadism; Leuprolide; Male; Middle Aged; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Outcome

To report a case of right posterior subcapsular cataract induced by 3-monthly depot luteinizing hormone-releasing hormone (LHRH) analogue therapy in a patient with early prostate cancer.. A 52-year-old male with static myopia of several years' duration was given a 3-month depot LHRH analogue (goserelin 10.8 mg) as part of neoadjuvant treatment for early prostate cancer. Four weeks after the treatment, the patient developed right posterior subcapsular cataract commonly associated with steroid treatment. The patient had right eye cataract extraction followed by insertion of a new lens.. This report shows a case of a posterior subcapsular cataract as an adverse reaction to depot goserelin acetate. This is a feature commonly seen in steroid-induced cataract. Patients with prostate cancer and poor vision if due to cataract may not be ideal patients for depot preparations of LHRH analogues.

Topics: Antineoplastic Agents, Hormonal; Cataract; Cataract Extraction; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms

An 87-year-old man visited our hospital, complaining of abdominal distention and inability to urinate. Computed tomography (CT) and magnetic resonance imaging revealed a giant prostate tumor. The patient underwent percutaneous tumor biopsies. The histologic diagnosis was moderately differentiated adenocarcinoma of prostate. The clinical stage according to the TNM classification system was T4N0M0, stage IV. Combined androgen blockade therapy was performed. Four months later, CT showed that the tumor had decreased markedly in size, and the serum prostate specific antigen level was within normal range. Hormone refractory prostate cancer was not found 1 year after the start of treatment.

Topics: Adenocarcinoma; Adrenergic alpha-Antagonists; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Chlormadinone Acetate; Drug Administration Schedule; Drug Therapy, Combination; Goserelin; Humans; Magnetic Resonance Imaging; Male; Naphthalenes; Nitriles; Piperazines; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds

Topics: Aged; Antineoplastic Agents, Hormonal; Attitude of Health Personnel; Drug Administration Schedule; Drug Implants; Education, Nursing, Continuing; Gonadotropin-Releasing Hormone; Goserelin; Health Services Needs and Demand; Humans; Injections, Subcutaneous; Male; Nurse's Role; Nursing Evaluation Research; Nursing Staff, Hospital; Pain; Patient Education as Topic; Prostatic Neoplasms; Surveys and Questionnaires

To elucidate the crucial predictors for prostate-specific antigen (PSA) trends and determine the usage of anti-androgen treatment during delayed-combined androgen blockade (CAB) leading to a PSA level below 0.2 ng/mL.. From January 2001 to December 2004, 105 prostate cancer patients were enrolled. Medical castration and anti-androgen treatment were used sequentially and termed delayed-CAB. The first goal was to maintain an undetectable PSA level. The nadir PSA was determined after medical castration only. Anti-androgen was given if a PSA level of more than 0.2 ng/mL was observed and the subsequent PSA response was assessed. All cases were divided into two groups based on whether the PSA was lower (n = 59) or higher (n = 46) than 0.2 ng/mL. An analysis of the difference between the two groups was calculated.. The median of the initial PSA level in the lower group was lower than in the higher group with a 95% cut-off level of 40 ng/mL. The median PSA half-life in the lower group was also reduced with a 95% cut-off of 3.6 months. In a multivariate analysis, the pretreatment PSA level and the PSA half-life exhibited a significant correlation between the two groups. Anti-androgen treatment was given to 26 cases in the higher group. The PSA increased in one case, decreased to less than 0.2 ng/mL in 17 cases and remained over 0.2 ng/mL in eight cases.. Both the PSA half-life and the pretreatment PSA level were useful markers for predicting the PSA trends to determine the optimal use of anti-androgen treatment during delayed-CAB.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Drug Therapy, Combination; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Nitriles; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

We analyzed clinical effects of flutamide as a second-line agent for maximum androgen blockade (MAB) in patients with relapsing prostate cancer who received bicalutamide as the first-line MAB agent. This study included 13 patients with progressive prostate cancer who had relapsed after first-line MAB, with bicalutamide at 80 mg/day. After checking for antiandrogen withdrawal syndrome, they were given flutamide at 375 mg/day as second-line MAB. The effectiveness of that therapy was evaluated by changes in prostatic specific antigen (PSA) levels, with response defined as a decrease of greater than 50% from the start of therapy. We also compared several factors between responders and non-responders. Nine (69.2%) of the 13 patients showed a decrease in PSA levels, of whom five (38.5%) had a greater than 50% decrease and were defined as responders. The median duration of PSA response was 11.0 months (range 5-20 months). Patients who had a longer duration of response to first-line MAB had a significantly greater response to second-line MAB. For advanced prostate cancer patients who progressed on first-line MAB with bicalutamide, flutamide administration as a second-line antiandrogen was found to be relatively effective, especially for those who showed a longer duration of response to the first-line MAB. Our results confirm previous findings that MAB using flutamide is an effective second-line hormonal therapy.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Biopsy, Needle; Drug Resistance, Neoplasm; Drug Therapy, Combination; Endosonography; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Tomography, X-Ray Computed; Tosyl Compounds; Treatment Outcome

Granulomas resulting from the administration of luteinizing hormone-releasing hormone analogues (LH-RH analogues) are thought to be very rare. We report on our clinical experience with injection-site granulomas that result from the administration of LH-RH analogues, and we evaluate the incidence rate of these granulomas.. We used the clinical records of 118 patients who were administered LH-RH analogues in 2005. We describe the clinical data of patients who experienced injection-site granulomas and evaluated the incidence rate.. Five patients demonstrated injection-site granulomas due to LH-RH analogue administration. The incidence rate was 4.2% (5 of 118 patients). Most of the granulomas occurred after the first or second administration of 11.25mg of leuprorelin acetate.. The occurrence of granulomas resulting from the administration of LH-RH analogues was thought to be very rare. Our study, however, revealed a higher incidence rate than expected, especially for leuprorelin acetate.

Topics: Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Antineoplastic Agents, Hormonal; CD3 Complex; Gonadotropin-Releasing Hormone; Goserelin; Granuloma; Humans; Injections, Subcutaneous; Leuprolide; Male; Prostatic Neoplasms

We investigated the change in dihydrotestosterone in the prostate during androgen deprivation therapy in connection with prostate cancer aggressiveness using the Gleason score.. A total of 28 patients with clinically localized prostate cancer who were treated with androgen deprivation therapy for 6 months were enrolled in this study. Dihydrotestosterone in the prostate and serum were analyzed using liquid chromatography/electrospray ionization-mass spectrometry after polar derivatization before and after androgen deprivation therapy.. The change in dihydrotestosterone during androgen deprivation therapy in the prostate with Gleason score 7 to 10 prostate cancer was significantly smaller than that in the prostate with Gleason score 6 or less (p = 0.016). There were no significant differences between patients with Gleason score 7 to 10 prostate cancer and patients with Gleason score 6 or less in dihydrotestosterone in the prostate, in serum androgens and in serum androgen ratios before and after androgen deprivation therapy.. Low dihydrotestosterone in the prostate is probably sufficient to propagate the growth of aggressive prostate cancer. Furthermore, the prostate with aggressive prostate cancer can produce androgens from adrenal precursors more autonomously than the prostate with nonaggressive prostate cancer under a low testosterone environment with testicular suppression.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Biomarkers, Tumor; Dihydrotestosterone; Disease Progression; Flutamide; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Orchiectomy; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

The authors evaluated whether the duration of androgen suppression (AS) after the completion of hormone therapy (HT) was associated with the risk of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM).. The study cohort was comprised of 220 men who received radiation therapy (RT) and 6 months of HT for prostate cancer between 1996 and 2005. The duration of AS was defined as the time to return to the baseline testosterone level after the completion of HT. Grays and Cox regression analyses were used to evaluate whether the duration of AS after the completion of HT was associated with the time to PCSM and ACM, respectively, after adjusting for known prognostic factors.. An increasing duration of AS was associated with a decreased risk of PCSM (adjusted hazards ratio [HR], 0.89; P = .003) and ACM (HR, 0.94; P = .007). Men who had prostate cancer with Gleason scores from 8 to 10 had significantly lower cumulative incidence estimates of PCSM (P = .04) if the duration of AS plus the length of HT administration was >/=2 years compared with <2 years. After a median follow-up of 6.1 years, the respective 5-year estimates were 0% and 38%.. The duration of AS after 6 months of HT was associated with the risk of PCSM and ACM. This duration could be used to identify men who have prostate cancer with Gleason scores from 8 to 10 in whom 6 months of HT produces long-term testosterone suppression, which may provide the cancer-specific survival benefit observed with long-term HT.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cohort Studies; Combined Modality Therapy; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Intensity-Modulated; Survival Rate; Time Factors; Treatment Outcome

Topics: Aftercare; Aged; Antineoplastic Agents, Hormonal; Carcinoma, Signet Ring Cell; Combined Modality Therapy; Goserelin; Humans; Male; Neoadjuvant Therapy; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Radiotherapy, Conformal

A 74-year-old male was treated with endocrine therapy for localized prostate cancer. After 25 months he complained of a swollen neck, and was diagnosed with prostate cancer with lymph node metastasis of neuroendocrine differentiation. Neuroendocrine differentiation without elevation of conventional tumor markers is rare during the initial recurrent course of localized prostate cancer.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Cell Differentiation; Goserelin; Humans; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds

Although injection-site granulomas caused by leuprorelin acetate have been reported, there have been no reports of granulomas caused by both leuprorelin acetate and goserelin acetate. An 81-year-old man presented with subcutaneous nodules of the abdominal wall and upper arm, where 11.25 mg of leuprorelin acetate had been injected for the treatment of prostate cancer. Because of these nodules, treatment was changed to goserelin acetate. Nevertheless, he presented with another subcutaneous nodule at the injection site. Histological examination showed that these nodules consisted of numerous giant cells that were CD3-positive T lymphocytes and CD68-positive histiocytes associated with granulomatous changes. The granulomas had likely been caused by delayed-type hypersensitivity to leuprorelin acetate injection. The granuloma that formed after goserelin acetate injection might thus have developed owing to the immunogenicity of the previous leuprorelin acetate injections. The patient underwent surgical castration. The present case suggests that both leuprorelin acetate and goserelin acetate can cause injection-site disorders.

Topics: Aged, 80 and over; Goserelin; Granuloma; Humans; Injections; Leuprolide; Male; Prostatic Neoplasms

Peritoneal carcinomatosis is a rare finding in metastatic prostate cancer. In the literature peritoneal carcinomatosis is usually reported in its final stages with multiple metastases. A single peritoneal carcinomatosis with no further metastases is a very rare finding.. We report the case of a 75-year-old patient with initial ischuria. A prostate cancer could be confirmed and the further diagnostics showed no metastasis. In a transperitoneal approach for laparoscopic pelvic lymphadenectomy a peritoneal carcinomatosis from prostate cancer was proven. A complete antiandrogen therapy was started and PSA decreased for more than 14 months to a stable level of < 1 microg/L.. An isolated peritoneal carcinomatosis from prostate cancer is a very rare finding. The complete antiandrogen therapy is effective.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Follow-Up Studies; Goserelin; Humans; Lymph Node Excision; Male; Nitriles; Peritoneal Neoplasms; Peritoneum; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors; Tosyl Compounds; Transurethral Resection of Prostate; Treatment Outcome

Based on the data of current status of endocrine therapy for prostate cancer registered in the Japan Study Group of Prostate Cancer (J-CaP), we conducted an analysis of primary androgen deprivation therapy (PADT) and an interim analysis of the prognosis.. Of the 26 272 cases registered in the server of J-CaP, the 19 409 cases initially receiving PADT were included in this study. The initial therapy was divided into eight categories according to its features.. Of the 19 409 patients, 1513 (7.8%) were given anti-androgen monotherapy, 955 patients (4.9%) surgical castration only, 1001 patients (5.2%) surgical castration + anti-androgen, 3015 patients (15.5%) LHRH monotherapy, 1658 patients (8.5%) LH-RH + short-term anti-androgen, 10 434 patients (53.8%) LH-RH + anti-androgen, 37 patients (0.2%) watchful waiting and 796 patients (4.1%) other therapy. In progression-free survival, the prognosis was slightly better following maximum androgen blockade (MAB) in each stage.. The pattern of PADT is more typical in Japan compared with that in the United States. Patients who received MAB accounted for 59.0% of all the patients. MAB tends to be more often selected for patients who are rated as being at high risk on the basis of high Gleason score or PSA level upon diagnosis in each clinical stage of the disease. Investigations of the outcome are on-going and they will make clear the significance of this trend in Japan.

Topics: Aged; Aged, 80 and over; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Diethylstilbestrol; Disease-Free Survival; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Longitudinal Studies; Male; Middle Aged; Neoplasm Staging; Nitriles; Orchiectomy; Prognosis; Prostatic Neoplasms; Tosyl Compounds

Luteinizing hormone-releasing hormone agonist (LH-RH analogue) therapy, is one of the most widely used hormonal therapies. Recently, subcutaneous injection of a new long acting 3-month LHRH analogue depot has been developed. We investigated the adverse events induced by injection of an LH-RH analogue in 82 patients (median age was 75 year old, 59-87) using our questionnaire. Forty-eight and 34 cases had been administered leuprorelin acetate (LSR) and goserelin acetate (ZLA). The presentation rate of skin reaction was 8.8% (3/34) in the ZLA group and 14.6% (7/48) in the LSR group. There was no significant difference in rate of skin reaction between the LSR and ZLA group (p = 0.5113). Eight patients had induration (6 in LSR 2 in ZLA). We also present a case of subcutaneous granuloma formation at the injection site after using the three-month type preparation of leuprorelin acetate. We should be aware of the risk of skin reactions at the injection site and monitor carefully when using an LH-RH analogue.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Granuloma; Humans; Injections, Subcutaneous; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Skin

Prostate cancer (PCa) is the most commonly diagnosed cancer in American men with a subset inevitably presenting with metastatic disease to the bone. A well-recognized limitation in evaluating new treatments for metastatic PCa is the inability to use imaging to objectively assess response therapy. In this study, we evaluated the feasibility of clinically translating the functional diffusion map (fDM) imaging biomarker for quantifying the spatiotemporal effects of bone tumor response in a patient treated for metastatic PCa with bone metastases. A patient beginning therapy was scanned using MRI before treatment and again at 2 and 8 weeks post-treatment initiation to quantify changes in tumor diffusion values. Three metastatic lesions were identified for fDM analysis, all of which all demonstrated an early increase in diffusion values at 2 weeks, which increased further at 8 weeks post-treatment initiation. This finding correlated with a decrease in the patient's prostate-specific antigen (PSA) levels suggestive of patient response. CT, bone scans, and anatomic MRI images obtained posttreatment were found to be uninformative for the assessment of treatment effectiveness. This study presents the feasibility of fDM-measurements in osseous lesions over time and shows that changes in fDM values were consistent with therapeutic response. Thus, the fDM imaging biomarker may provide a quantifiable therapeutic endpoint to assess response in patients with metastatic bone cancer.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Body Water; Bone Neoplasms; Cell Membrane Permeability; Diffusion Magnetic Resonance Imaging; Feasibility Studies; Goserelin; Humans; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Tomography, X-Ray Computed; Tosyl Compounds; Treatment Outcome; Whole Body Imaging

Unlike goserelin, leuprorelin and triptorelin have not been assessed for their impact on survival in patients with locally advanced prostate cancer. The main adverse effects of these two drugs are similar, but convenience of use differs.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Castration; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Treatment Outcome; Triptorelin Pamoate

In Radiation Therapy Oncology Group (RTOG) trial 92-02, after men received neoadjuvant hormone cytoreduction and radiotherapy for locally advanced prostate carcinoma, they were randomized to receive either 2 years of long-term androgen-deprivation (LTAD) or no further treatment (short-term androgen-deprivation [STAD]). The specific objective of the current study was to determine whether LTAD was a cost-effective treatment for patients with locally advanced prostate carcinoma.. The cost-effectiveness of LTAD was tested using a Markov model that was designed using proprietary software. The analysis took a payor's perspective. Unit costs were obtained by estimation using a global Medicare fee schedule. Costs and outcomes were discounted by 3%. Distributions were sampled at random from the treatment utilities, transition probabilities, and costs using a second-order Monte Carlo simulation technique.. The expected mean cost was 32,564 dollars for LTAD compared with 33,039 dollars for STAD after accounting for the additional cost of salvage treatment for men who were treated with STAD. The mean number of quality-adjusted life years (QALYs) for men who received LTAD was 4.13 QALYs compared with a mean of 3.68 QALYs for men who received STAD. The cost-effectiveness acceptability curve analysis showed a 91% probability that LTAD was cost-effective compared with STAD. Although overall survival was similar in the LTAD and STAD groups, the patients who received LTAD experienced gains in QALYs and had lower costs, because LTAD prevented biochemical failure and the necessitating salvage hormone therapy.. The current analysis showed that LTAD was cost-effective for the entire population studied in RTOG trial 92-02.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Cost-Benefit Analysis; Flutamide; Goserelin; Humans; Male; Markov Chains; Monte Carlo Method; Neoadjuvant Therapy; Prostatic Neoplasms; Quality-Adjusted Life Years; Radiotherapy, Conformal; Randomized Controlled Trials as Topic

We assessed the relationship between GnRH agonists and the risk of clinical fractures in men with prostate cancer.. Using a database of medical claims from 16 large American companies we identified a study group of 3,779 men with prostate cancer who received treatment with a GnRH agonist and a control group of 8,341 with prostate cancer who were not treated with a GnRH agonist. Men with 1 or more medical claims for bone metastases were excluded. The rates of any clinical fracture, hip fracture and vertebral fracture were compared between the groups.. The rate of any fracture was 7.91/100 vs 6.55/100 person-years at risk in men who received vs did not receive a GnRH agonist (relative risk 1.21, 95% CI 1.09 to 1.34). The rates of hip fracture (relative risk 1.76, 95% CI 1.33 to 2.33) and vertebral fracture (relative risk 1.18, 95% CI 0.94 to 1.48) were also higher in men who received a GnRH agonist. GnRH agonist treatment was independently associated with fracture risk on multivariate analyses.. GnRH agonists increase the risk of clinical fracture in men with prostate cancer.

Topics: Aged; Aged, 80 and over; Fractures, Spontaneous; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Triptorelin Pamoate

The number of CAG repeats on the androgen receptor (AR) gene is inversely proportional to transcriptional activity. The purpose of this study was to determine if short-term androgen deprivation therapy (RT + HT) can improve outcome in patients with tumors with short CAG repeats (<19).. Prostate cancer patients were randomized to receive either radiotherapy (RT) alone or (RT + HT) in the RTOG 86-10 study. CAG repeats were measured in 94 tumor specimens (21%; test cohort) of the 456 (parent cohort) analyzable cases. AR flow cytometry measurements were done on 13 patients. The effect on local failure (LF), distant metastases (DM), prostate cancer survival (PSS), and overall survival (OS) was studied.. Pretreatment characteristics and assigned treatment arm were not significantly different between the parent and test groups except for a significantly higher risk of death (P = 0.049) in the test group. The median CAG repeat was 19. There were no significant differences in stage, or Gleason score between high (19 or greater) and low CAG (<19) patients within each treatment group. Number of CAG repeats alone did not significantly influence LF, DM, PSS, and OS. However, when the CAG repeat outcome was studied in conjunction with androgen deprivation therapy, patients with CAG <19 who received H + RT had improved local control as compared with patients who received RT alone (P = 0.026, 5-year rates 4.6% versus 36.4%) and improved local control over patients with CAG > or =19 that received H + RT (P = 0.028).. Patients with short CAG repeats show a local control benefit with short-term androgen deprivation therapy, but no improvement in survival.

Topics: Androgen Antagonists; Combined Modality Therapy; Flow Cytometry; Goserelin; Humans; Male; Prognosis; Prostatic Neoplasms; Receptors, Androgen; Survival Analysis; Treatment Outcome; Trinucleotide Repeats

To prospectively evaluate the time-course of recovery of serum testosterone levels after a short course of luteinizing hormone-releasing hormone analogue (LHRHa) and radical radiotherapy to the prostate.. Testosterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were sequentially measured prospectively in 59 men who received short-course LHRHa treatment and radiotherapy for localized prostate cancer. Measurements were made before treatment (baseline), during LHRHa treatment, and at 6, 12, 18, 24 and >40 weeks after the last LHRHa injection.. The median (range) time from the first to last LHRHa injection was 116 (54-194) days. The mean (95% confidence interval) testosterone levels (in nmol/L) at baseline, during treatment and at 6, 12, 18, 24 and >40 weeks afterward were 12.0 (10.8-13.1), 0.6 (0.5-0.7), 1.4 (0.6-2.2), 11.4 (9.7-13), 12.2 (10.5-14), 10.4 (8.9-12) and 11.7 (10.5-13). Four men had low baseline testosterone levels (<6.1 nmol/L). At 6 weeks after the last LHRHa injection, no men had testosterone levels in the 'normal' range; 35% were in the normal range at 12 weeks, 85% at 18 weeks, 89% at 24 weeks, and 96% at 1 year.. After LHRHa treatment and radiotherapy, the testosterone levels of most men had recovered to normal by 18-24 weeks after the last LHRHa injection.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Follicle Stimulating Hormone; Goserelin; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Prospective Studies; Prostatic Neoplasms; Testosterone; Treatment Outcome

We describe a patient with advanced prostate cancer who failed to achieve testosterone suppression with depot leuprolide after developing sterile abscesses at the injection sites. When the patient was switched to depot goserelin, he did not have any evidence of inflammation at the injection sites, but testosterone suppression again failed. This case suggests variable mechanisms for failure of gonadotropin-releasing hormone agonist therapy and highlights the necessity of prospective testosterone monitoring in patients who have developed sterile abscesses, even if switched to another gonadotropin-releasing hormone agonist.

Topics: Abscess; Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Bone Neoplasms; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Nitriles; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Tosyl Compounds; Treatment Failure

The antiproliferative effects of pharmacological agents used for androgen ablative therapy in prostate cancer, including goserelin, bicalutamide and cyproterone acetate (Fluka Chemie, Buchs, Switzerland), were tested in vitro. It was determined whether they affected prostate specific antigen mRNA and protein expression independent of growth inhibition.. Goserelin, bicalutamide (AstraZeneca, Zug, Switzerland) and cyproterone acetate were added to prostate specific antigen expressing, androgen dependent LNCaP and androgen independent C4-2 cell line (Urocor, Oklahoma City, Oklahoma) cultures. Proliferation was determined by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide assay (Roche, Mannheim, Germany). Prostate specific antigen mRNA expression was assessed by quantitative real-time polymerase chain reaction. Secreted prostate specific antigen protein levels were quantified by microparticle enzyme-immunoassay.. Goserelin inhibited cell growth and prostate specific antigen protein secretion in LNCaP and C4-2 cells. Prostate specific antigen mRNA expression was not decreased. Bicalutamide did not affect cell growth or prostate specific antigen mRNA expression in LNCaP or C4-2 cells, although it significantly decreased prostate specific antigen protein secretion in LNCaP and to a lesser extent in C4-2 cells. Cyproterone acetate decreased the growth of C4-2 but not of LNCaP cells. It did not affect prostate specific antigen mRNA or protein expression in either cell line.. Prostate specific antigen expression does not necessarily correlate with cell growth. Without a substantial effect on cell growth bicalutamide lowers prostate specific antigen synthesis, whereas cyproterone acetate decreases cell growth with no effect on prostate specific antigen secretion. Prostate specific antigen expression may be influenced by growth inhibition but also by altered mRNA and protein levels depending on the agent, its concentration and the cell line evaluated. For interpreting clinical trials prostate specific antigen is not necessarily a surrogate end point marker for a treatment effect on prostate cancer cell growth.

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cyproterone Acetate; DNA, Complementary; Goserelin; Humans; Male; Nitriles; Polymerase Chain Reaction; Prostate-Specific Antigen; Prostatic Neoplasms; RNA, Messenger; Tosyl Compounds

The objective of this study was to evaluate the therapeutic significance of a longer duration of neoadjuvant hormonal therapy (NHT) followed by radical prostatectomy (RP) in Japanese men with high-risk prostate cancer.. This study included a total of 42 patients with high-risk prostate cancer who were treated with NHT for >or=8 months prior to RP. In this series high-risk prostate cancer was defined as clinical stage T2c or T3, pretreatment serum prostate-specific antigen (PSA) >20 ng/ml and/or a biopsy Gleason score of 8-10. Biochemical recurrence was defined as a serum PSA level of >or=0.2 ng/ml. The data of these patients were retrospectively reviewed to clarify the relationships between treatment outcomes and various clinicopathological parameters.. The clinical stage was T2c in 13 patients and T3 in 29, the median value of pretreatment serum PSA was 43.3 ng/ml (range 9.7-322.2), and the biopsy Gleason score was 6 in 3 patients, 7 in 16 and >or=8 in 23. Following NHT (median 12 months, range 8-27), the median value of serum PSA decreased to 0.05 ng/ml (<0.01-18.3 ng/ml), and 15 patients (35.7%) were pathologically downstaged. During the median follow-up of 38 months (range 8-58), 11 patients (26.2%) developed biochemical recurrence, and the multivariate analysis identified pretreatment serum PSA, biopsy Gleason score and percentage of positive biopsy core as independent predictors of biochemical recurrence. The 3-year biochemical recurrence-free survival rate of the 42 patients was 68.3%, which was not significantly different from that of 34 patients who underwent RP for high-risk prostate cancer without NHT during the same period.. A longer duration of NHT followed by RP for patients with high-risk prostate cancer resulted in a comparatively favorable outcome. However, despite the nonrandomized retrospective analysis, the present findings suggest no significant impact of long-term NHT on biochemical recurrence. Longer follow-up is needed to determine whether this therapeutic strategy is beneficial for high-risk prostate cancer patients.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Japan; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Nitriles; Preoperative Care; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Risk Factors; Time Factors; Tosyl Compounds

To prospectively assess the efficacy and tolerability of bicalutamide monotherapy on biochemical failure of localized prostate cancer following total androgen deprivation (TAD) and 3D-conformal radiotherapy (3D-CRT).. Between January 1998 and January 2002, we prospectively evaluated 20 eligible patients with biochemical failure. All patients were initially treated with neoadjuvant TAD of 12 weeks before 3D-CRT (73.6 Gy at isocenter) and same regimen of TAD after completion of radiotherapy for 24 weeks in high-risk patients. We prescribed 150 mg/day bicalutamide monotherapy for 24 weeks in patients with biochemical failure according to American Society for Therapeutic Radiology and Oncology 1997 consensus definition. Primary end points were biochemical control (BC) and metastasis-free survival (MFS).. Median follow-up was 28 months after biochemical failure date. At last visit, the median PSA level of all patients was 2.80 ng/dl while 1.28 ng/dl for nonmetastatic and 30.7 ng/dl for metastatic patients. BC was successfully obtained in five of them with only bicalutamide. Ten patients developed distant metastasis among 15 patients receiving salvage TAD. MFS was 55% at three years for all 20 patients. Temporary gynecomasty was observed in 11 patients as the only serious toxicity.. Bicalutamide monotherapy seems to be a tolerable regimen for patients with biochemical failure following 3D-CRT, and TAD and may be effective in patients with low PSA levels at biochemical failure.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Disease Progression; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Nitriles; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Tosyl Compounds; Triptorelin Pamoate

Topics: Aged; Antineoplastic Agents, Hormonal; Atrophy; Disease Progression; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testis; Testosterone; Treatment Failure

To analyze post-androgen depletion (AD) primary tumors to identify markers of treatment failure because AD does not reduce the probability of prostate-specific antigen (PSA) failure after prostatectomy.. Tumors removed by radical prostatectomy after 3 months of AD from 21 patients were analyzed for gene expression using oligonucleotide arrays. Differences between patients with and without relapse were identified using a conservative significance criteria of a threefold change and delta 0.68, ensuring a false discovery rate of less than 11%.. At 50 months of follow-up, 7 of the 18 evaluable patients developed a biochemical recurrence. Gleason grade, pretherapy PSA level, T stage, and margin status were similar between the two groups. Patients with recurrence had greater post-AD PSA levels than those without recurrence (0.87 versus 0.19 ng/mL; P = 0.042). Gene expression analysis revealed 35 probe sets overexpressed in tumors from patients who relapsed. Among the highest ranked probe sets were PSA and other androgen-responsive genes. Serum PSA values during AD revealed similar findings. After 40 days of AD, the PSA level in those without recurrence was 1.21 ng/mL versus 4.5 ng/mL in those with recurrence (P = 0.0034). Immunohistochemistry of post-AD tumors also demonstrated a high PSA staining intensity in many tumors that recurred relative to those that didn't.. The results of our study show that early recurrence is associated with expression of androgen-responsive genes. Surprisingly, these could be identified as early as 3 months after the initiation of AD therapy. Whether this represents a failure to abrogate androgen receptor mediated signaling with androgen depletion or early reactivation of signaling is under study.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Flutamide; Gene Expression; Gene Expression Profiling; Goserelin; Humans; Male; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Predictive Value of Tests; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Treatment Failure

LHRH analogs have become a promising modality in prostate cancer therapy as an alternative to surgical castration, and the use of these agents is generally considered to be safe. Since now, only few cases of an apoplexy of previously undiagnosed pituitary adenoma (usually gonadotropinoma) at the beginning of therapy have been described in the medical literature. We present a case of a 74 year old patient who was diagnosed of prostate cancer at the age of 68. There was no evidence of metastatic disease. Radical prostatectomy was performed and LHRH analog gosereline (Zoladex 3.6 mg s.c.) was administered. During the first day after gosereline injection the patient developed headaches that became more severe over the next 3 days. Then the patient experienced nausea and vomiting, double vision and eyelid ptosis. On the 5th day the patient temporarily lost consciousness and was admitted to hospital. Imaging (computerized tomography, magnetic resonance imaging) revealed the presence of a pituitary tumor and hemorrhage within the gland. There was no evidence of pituitary dysfunction in hormonal studies. Neurosurgical intervention was postponed for 5 days after admission. Pathological mass with signs of recent hemorrhage was removed via transsphenoidal route. The tumor had negative immunohistochemical GH, ACTH and PRL staining. Neurological impairment resolved within 9 months after the operation. As a result the patient required adrenal and thyroid replacement. During 6 years of follow-up there was no evidence of prostate cancer recurrence.

Topics: Adenoma; Aged; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Neoplasms, Multiple Primary; Pituitary Apoplexy; Pituitary Neoplasms; Prostatic Neoplasms

The changes in serum prostate specific antigen (PSA) concentrations can be used as a prognostic factor in patients undergoing maximum androgen blockade for metastatic prostate cancer.. A total of 149 patients followed up in our department were classified into 4 groups on the basis of PSA changes: group 1; those with normalisation of PSA levels within the first 3 months, group 2; those with normalisation PSA between months 3 and 6, group 3; those with a decrease in PSA but not reaching normal range, group 4; those with no decrease. The gleason scores and the number of bone metastases were also compared between the groups.. The time to progression was significantly delayed in group 1 (mean: 23.3 months) compared to those with group 2 (mean: 16.9 months) (P<0.02). The time to progression in group 3 (mean: 8.45 months) was significantly shorter compared to the first two groups (P<0.001). Also, in patients with gleason scores 5-7 (grades 2) and gleason scores over 7 (grade 3) and group 1, the time to progression (mean: 21.2 months) was significantly delayed compared to those with the same gleason scores but with group 2 (mean: 13.4 months) (P<0.001).. The decrease in PSA level is more important than gleason scores in determining the time to progression. Early normalisation of PSA delays the time to progression, and when combined with gleason scores, PSA is an important prognostic factor in predicting the success of the therapy.

Topics: Aged; Antineoplastic Agents, Hormonal; Goserelin; Humans; Leuprolide; Male; Middle Aged; Monitoring, Physiologic; Neoplasm Metastasis; Orchiectomy; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies

Androgen deprivation therapy (ADT) is a strong risk factor for osteoporosis. The current study identified physician practices in preventing or treating osteoporosis during ADT. The practices of interest are the uses of dual-energy X-ray absorptiometry (DXA) scans, bisphosphonates, calcium or vitamin D supplement, calcitonin, or estrogen.. A retrospective medical record review was conducted. Patients were included if they had received ADT with goserelin injection for >/= 1 year. Multivariable logistic regression analysis was performed to identify independent predictors of receiving at least one intervention.. Analyses included 184 patients. Most were the elderly with multiple risk factors for osteoporosis. Only 8.7% (95% confidence interval [CI], 4.6-13.0%) of patients received a DXA scan at least once during the past 3 years. Oral and intravenous bisphosphonates were prescribed in 4.9% (95%CI, 1.8-8.0%) and 0.5% (95%CI, 0-2.0%) of patients, respectively, during the past year. Overall, 14.7% of patients (95%CI, 9.5-20.0%) received at least one intervention. Concurrent risk factors for osteoporosis, including smoking, alcoholism, advanced age, low body mass index, long duration of ADT, multiple comorbidities, history of fractures, and steroid use, were not independent predictors of having received interventions. However, bone metastasis was, with a hazard ratio of 5.6 (95%CI, 1.99-15.6%). Primary care physicians provided the greatest number of interventions and cancer-related specialists provided the fewest.. The majority of patients with prostate carcinoma undergoing ADT did not receive interventions to prevent or treat osteoporosis. Having other concurrent risk factors for osteoporosis was not predictive of receiving these few interventions.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Androgen Antagonists; Attitude of Health Personnel; Bone Density; Confidence Intervals; Diphosphonates; Drug Utilization; Follow-Up Studies; Goserelin; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Osteoporosis; Practice Patterns, Physicians'; Probability; Prognosis; Proportional Hazards Models; Prostatic Neoplasms; Retrospective Studies; Risk Assessment; Severity of Illness Index; Treatment Outcome

To investigate the rate of testosterone recovery and changes in bone mineral density in patients found to be osteoporotic while receiving luteinizing hormone-releasing hormone (LHRH) analogues after changing to antiandrogen monotherapy in an attempt to reduce further demineralization.. Fifteen patients receiving LHRH analogue therapy for > or = 1 year were identified as osteoporotic by distal forearm dual X-ray densitometry. They were then converted to antiandrogen monotherapy, and prostate specific-antigen (PSA) and total testosterone monitored at 3-monthly intervals. The forearm densitometry was repeated at 1 year.. All patients had some testosterone recovery; the mean (range) duration to initial detectable testosterone was 12.8 (6-22) months. Six patients had a normal testosterone level after a mean of 17.5 (14-30) months. In the year after stopping LHRH analogue therapy the mean bone mineral density (t-score) decreased by 7.2%.. Osteoporotic patients, after stopping LHRH analogues, continue to have suppressed levels of testosterone which have a detrimental effect on bone mineral density. We therefore would not advocate conversion to antiandrogen monotherapy to improve bone density, and suggest alternative therapeutic intervention e.g. bisphosphonate therapy, for these patients.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Density; Goserelin; Humans; Male; Middle Aged; Osteoporosis; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Many patients with localised prostate cancer present with symptoms of benign prostatic hypertrophy (BPH) and require neoadjuvant hormone therapy to shrink the gland before brachytherapy. The impact of this hormone therapy has been evaluated in 667 patients treated with Iodine seed monotherapy.. Prospective data from 667 patients treated between 1995 and 2001 by I-125 seeds prostate implant as monotherapy were analysed. The mean age was 63 years (42--77 years). Three hundred and forty-six (51.9%) patients had a short course of neo adjuvant hormone therapy and 321 (49.1%) did not. The prescribed minimum peripheral dose was 145 Gy (TG 43). Patients were followed up to a maximum of 8.2 years and a minimum of 18 months. Statistical analysis was performed to identify factors that would predict PSA relapse-free survival (PSA-RFS) defined by the American Society for Therapeutic Radiology and Oncology (ASTRO).. Overall the PSA relapse-free survival is 76.1 and 72.6% for patient cohorts being on pre-treatment hormones and not, respectively (P=0.107). Subdivided into risk groups the low risk group showed 92.5% PSA-RFS with hormones and 75.1% without (P=0.327). The intermediate group 75.7% with hormones and 72.9% without (P=0.148) and for the high-risk group 51.1% with and 51.1% without hormones (P=0.942). Evaluation of post-implant dosimetry in patients with and without hormone therapy showed that the D90 for those who received hormone therapy was 130.8 Gy compared with 145.1 Gy for those who did not (P<0.001). This may be related to the degree of oedema at the time of post-implant dosimetry. The CT to ultrasound prostate volume ratio was 1.17 for patients who received hormone therapy and 0.98 for those who did not (P<0.001). It is suggested that in the interval between stopping hormone therapy and doing post-implant dosimetry there was an increase in prostate volume, which results in a lower D90. Significant correlation was found between D90 and prostate volume on post-implant CT dosimetry with higher D90s for small volume prostates (P<0.001).. Overall hormone therapy had no significant effect on outcome. The apparent lower D90 in hormone treated patients may be related to a change in volume between pre-implant and post-implant dosimetry.

Topics: Adult; Aged; Anilides; Brachytherapy; Goserelin; Humans; Iodine Radioisotopes; Male; Middle Aged; Nitriles; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Tosyl Compounds

To assess the factors effecting PSA bounce and to identify any possible relationship with biochemical control after 3-D conformal radiotherapy (3D-CRT) and total androgen deprivation (TAD) for prostate cancer by evaluating four previously described PSA bounce definitions.. Between January 1998 and January 2001, 83 consecutive patients with clinically localized prostate cancer were treated by 3D-CRT with neoadjuvant 3 months and/or 6 months adjuvant TAD. All patients had a pretreatment PSA level, at least eight post-external beam radiotherapy (EBRT) PSA and testosterone levels and minimum two years of follow-up. Total radiotherapy dose was 73.6 Gy at ICRU reference point. Four previous definitions of PSA bounce were used: Critz definition (>or=0.1 ng/mL), Cavanagh definition (>or=0.2 ng/mL), Hanlon definition (>or=0.4 ng/mL) and Rosser definition (>or=0.5 ng/mL) according to original methodology performed to report PSA bounce. Biochemical failure was defined in accordance with the ASTRO consensus guidelines.. The median follow-up time was 40 months. PSA bounce was recorded as follows: Critz definition, 33 patients (40%); Cavanagh definition, 21 patients (25%); Hanlon definition, 11 patients (13%); and Rosser definition, 7 patients (8%). In multivariate analysis, pre-EBRT PSA level and the duration of TAD for Critz definition; age, pre-EBRT PSA and the duration of TAD for Cavanagh definition; age and duration of TAD for Hanlon definition; age and pre-biopsy PSA for Rosser definition were significant independent prognostic factors determining PSA bounce. A significant increase of mean testosterone level in bouncers was detected at the 6th-9th and 18th-21st months. PSA bounce did not predict for PSA failure in multivariate analysis.. We observed no correlation between biochemical failure and PSA bounce. The longer duration of TAD and older age were found to be inversely proportional with PSA bouncing in this cohort. Notably, recovery of testosterone might cause PSA bouncing.

Topics: Adenocarcinoma; Aged; Androgens; Antineoplastic Agents, Hormonal; Disease Progression; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Adjuvant; Radiotherapy, Conformal; Regression Analysis; Retrospective Studies; Testosterone; Time Factors; Treatment Outcome; Triptorelin Pamoate

To analyze the impact of neoadjuvant hormone therapy (HT) on acute gastrointestinal (GI) and genitourinary (GU) toxicity from radiotherapy (RT).. The toxicity rates of 480 consecutive prostate cancer patients were reviewed and compared using the chi2 test. Ordered logit regression analyses were performed including the major demographic, disease, and treatment factors. Although no reduction in acute GI toxicity from HT use was observed (P=0.067), a lower rate of acute GU toxicity was observed (P=0.002). No factor reached statistical significance on regression analysis.. Observed toxicity rates were similar or lower in patients receiving HT. Thus, increased RT toxicity should not be a concern when deciding to add neoadjuvant HT to RT for prostate cancer.

Topics: Aged; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Brachytherapy; Cohort Studies; Flutamide; Gastrointestinal Tract; Goserelin; Hormones; Humans; Leuprolide; Male; Middle Aged; Nitriles; Prognosis; Prostatic Neoplasms; Radiation Injuries; Radiotherapy; Radiotherapy Dosage; Regression Analysis; Testosterone; Time Factors; Tosyl Compounds; Treatment Outcome; Urogenital System

To analyze the impact of hormonal therapy (HT) on late gastrointestinal (GI) and genitourinary (GU) toxicity from external beam radiotherapy (RT).. The records of 445 consecutive patients with prostate cancer undergoing RT with or without HT were reviewed. Late toxicity rates, using established toxicity scoring guidelines, were tabulated in the two groups and compared using the chi-square test. Ordered logit regression analyses were performed that included the major demographic, disease, and treatment factors.. The chi-square analyses demonstrated lower rates of GI toxicity (P = 0.013) and GU toxicity (P = 0.041) in the cohort receiving HT; this reduction in toxicity appeared to be consistent across different toxicity grades. However, on regression analysis, the only factor reaching statistical significance in predicting late GI and late GU toxicity was the radiation dose (P = 0.004 and P = 0.047, respectively). In particular, on regression analysis, HT did not reach statistical significance in predicting late GI toxicity (P = 0.229) or late GU toxicity (P = 0.910).. Observed late RT toxicity rates were generally similar in patients who did and did not receive HT. Thus, increased late RT toxicity should not be a major concern when deciding to add HT to RT for treatment of localized prostate cancer.

Topics: Aged; Anilides; Antineoplastic Agents, Hormonal; Flutamide; Gastrointestinal Diseases; Goserelin; Humans; Leuprolide; Male; Male Urogenital Diseases; Nitriles; Prostatic Neoplasms; Radiation Injuries; Time Factors; Tosyl Compounds

To compare several characteristics of alternative definitions of biochemical failure (BF) in men with extended follow-up after radiotherapy (RT) with or with androgen deprivation therapy (ADT) for prostate cancer.. From December 1, 1991, to April 30, 1998, 688 men with Stage T1c-T3NX-N0M0 prostate cancer received RT alone (n = 586) or RT plus ADT (n = 102) with a minimal follow-up of 4 years and five or more "ADT-free" posttreatment prostate-specific antigen levels. BF was defined by three methods: (1) the ASTRO definition (three consecutive rises in prostate-specific antigen level); (2) a modified American Society for Therapeutic Radiology Oncology (ASTRO) definition requiring two additional consecutive rises when a decline immediately subsequent to three consecutive rises occurred; and (3) the "Houston" or nadir plus 2-ng/mL definition (a rise of at least 2 ng/mL greater than the nadir). The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy were determined for each using clinical progression as the endpoint. Furthermore, the misclassification rates for a steadily rising prostate-specific antigen level, ability to satisfy the proportional hazards (RT with or without ADT), effects of short follow-up, and intervals to the diagnosis of BF were compared.. The misclassification rate for BF using the nadir plus 2-ng/mL definition was 2% for RT alone and 0% for RT plus ADT compared with 0% and 0% for the modified ASTRO definition, and 5% and 23% for the ASTRO definition, respectively. The hazard rates for RT alone and RT plus ADT were proportional only for the nadir plus 2 ng/mL definition and seemingly unaffected by the length of follow-up. For RT with or without ADT, the nadir plus 2 ng/mL definition was the most specific (RT, 80% vs. RT plus ADT, 75%) with the greatest positive predictive value (RT, 36% vs. RT plus ADT, 25%) and overall accuracy (RT, 81% vs. RT plus ADT, 77%). A greater proportion of BF was diagnosed in the first 2 years of follow-up with the nadir plus 2 ng/mL definition compared with the ASTRO definition (13% vs. 5%, p = 0.0138, chi-square test).. The nadir plus 2 ng/mL definition was the best predictor of sustained, true, biochemical, and clinical failure, and was not affected by the use of ADT or follow-up length.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Combined Modality Therapy; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Predictive Value of Tests; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Conformal; Sensitivity and Specificity; Treatment Failure

Gonadotropin analogues are used in patients with prostate cancer for Leydig cell suppression with serum testosterone levels within the range after castration. Insufficient effect may have adverse consequences on the clinical course.. At the Norwegian Radium Hospital, serum testosterone is routinely analysed in patients who use gonadotropin analogues and are referred to the hospital for treatment of hormone-resistant prostate cancer.. Analyses of serum testosterone in two patients with advanced prostate cancer revealed insufficient androgen suppression in spite of continuous treatment with leuprorelin 11.25 mg. After substitution of leuprorelin by goserelin, serum testosterone decreased to levels compatible with those after surgical castration. In patients with advanced prostate cancer who use leuprorelin, monitoring of serum testosterone is necessary, with onset no later than 12 weeks after start of treatment. The diagnosis of "hormone resistant prostate cancer" requires that the patient's serum testosterone is measured within the range corresponding to surgical castration.

Topics: Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Outcome

Topics: Androgens; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Clinical Trials, Phase III as Topic; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Testosterone

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Clinical Trials as Topic; Goserelin; Humans; Male; Prostatic Neoplasms; Survival Analysis

Stage pT0 following prolonged neoadjuvant endocrine therapy (PPNET) of prostate cancer is of great clinical interest, because this finding suggests maximum tumor damage. Therefore pT0 patients are expected to have an extremely favorable PSA progression rate. The purpose of this study was to assess whether the PSA progression rate of pT0 patients after PPNET is lower than that of non-pT0 patients after PPNET.. 174 patients with previously untreated, clinical stage cT1-3 carcinomas were submitted to PSA monitored complete androgen deprivation therapy followed by radical prostatectomy (RP). In 138 patients the RP specimens showed residual cancer, in 36 patients no residual cancer was found. Biochemical progression was defined as PSA >/=0.2ng/ml. To control for confounding prognostic factors (Gleason score, cT-stage) between both groups a matched-pair analysis for the cumulative risk of biochemical failure was performed, resulting in 30 matched pairs.. With a median follow-up of 37.9 and 46.0 months in the matched non-pT0 and pT0 cohort respectively, matched-pair analysis failed to demonstrate significant differences in crude PSA relapse-free survival between both groups (p=0.7758).. The results suggest that patients converted into pT0 after PPNET do not represent a subgroup with an extremely favorable prognosis. However our results have to be confirmed by the assessment of larger cohorts of pT0 patients with a longer follow-up. The presented data do not allow drawing any conclusions on the prognostic impact of PPNET in general.

Topics: Anilides; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Flutamide; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Matched-Pair Analysis; Neoplasm Staging; Nitriles; Prognosis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Time Factors; Tosyl Compounds

The androgen-signaling pathway is critical to the development and progression of prostate cancer and androgen ablation is a mainstay of therapy for this disease. We performed a genome-wide expression analysis of human prostate cancer during androgen ablation therapy to identify genes regulated by androgen and genes differentially expressed after the development of resistance. Six hundred and fifty-four of 63,175 probe sets detected significant expression changes after 3 months of treatment with goserelin and flutamide. This included 149 genes that were also differentially expressed 36 hours after androgen withdrawal in LNCaP cells. These genes reflect the physiological changes that occur in treated tumors and include potential direct targets of the androgen receptor. Expression profiles of androgen ablation-resistant tumors demonstrated that many of the gene expression changes detected during therapy were no longer present suggesting a reactivation of the androgen response pathway in the absence of exogenous hormone. Therapy resistance was associated with differential expression of a unique set of genes that reflect potential mechanisms of reactivation. Specifically an up-regulation of the androgen receptor and key enzymes for steroid biosynthesis suggest that resistant tumors have increased sensitivity to and endogenous synthesis of androgenic hormones. The specific pathways of reactivation provide opportunities for classification of resistant tumors and targeted therapies.

Topics: Algorithms; Antineoplastic Agents, Hormonal; Cell Line, Tumor; Drug Resistance, Neoplasm; Drug Therapy, Combination; Flutamide; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Goserelin; Humans; In Situ Hybridization, Fluorescence; Male; Prostatic Neoplasms

Telomerase is a ribonucleoprotein complex that protects the ends of chromosomes from degradation. Its catalytic subunit, hTERT, controls its activity. Prior data in prostate carcinoma cases indicated that immunohistochemical hTERT reactivity increases with tumor grade and may be absent in lower grade cases. The effect of complete androgen ablation (CAA) on tumor hTERT expression was uncertain.. hTERT immunostaining was performed on the cancerous pretreatment biopsy tissue of 30 men who consecutively underwent CAA with bicalutamide and goserelin acetate for 30 days prior to undergoing radical prostatectomy, and on their tumor tissue from radical prostatectomy. As controls, biopsy and prostatectomy samples from 30 untreated men were studied. Nuclear staining was evaluated by two observers, and the change in staining between biopsy and prostatectomy samples was evaluated using the Student t test in both groups.. The percent of reactive tumor nuclei in treated men declined from 36.7% to 13.2% (P = 0.0001), and declined from 19.8% to 16.1% in untreated men (P = 0.4). The greater mean hTERT reactivity in the treated men's biopsy specimens was attributed to an increased proportion of higher (Gleason score > or = 7) grade tumors. The decline in hTERT immunostaining remained significant after normalizing it to that of the untreated group (P = 0.002). The original Gleason scores, corresponding declines in the percentage of reactive tumor nuclei, and significance were: Gleason score < or = 6: 11% (P = 0.03); Gleason score of 7: 23% (P < 0.006); and Gleason score > or = 8: 46% (P < 0.005) (from a mean 63% to 17%).. CAA for prostate carcinoma can be considered an antitelomerase therapy. The steepest reduction in telomerase activity was noted in the highest grade tumors.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Carcinoma; Catalytic Domain; Goserelin; Humans; Immunohistochemistry; Male; Middle Aged; Nitriles; Peptide Fragments; Prostatectomy; Prostatic Neoplasms; Telomerase; Tosyl Compounds

The aim of this study was to retrospectively compare the clinical outcomes achieved in 2 groups of patients with cT3 prostatic carcinoma undergoing neoadjuvant hormonotherapy and neoadjuvant hormonotherapy plus adjuvant hormonotherapy with external beam radiotherapy.. One hundred patients with cT3N0M0 prostatic carcinoma underwent radiotherapy to pelvic lymph nodes (45 Gy, 1.8 Gy/fraction) with a booster dose (65-70 Gy) to the prostatic cavity. Forty-four patients received neoadjuvant hormonotherapy (goserelin, starting 2 months before radiotherapy and continuing until the end of irradiation); 56 patients received neoadjuvant hormonotherapy plus adjuvant goserelin until disease progression, if present.. Patients undergoing adjuvant hormonotherapy as compared to those who received exclusive neoadjuvant therapy showed a higher reduction in PSA level below 1.0 ng/ml (p = 0.0211), a lower incidence of biochemical failures (p = 0.0170), a lower incidence of hematogenous metastases (p = 0.0320) and a trend suggestive of a better disease-free survival (p = 0.0660). At univariate analysis (logrank), Gleason score did not show a significant correlation with any of the end points analyzed. To the contrary, patients with tumor <15 mm showed a better local control (p = 0.0347) and biochemical failure-free survival (p = 0.0102). Furthermore, a trend between initial PSA level and incidence of hematogenous metastases was observed (p = 0.0519). Patients with a posttreatment PSA level <1.0 ng/ml had a lower incidence of metastases (p = 0.0237) and a better survival (p = 0.0178); patients with complete clinical response showed a lower incidence of biochemical failures (p = 0.0469). Radiotherapy doses >70 Gy showed a trend with biochemical failure-free survival (p = 0.0554). At multivariate analysis, a correlation between Gleason score and incidence of metastases (p = 0.0232), and between tumor diameter and local control (p = 0.0178) and biochemical failure-free survival (p = 0.0290) was recorded.. In patients with cT3N0M0 prostate carcinoma, prolonged hormonotherapy was shown to be significantly correlated with biochemical failure-free survival and distant metastasis-free survival. Furthermore, tumor size had a significant impact on biochemical failure-free survival as well as on local control.

Topics: Antineoplastic Agents, Hormonal; Carcinoma; Chemotherapy, Adjuvant; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Retrospective Studies

Topics: Aged; Androgen Antagonists; Drug Therapy, Combination; Fatal Outcome; Flutamide; Goserelin; Hepatic Encephalopathy; Humans; Male; Prostatic Neoplasms; Tumor Lysis Syndrome

We report a case of a seminal vesicle cyst supposed to be associated with prostate cancer in a 79-year-old Japanese man presenting with urinary retention. A fist-sized soft mass was palpated at the anterior wall of the rectum and serum prostate-specific antigen (PSA) was elevated to 59.8 ng/ml. Transrectal ultrasonography, computed tomography and magnetic resonance imaging revealed a retrovesical cystic mass measuring 7 cm in diameter and the absence of bilateral seminal vesicles. On vasography the lumen of the cystic lesion was visualized immediately, but the radiopaque fluid did not flow into the urethra. Transperineal prostate biopsy revealed moderately differentiated adenocarcinoma and puncture of the cyst revealed bloody fluid including sperm with a low PSA level. These findings strongly suggested that the mass was a seminal vesicle cyst caused by ejaculatory duct obstruction associated with prostate cancer. He has received endocrine therapy with goserelin acetate and bicalutamide for 6 months with no enlargement of the cystic lesion.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cysts; Diagnostic Imaging; Ejaculatory Ducts; Genital Diseases, Male; Goserelin; Humans; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Seminal Vesicles; Tosyl Compounds

To better understand bone metabolism and predict bone loss in treatment using gonadotropin-releasing hormone agonist for patients with prostate cancer.. The changes in bone mineral density and blood levels of bone metabolism markers and the level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen, a specific marker of bone resorption, and carboxy-terminal pro-peptide of human type I procollagen, a specific marker of bone formation, were examined in 27 consecutive patients with prostate cancer without bone metastasis.. After 2 years of gonadotropin-releasing hormone treatment, the bone mineral density was significantly lower (median 0.937 g/cm2) than before treatment. Pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen began to increase significantly 6 months after the start of treatment (3.0 to 8.3 ng/mL, median 4.6, at baseline versus 3.4 to 8.2 ng/mL, median 5.2, after 6 months). Carboxy-terminal pro-peptide of human type I procollagen began to show a significant rise 1 year after the start of treatment (from 72.8 to 221.5 ng/mL, median 102.0, at baseline to 82.7 to 293.4 ng/mL, median 132.0, at 1 year).. Functional coupling between bone resorption and formation was noted, and a decrease in bone mass, even in men, owing to androgen deficiency, was biochemically demonstrated. Fluctuations in these two bone metabolism markers preceded the decrease of bone mineral density. Therefore, these markers might be a predictor of bone loss.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Density; Bone Remodeling; Bone Resorption; Collagen Type I; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Peptide Fragments; Peptides; Procollagen; Prostatic Neoplasms; Testosterone

We determined the risk factors for osteoporosis and spinal fractures in men with prostate cancer receiving androgen deprivation therapy.. We performed a retrospective analysis of 87 consecutive men with prostate cancer receiving androgen deprivation therapy referred for evaluation of osteoporosis. Data were comprised of lateral thoracolumbar radiographs, bone densitometry, serum biochemistry and a detailed assessment of osteoporotic risk factors. Multivariate regression analysis was used to determine the major risk factors for osteoporosis and spinal fractures.. There were 38 (44%) men who were 74.5 years old with radiographic evidence of spinal fractures. They had an initial mean prostate specific antigen of 52.8 ng/ml and had received androgen deprivation therapy for a mean of 39.6 months (95% confidence interval 28.7 to 50.4). Mean spinal (quantitative computerized tomography t-score -4.2) and femoral neck bone mineral densities (dual energy x-ray absorptiometry t-score -2.1) were significantly lower than in men without spinal fractures (p < 0.001 for all measurements). In the regression analysis the duration of androgen deprivation therapy (p = 0.002), serum 25-hydroxyvitamin D levels (p = 0.003) and a history of alcohol excess (defined as more than 4 standard drinks daily, p = 0.04) were the main determinants of spinal fractures.. Prolonged androgen deprivation therapy, low serum 25-hydroxyvitamin D levels and a history of alcohol excess are important risk factors for osteoporosis and spinal fractures in men with prostate cancer.

Topics: Aged; Alcohol Drinking; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Comorbidity; Flutamide; Goserelin; Humans; Male; Multivariate Analysis; Nitriles; Osteoporosis; Prostatic Neoplasms; Retrospective Studies; Risk Factors; Spinal Fractures; Time Factors; Tosyl Compounds; Vitamin D

In living organism, excessive free radicals or oxidative damage which occur as a result of deficient antioxidant defensive mechanisms by the effect of endogenous and exogenous factors, influences especially developmental steps of chemically induced cancers. In our study, plasma malondialdehyde level (MDA) as an indicator of lipid peroxidation, erythrocyte glutathione (GSH) level as an indicator of antioxidant state, glutathione reductase (GSH-Red), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST) as an antioxidant enzymes and plasma vitamin E level were detected in patients with prostate cancer (21 males; age, 69.4 +/- 4.8 years) before and after three months of antiandrogenic therapy with goserelin acetate as luteinizing hormone releasing hormone (LHRH) analogue. Healthy people evaluated as a control group (20 males; age, 63.7 +/- 3.9). Erythrocyte GSH levels, the activities of GSH-Red and GSH-Px and plasma vitamin E levels were found significantly low in patients with prostate cancer when compared with the healthy subjects (p < 0.01, p < 0.05, p < or = 0.001 and p < or = 0.001 respectively). Plasma MDA level and erythrocyte GST activity of patient group were significantly higher than the levels of control group (p < or = 0.001 and p < or = 0.001 respectively). After antiandrogenic therapy erythrocyte GSH level, GSH-Red, GSH-Px activity and plasma vitamin E level were found unchanged. Significant decrease in plasma MDA level and significant increase in erythrocyte GST activity were detected in patient group (p < 0.05 and p < or = 0.01 respectively). The study has revealed the shift in the oxidant-antioxidant balance towards oxidative state in patients with metastatic prostate cancer. Our results showed that antiandrogenic therapy increased in GST activity, decreased in lipid peroxidation.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antioxidants; Erythrocytes; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Goserelin; Humans; Lipid Peroxidation; Male; Malondialdehyde; Middle Aged; Prostatic Neoplasms; Vitamin E

Our patient was a 61-year-old man with hormone-refractory prostate cancer and a rapidly rising serum prostate-specific antigen level. During the course of therapy for prostate cancer, abnormal blood counts and subsequent bone marrow biopsy led to a diagnosis of acute lymphoblastic leukemia. He was treated with a chemotherapeutic regimen in standard use for lymphoblastic leukemia, which resulted in an unusual response of his prostate cancer, with declining serum prostate-specific antigen levels that had reached undetectable levels at the time of the patient's death from acute sepsis and leukemic relapse. Autopsy showed minimal evidence of prostate cancer, localized to the prostate.

Topics: Adenocarcinoma; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cyclophosphamide; Cytarabine; Dexamethasone; Doxorubicin; Drug Resistance, Neoplasm; Fatal Outcome; Goserelin; Humans; Immunocompromised Host; Male; Methotrexate; Middle Aged; Neoplasm Proteins; Neoplasms, Second Primary; Neutropenia; Nitriles; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prostate-Specific Antigen; Prostatic Neoplasms; Recurrence; Sepsis; Tosyl Compounds; Vincristine

A 76-year-old man with prostate cancer T3N0M0 and increasing PSA was treated with goserelin three times in a half year. As soon as the first treatment, he described subjective muscle weakness. After the third treatment, he developed complex motoric symptoms and atypical central pain with a likely association to goserelin. His left arm had signs of spastic movement; pain deteriorated after relaxation. The right hand showed muscle cramps under passive movements of the left arm that were not typical for rigor. He felt aching and partial burning pain in his whole body. There were few allodynic areas, mainly in the left arm. Several treatment approaches failed and the patient died some weeks after the first contact with our pain clinic due to pneumonia.

Topics: Aged; Dyskinesia, Drug-Induced; Fatal Outcome; Goserelin; Humans; Male; Muscle Weakness; Pain; Prostatic Neoplasms

We assessed the impact of race on survival in men treated with external beam radiotherapy with or without hormonal therapy for localized prostate cancer in Radiation Therapy Oncology Group randomized trials.. Between 1975 and 1992, 2,048 men were treated for clinically localized prostate cancer in 1 of 4 consecutive prospective phase III randomized trials. After excluding nonblack and nonwhite men 2,012 remained for analysis. Patients were included in this analysis if they were deemed evaluable and eligible for the trial, and followup information and centrally reviewed pathological results were available. Short-term hormonal therapy consisted of goserelin acetate and flutamide administered 2 months before and during radiotherapy. Long-term hormonal therapy consisted of adjuvant goserelin acetate, which was generally given for 2 years or more. Pretreatment prostate specific antigen (PSA) findings were available in 430 cases (21%), including 213 treated with radiotherapy alone, 60 treated with short-term hormonal therapy and 157 on long-term hormonal therapy. Mean pretreatment PSA was 68.8 and 35.2 ng./ml. in black and white patients, respectively. Cox proportional hazards models were used to identify the impact of previously defined risk groups on overall and disease specific survival. Multivariate analysis was done for the significance of race using a stratified Cox model. Median followup in patients treated in early and late studies exceeded 11 and 6 years, respectively.. On univariate analysis black race was associated with lower overall and disease specific survival (p = 0.04, RR = 1.24 and p = 0.016, RR = 1.41, respectively). After adjusting for risk group and treatment type (with or without short-term or long-term hormonal therapy) race was no longer associated with outcome (p >0.05). The trend for a persistent difference in survival was likely due to the higher tumor burden in black men, as reflected in higher PSA.. As previously reported, tumor grade (Gleason score), palpation T stage, lymph node status, pretreatment PSA and treatment type are major predictors of overall and disease specific survival. We noted no evidence that race has independent prognostic significance in patients treated for prostate cancer in Radiation Therapy Oncology Group prospective randomized trials.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Black or African American; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Flutamide; Goserelin; Humans; Male; Multivariate Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Risk Factors; Survival Rate; White People

A 66-year-old male patient with advanced prostate cancer presented with bony metastases, including pathologic fractures and hepatosplenomegaly. The patient responded to luteinizing hormone-releasing hormone agonists for more than 1 year. A clear progression while taking luteinizing hormone-releasing hormone agonists manifested as a progressive rise in prostate-specific antigen, alkaline phosphatase, hepatosplenomegaly, and myelophthisic pancytopenia. We administered capecitabine for 5 months with a complete clinical response. At last follow-up, the patient's liver function tests and prostate-specific antigen level have normalized. Liver size by computed tomography and blood counts both improved. To our knowledge, no previous case reports of capecitabine in the treatment of prostate cancer have been published.

Topics: Adenocarcinoma; Aged; Alkaline Phosphatase; Antimetabolites, Antineoplastic; Antineoplastic Agents, Hormonal; Capecitabine; Deoxycytidine; Fluorouracil; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Treatment Failure; 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

Androgen deprivation as a treatment for prostate cancer has evolved since the pioneering studies of Huggins and Hodges 60 years ago using surgical castration or estrogen treatments. The most common hormonal treatments today use injections of luteinizing hormone-releasing hormone (LHRH) agonists. The US Food and Drug Administration (FDA) has approved 5 LHRH agonist formulations for treatment of prostate cancer in the United States. Of these approved products, 3 involve different delivery systems for the LHRH superagonist leuprolide acetate. Sustained-release formulations of 2 distinct LHRH agonists, goserelin acetate and triptorelin pamoate, are also commercially available. This review focuses on new data on a novel formulation of leuprolide acetate (Eligard; Atrix Laboratories Inc., Fort Collins, CO) that incorporates a unique mixture of selected polymers and solvents to achieve sustained drug delivery after subcutaneous injection. The FDA has approved 1-month and 3-month formulations of Eligard, and 4-month and 6-month products are in development. In clinical trials, Eligard achieves reliable and sustained suppression of serum testosterone to castration levels (< or =50 ng/dL). Of the patients treated with the 1-month and 3-month formulations, 98% (115 of 117) and 94% (104 of 111), respectively, reached testosterone levels of < or =20 ng/dL. Breakthroughs, defined as testosterone levels >50 ng/dL after achievement of castration levels, occurred rarely at 0% (0 of 117) for the 1-month and at 0.9% (1 of 111) for the 3-month formulations in patients receiving Eligard. The degree of disease control and the adverse-events profile are commensurate with the effectiveness of the testosterone suppression; the incidence of severe hot flashes is actually lower than anticipated. Additional studies with these novel formulations are warranted.

Topics: Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Drug Approval; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Triptorelin Pamoate; United States; United States Food and Drug Administration

The purpose of this investigation was to explore the potential benefit of hormone therapy in addition to external beam radiotherapy for patients with early-stage (T1-2), intermediate-(prostate-specific antigen [PSA] > 10 or Gleason score >or= 7) or high-risk (PSA > 10 and Gleason score >or= 7) prostate cancer. The charts of 412 patients with early-stage intermediate- and high-risk prostate cancer treated with external beam radiotherapy with or without a 4-month total androgen blockade were reviewed. The groups were balanced with respect to age, pretreatment PSA, and stage, but differed with respect to Gleason score and radiation dose. Biochemical failure rates, as defined by the ASTRO consensus panel, were compared between those receiving and those not receiving hormones. With a median follow-up of 2.0 years, the biochemical failure rate was 12.1 versus 23.1% (p = 0.02) in favor of those receiving hormones. This difference was seen for the subgroups followed for more than 6 months (12.5 vs. 25.0%), more than 9 months (14.5 vs. 26.3%), and more than 12 months (17.3 vs. 27.0%). Thus, biochemical failure decreased with the administration of hormone therapy in this group of patients with early stage, intermediate- or high-risk prostate cancer. This finding requires validation by ongoing randomized trials.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Flutamide; Goserelin; Humans; Male; Neoadjuvant Therapy; Nitriles; Prostatic Neoplasms; Survival Analysis; Tosyl Compounds

In preparation of an intercontinental Phase III trial comparing continuous maximal androgen blockade (MAB) to intermittent androgen suppression (IAS) in untreated metastatic prostate cancer, a feasibility study on IAS was accomplished.. 107 patients (median follow-up 92 weeks) were treated with MAB until a PSA nadir was reached. Nadir was defined as PSA below 20 ng/ml corresponding to PSA reduction by at least 80% of baseline value. Criteria for restarting treatment was PSA >20 ng/ml and PSA > nadir + 50%. Trials aim was to assess the likelihood that 80% of patients would reach a first nadir and that 80% of these would also reach a second nadir.. 51.4% of patients had some degree of pain at entry, 27.1% had >15 hot spots, 23.7% demonstrated obstruction. Only 17.8% had normal potency, 56.1% were totally impotent. One to seven cycles of treatment were given. 76.6% of patients reached a 1st nadir after a median of 19 weeks of treatment, 84.1% of these started the 2nd cycle and 71% of them reached a 2nd nadir after a median of 13.6 weeks. Median time off-treatment was 14.3 and 16.0 weeks corresponding to 38.4% and 48.5% of the duration of each cycle. A similar proportion of patients was reported to be potent during follow-up compared to baseline. 32.7% of patients died during follow-up, 82.9% of prostate cancer.. Around 75% of the patients achieved a nadir at each cycle. The concept of IAS seems to be feasible and warrants further investigation.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Feasibility Studies; Goserelin; Humans; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

Topics: Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Docetaxel; Epothilones; Goserelin; Humans; Male; Medical Oncology; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Taxoids

The Genito-Urinary Radiation Oncologists of Canada (GUROC) have produced a consensus statement on radiotherapy in prostate cancer. This paper summarizes the consensus statement with regard to risk grouping and the role of hormones and radiotherapy. Survival is the most important outcome in the assessment of patients treated with radiotherapy. Other outcomes of interest include disease-free survival, metastatic-free survival, local control, biochemical measures, toxicity, efficacy, and quality of life. Risk groupings based on prognostic data are increasingly used in the management of prostate cancer. These groupings have been correlated to prognosis in several studies, and are helpful in identifying optimum treatments, and as a research tool to evaluate new treatments and modalities. Adjuvant hormone treatment with radiotherapy has been demonstrated in two studies (Bolla and RTOG 85-31) to be beneficial in patients with locally advanced prostate cancer. Neoadjuvant hormone treatment in patients with low- and intermediate-risk disease is being evaluated in a RTOG study and its utility in these patients will be clarified when the study results are available. The GUROC consensus statement recommends that patients with high-risk non-metastatic prostate cancer be treated with adjuvant hormone therapy for 2-3 years. Part of this hormone treatment may be administered in a neoadjuvant fashion. Adjuvant hormone treatment should not be routinely used in low- and intermediate-risk prostate cancer. Neoadjuvant hormone treatment is recommended prior to radiotherapy in patients with bulky tumors. The results of ongoing research will further clarify the use of hormone treatment with radiotherapy.

Topics: Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Humans; Male; Prostatic Neoplasms; Risk Assessment

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Diagnosis, Differential; Goserelin; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatectomy; Prostatic Neoplasms; Testis; Testosterone

We report 3 patients referred to the bone clinic after spinal fractures. Dual energy X-ray absorptiometry showed severe osteoporosis. Each patient was found to have a history of prostatic carcinoma and long-term treatment with goserelin. We suggest that all patients who have received androgen deprivation therapy for more than 1 year should be evaluated by bone densitometry.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Carcinoma; Densitometry; Femoral Fractures; Follow-Up Studies; Fractures, Spontaneous; Goserelin; Humans; Male; Osteoporosis; Prostatic Neoplasms; Risk Assessment; Severity of Illness Index; Spinal Fractures; Thoracic Vertebrae

Topics: Androgen Antagonists; Combined Modality Therapy; Controlled Clinical Trials as Topic; Cyproterone Acetate; Goserelin; Humans; Male; Prostatic Neoplasms; United States

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Luteinizing Hormone; Male; Prostatic Neoplasms; Radiotherapy, Conformal; Reference Values; Testosterone

Several investigators have examined the role of hormonal therapy before definitive local therapy for locally advanced prostate cancer to improve outcome. We evaluated the resectability rate and clinical response rate to 16 weeks of total androgen blockage therapy for clinically locally prostate cancer before radical prostatectomy, and progression-free survival in this multi-institutional study.. Southwest Oncology Group 9109 was a phase II feasibility study designed to treat patients with clinical stage C prostate cancer (T3, T4, N0 and M0). Cases were classified by stage T3 versus T4 and bulky (greater than 4 cm.) versus nonbulky (or less 4 cm.) disease. The neoadjuvant agents used were goserelin and flutamide before radical prostatectomy.. A total of 62 patients were accrued to the study and 1 patient was ineligible. There were 2 protocol deviations and these patients refused to undergo prostatectomy after hormonal therapy. Four patients went off protocol treatment because they were not considered surgical candidates. The racial distribution was 72% white, 20% black, 7% Hispanic and 2% Asian. Clinical stage at diagnosis was T3 in 97% and T4 in 3% of cases. Of the patients 39% were diagnosed with bulky disease. Of the 61 eligible patients 55 (90%) underwent a prostatectomy. The 5-year progression-free survival estimate was 70% (24 of 61 cases failed) and the 5-year survival estimate was 90% (11 of 61 deaths). Most of the patients in this trial would have been considered inoperable and referred to radiation oncology.. Neoadjuvant hormonal therapy followed by radical prostatectomy is reasonable and appropriate for clinical stage T3 prostate cancer. A progression-free and overall 5-year survival of 70% and 90%, respectively, compares favorably to Radiation Therapy Oncology Group neoadjuvant trial outcomes for this stage of prostate cancer.

Topics: Aged; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Feasibility Studies; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms; Survival Rate

To present the biochemical cure rates (biochemically no evidence of disease) after external irradiation (RT) in patients with high-risk prostate cancer after radical prostatectomy.. Seventy-six patients who underwent radical prostatectomy and subsequent RT were included in this analysis. No patient received hormonal therapy. Adjuvant RT was administered in 35 patients (46%), and 41 patients (54%) underwent salvage RT. After prostatectomy, the Gleason score was <7 in 87%, and 24% had seminal vesicle invasion. The median RT dose in the adjuvant RT and salvage RT groups was 60 Gy and 65 Gy, respectively. The biochemical cure rate was defined as a serum prostate-specific antigen of < or =0.2 ng/mL.. The overall 5-year Kaplan-Meier biochemical control rate from the end of RT was 70%. The 5-year biochemical cure rate for adjuvant RT was significantly superior to that after salvage RT (86% vs. 57%). The significant predictors of biochemical failure were seminal vesicle invasion in the adjuvant RT group and the presence of Gleason grade 4 or 5 in the salvage RT group. The clinical local control rate in the prostate bed was 100%.. This report demonstrates the efficacy of RT in achieving high biochemical cure rates after radical prostatectomy. Additional clinical studies are required to determine the optimal treatment of patients at high risk of biochemical failure after postprostatectomy RT.

Topics: Aged; Combined Modality Therapy; Disease-Free Survival; Goserelin; Humans; Male; Middle Aged; Neoplasm Invasiveness; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Adjuvant; Retrospective Studies; Salvage Therapy; Seminal Vesicles

The objective of this work was to determine the effect of androgen deprivation therapy (ADT) on rates of bone mineral density (BMD) loss in men with prostate cancer. It was a prospective study comparing men receiving ADT to age matched controls for 2 y. Subjects received a history, physical exam, bone mineral density measurement, and laboratory evaluation every 6 months. Thirty-nine subjects receiving continuous ADT for prostate cancer (subjects) were compared to 39 age-matched controls not receiving ADT (controls). Twenty-three subjects and 30 controls completed the study through 24 months. Men in the ADT group demonstrated greater rates of bone mineral density loss than men in the control group at every site except the lumbar spine. Twenty-four month per cent of bone mineral density loss is presented as mean+/-standard error (s.e.). At the distal forearm, the ADT group value was -9.4%+/-1.0% and -4.4%+/-0.3% for controls (P<0.0005). The ADT group femoral neck values were -1.9%+/-0.7% and 0.6%+/-0.5% in the control group (P=0.0016). The ADT group total hip value was -1.5%+/-1.0% and 0.8%+/-0.5% in the control group (P=0.0018). The ADT group trochanter value was -2.0%+/-1.3% and -0.1%+/-0.5% in the control group (P=0.0019). The ADT group lumbar spine value was -0.2%+/-0.8 % and 1.1%+/-0.6% in the control group (P=0.079). Our data demonstrate greater rates of bone mineral density loss in men receiving androgen deprivation therapy for prostate cancer.

Topics: Absorptiometry, Photon; Adenocarcinoma; Aged; Amino Acids; Androgen Antagonists; Androgens; Anilides; Antineoplastic Agents, Hormonal; Biomarkers; Bone Density; Bone Remodeling; Calcium; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Neoplasms, Hormone-Dependent; Nitriles; Orchiectomy; Osteoporosis; Prospective Studies; Prostatic Neoplasms; Testosterone; Tosyl Compounds

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Fatigue; Gonadotropin-Releasing Hormone; Goserelin; Hot Flashes; Humans; Male; Multicenter Studies as Topic; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Quality of Life; Radiotherapy, Conformal; Randomized Controlled Trials as Topic; Sexual Dysfunction, Physiological; Survival Rate; Testosterone; Treatment Outcome

To study the impact of hormonal therapy (HTx) on intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation.. Patients with Stage T1b-T3bN0 prostate cancer, and Gleason score > or = 7 or prostate-specific antigen (PSA) level >10 ng/mL were treated with seed implantation with or without HTx. Their disease was defined as intermediate risk (PSA 10-20, Gleason score 7, or Stage T2b) or high risk (two or more intermediate criteria, or PSA >20 ng/mL, Gleason score 8-10, or Stage T2c-T3). The median follow-up for 201 eligible patients was 42 months (range 18-110). Biochemical failure was defined as a rising PSA >1.0 ng/mL. Pretreatment disease characteristics, implant dose, and HTx were evaluated using univariate and multivariate analyses.. HTx significantly improved 5-year actuarial freedom from biochemical failure rate, 79% vs. 54% without HTx. In addition, high-dose, PSA < or = 15 ng/mL, intermediate risk, and Stage T2a or lower significantly improved outcome in the univariate analyses. HTx was the most significant predictor of 5-year actuarial freedom from biochemical failure (p <0.0001) in a multivariate analysis. The best outcome was in the intermediate-risk patients treated with a high implant dose and HTx, resulting in a 4-year actuarial freedom from biochemical failure rate of 94%.. In this retrospective review, HTx improved outcome in intermediate- to high-risk prostate cancer patients treated with brachytherapy. HTx was the most important prognostic factor in the univariate and multivariate analyses.

Topics: Adult; Aged; Analysis of Variance; Androgen Antagonists; Brachytherapy; Combined Modality Therapy; Follow-Up Studies; Goserelin; Humans; Iodine Radioisotopes; Leuprolide; Male; Middle Aged; Neoplasm Staging; Palladium; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radioisotopes; Radiopharmaceuticals; Retrospective Studies; Risk; Treatment Failure

Advanced prostate cancer is treated initially by central suppression of androgen production by luteinizing hormone-releasing hormone (LHRH) agonists. Intriguingly, even hormone-independent cancers often show some, if only slight, growth retardation when these agonists are delivered in pharmacological doses. Previous studies have shown in cell lines and animal xenograft models that activation of peripheral LHRH receptors on prostate carcinoma cells lead to growth suppression. In parallel, there is a decrease of epidermal growth factor receptors (EGFRs) and activity. Because autocrine EGFR stimulation exists in most, if not all, prostate carcinomas and is required for cell proliferation, we asked whether LHRH signaling cross-attenuated EGFR to limit tumor growth. One possible mechanism was suggested by LHRH receptors triggering phospholipase-C (PLC) to activate protein kinase C (PKC) because PKC activation limits EGFR tyrosine kinase activity by phosphorylating EGFR at threonine 654.. To determine the role of this cross-attenuation mechanism, we mutated the threonine 654 amino acid to an alanine (A654) to abrogate this inhibition. DU-145 cells stably expressing wild-type and A654 EGFR were grown as xenografts in the s.c. space of athymic mice.. DU-145 cells, overexpressing wild-type EGFR, formed tumors in athymic mice that were inhibitable by goserelin acetate (Zoladex). Tumors expressing the A654 EGFR were resistant to this growth inhibition. These results paralleled in vitro studies in which goserelin acetate blocked proliferation of the WT DU-145 but not A654 DU-145 cells.. These data support the model of LHRH agonists preventing EGFR-mediated tumor growth through a PKC pathway. This suggests new targets of modulatory intervention to limit the growth of androgen-independent prostate carcinomas.

Topics: Animals; Antineoplastic Agents, Hormonal; Cell Division; Dose-Response Relationship, Drug; Enzyme Activation; ErbB Receptors; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Prostatic Neoplasms; Protein Kinase C; Signal Transduction; Tetradecanoylphorbol Acetate; Time Factors; Tumor Cells, Cultured

We assessed the degree of prostate downsizing using androgen deprivation, and determined its relation to clinical and pathological variables.. From June 1994 to January 2000, 107 patients with prostate cancer received androgen deprivation before interstitial brachytherapy at our hospital. All charts were reviewed for clinical, pathological and treatment related variables. Prostate volume was measured using transrectal ultrasound. All variables were analyzed with regard to the degree of prostate downsizing.. Mean percent volume reduction of the prostate was 33% after a 3.7-month average duration of androgen deprivation. Larger prostate volume before androgen deprivation and longer deprivation duration statistically correlated with mean percent volume reduction. Simple linear and multiple regression analyses revealed that these 2 variables remained significant predictors of percent volume reduction. Subgroup analysis indicated that a significant difference was seen in patients who received androgen deprivation with luteinizing hormone releasing hormone agonists alone versus those who received treatment with total androgen blockade (luteinizing hormone releasing hormone agonists plus antiandrogens 30% versus 35%, p = 0.04), and when prostate volume before androgen deprivation was less than 50 cc versus larger volumes (30% versus 35%, p = 0.01). Of patients with an initial prostate volume of greater than 50 cc 82% achieved a volume of less than 50 cc after androgen deprivation therapy.. Androgen deprivation therapy before brachytherapy is a method of downsizing the prostate to overcome anatomical limitations, including larger gland volume and pubic arch interference.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Brachytherapy; Combined Modality Therapy; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostate; Prostatic Neoplasms; Regression Analysis; Ultrasonography

Topics: Antineoplastic Agents, Hormonal; Bias; Cause of Death; Chemotherapy, Adjuvant; Female; Goserelin; Humans; Male; Mass Screening; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Survival Rate

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Disease Progression; Drug Resistance, Neoplasm; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms

The aim of this study was to investigate the prognostic value of prostate-specific antigen (PSA) dynamics in patients treated with combined androgen blockade (CAB).. Patients with locally advanced or metastatic prostate cancer (n = 317) received bicalutamide (50 mg once daily) plus either goserelin acetate or surgical castration for 48 weeks. Cox's proportional hazard analysis was used to determine whether the decline of PSA following the use of this combination is predictive of a delay in progression.. PSA levels at weeks 4 and 12 were statistically significant prognostic markers in predicting disease progression. The PSA rate of change to week 12 was also a statistically significant prognostic marker, although the PSA rate of change at week 4 did not reach statistical significance. These results were statistically less robust than those for PSA levels. Bicalutamide plus castration was well tolerated and effective in advanced prostate cancer.. These results suggest that PSA dynamics at weeks 4 and 12 may predict time to progression in advanced prostate cancer treated with CAB.

Topics: Aged; Aged, 80 and over; Anilides; Antineoplastic Agents; Combined Modality Therapy; Disease Progression; Goserelin; Humans; Male; Middle Aged; Nitriles; Orchiectomy; Predictive Value of Tests; Prostate-Specific Antigen; Prostatic Neoplasms; Risk Factors; Time Factors; Tosyl Compounds

Conformal therapy of prostate cancer is based on high-dose irradiation to the entire prostate gland. The aim of this study was to analyze the pattern of intraprostatic recurrence in patients undergoing external beam radiotherapy (EBRT) at a dose of 65-70 Gy to evaluate whether conventional radiotherapy doses are adequate to control microscopic disease outside the primary tumor and therefore whether high-dose irradiation can be exclusively focused on the macroscopic disease.. The clinical and radiologic reports of 118 patients with prostate cancer undergoing EBRT (64.8-70.2 Gy) combined with hormonal therapy were evaluated. In all patients, before and after therapy, the size and site of the primary neoplasm within the prostate were assessed by clinical examination and imaging studies.. With a median follow-up of 45 months (range 14-119), the 5-year actuarial local control rate was 83.9%. Twelve patients had an intraprostatic recurrence, with the appearance of a new nodule (in 5 patients with a complete response after therapy) or increased nodular size compared with the minimal size (in the 7 other patients). In all patients, on the basis of a semiquantitative evaluation of the site of recurrence, this was shown to originate within the initial tumor volume.. The results of this analysis seem to confirm some histologic findings observed in patients undergoing prostatectomy for local recurrence after radiotherapy that suggest that local recurrence usually originates in the primary tumor rather than in focal prostatic intraepithelial neoplasia. This observation might justify the application of conformal therapy procedures aimed at identifying the gross tumor volume, in the phase of boost, exclusively with the primary tumor.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Conformal; Retrospective Studies; Treatment Failure

In the present study, we investigated the diagnostic effectiveness of biochemical markers of bone turnover for the detection of bone metastasis from prostate cancer and changes in the levels of these markers caused by hormonal therapy. Ninety-five patients with prostate cancer were divided into one of three groups: 26 patients with bone metastasis (BM(+)), 35 patients without bone metastasis on nonhormonal therapy (BM(-)HT(-)) and 34 patients without bone metastasis on hormonal therapy (BM(-)HT(+)). All patients in the BM(+) group had received hormonal therapy. Serum or urinary levels of the following biochemical markers of bone turnover were examined: bone-specific alkaline phosphatase (B-ALP), osteocalcin (OC), type I procoIlagen C-propeptide (PICP), type I collagen cross-linked C-telopeptide (ICTP), C-telopeptide fragment (CTx), N-telopeptide fragment (NTx), total pyridinoline (T-Pyr), total deoxypyridinoline (T-D-Pyr) and free deoxypyridinoline (F-D-Pyr). The BM(+) group showed significantly higher values than the BM(-)HT(-) group for B-ALP, PICP, NTx, CTx, T-Pyr, T-D-Pyr, and F-D-Pyr. Compared with the BM(-)HT(+) group, the BM(-) group showed significantly higher values for B-ALP, ICTP, NTx, T-Pyr and T-D-Pyr. The levels of B-ALP, NTx, CTx, T-D-Pyr and F-D-Pyr were significantly different between the BM(-)HT(-) and BM(-)HT(+) groups. All markers, except OC and CTx, significantly were correlated with the extent of bone metastasis on bone scintigraphy. Of all markers, receiver operating characteristic (ROC) analyses revealed B-ALP and F-D-Pyr to be the most sensitive and specific for differentiation between the BM(+) and BM(-)HT(-) groups with regard to bone formation and resorption. respectively. In contrast, B-ALP and ICTP were most sensitive and specific for differentiation between the BM(+) and BM(-)HT(+) groups. The results suggest that hormonal therapy greatly affects the efficacy of PICP, CTx and F-D-Pyr in the diagnosis of bone metastasis, whereas its effects on ICTP are small. Although bone metabolic markers would be useful in the diagnosis of bone metastasis from prostate cancer, the effects of hormonal therapy on bone metabolism should be kept in mind in their evaluation.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Flutamide; Goserelin; Humans; Male; Osteogenesis; Prostatic Neoplasms; Radionuclide Imaging; ROC Curve

To assess magnetic resonance (MR) measures of vascular permeability of prostate cancer treated with androgen deprivation and to correlate these with morphologic appearances and serum prostate-specific antigen (PSA) levels.. MR examinations in 56 consecutive patients with prostate cancer were performed before and after luteinizing hormone-releasing hormone analog treatment. T2-weighted and contrast medium-enhanced T1-weighted MR images were obtained. Pre- and posttreatment comparisons of morphologic features, glandular volume, and enhancement-related parameters (capillary permeability, leakage space, gadolinium accumulation) were made.. Fifty-five tumors were seen before treatment; 42, after treatment. Signal intensity in the peripheral zone and seminal vesicles decreased on T2-weighted images in 42 (75%) and 25 (45%) patients, respectively. Median volume in tumor decreased by 65% (95% CI: 55%, 76%); in central gland, by 30% (95% CI: 25%, 35%). Reductions in tumor permeability (P <.001) and changes in washout patterns were observed (P <.001). Tumor permeability reductions coincided with a decrease in serum PSA levels in 91% of patients. A weak correlation between tumor permeability and volume change was seen (r = 0.55, P =.04). Reductions in peripheral zone (P <.001) and central gland (P =.009) permeability were noted.. Androgen deprivation decreases tumor volume and vascular permeability and impairs detection of prostate cancers. Use of MR estimates of permeability may be an additional way of assessing prostatic tumor response to antiandrogen treatment.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Capillary Permeability; Cyproterone Acetate; Drug Therapy, Combination; Goserelin; Humans; Magnetic Resonance Imaging; Male; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Cachexia is rarely observed in patients with advanced prostate cancer treated with combined androgen blockade. Androgens play an important role in the regulation of body mass composition and influence the secretion of leptin, the appetite regulating hormone. The aim of the study was to assess the influence of a combined treatment with nonsteroidal antiandrogen and LH-RH analogue on the hormonal regulation of appetite and changes in body mass in patients with advanced prostate cancer (Whitmore-Jewett stage D1 or D2). Eighteen patients with prostate cancer and 17 healthy subjects matched for age and body mass index were included. In all patients serum concentrations of leptin, neuropeptide Y (NPY), insulin, testosterone and estradiol were measured before and after four and twelve weeks of androgen blockade. Pretreatment serum leptin levels were similar in patients with prostate cancer and in the controls. In a multiple regression analysis only body mass index and testosterone significantly contributed to the variation of plasma leptin. During the treatment body mass and plasma leptin significantly increased while NPY decreased. The change of plasma NPY was significant only after 4 weeks of therapy. This study shows that the afferent regulation of leptin secretion is unchanged in advanced prostate cancer. Androgen ablation significantly increases body mass and influences secretion of appetite regulating hormones. Testosterone appears to play a significant role in the regulation of leptin secretion.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Appetite; Body Constitution; Body Mass Index; Body Weight; Estradiol; Flutamide; Goserelin; Humans; Insulin; Leptin; Male; Middle Aged; Neuropeptide Y; Prostatic Neoplasms; Regression Analysis; Testosterone

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Goserelin; Humans; Male; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms

Topics: Antineoplastic Agents, Hormonal; Clinical Trials as Topic; Combined Modality Therapy; Goserelin; Humans; Male; Neoplasm Staging; Population Surveillance; Prostatic Neoplasms

Various reports suggest a role for endothelin-1 in prostatic carcinoma. The objective of the current study was to evaluate the changes of the immunodetectable endothelin-1 in prostatic carcinomas characterized by different grades of regression due to total androgen withdrawal.. An immunohistochemical study was made on eleven prostatic carcinomas treated with neoadjuvant hormonal therapy for 3 months, followed by radical prostatectomy. Another ten specimens of untreated carcinomas were studied for comparison. An appraisal of androgen receptors was associated. A highly specific polyclonal antibody against endothelin-1 and a commercial monoclonal mouse antibody for androgenic receptors were used.. In all cases, a prevalent quantity of androgenic receptor-positive tumor cells were present. Neoplastic cells of untreated carcinomas showed a strong and heterogeneous staining for endothelin -1. In unregressed areas of treated cases, the features of endothelin-1 and androgen-receptor staining were the same as those of untreated cases. In areas characterized by moderate histologic regression, the endothelin-1 staining became more heterogeneous. In areas of strong histologic regression, a diffuse membrane staining was often noted. Only in completely regressed cancer cells was a definite loss of immunodetectable endothelin-1 and androgenic receptors observed.. Endothelin-1 is one of the proteins intrinsic to prostatic epithelial cells, both benign and malignant. In cases treated with androgen withdrawal, histologic regression is not uniform. In unmodified areas, immunodetectable endothelin-1 and androgenic receptors also are unmodified, thus suggesting some mechanism that substitutes for the action of androgen. Only neoplastic cells with complete histologic regression also lose androgenic receptors and endothelin-1, whereas the preserved immunostaining in deeply modified prostatic neoplastic cells seems to indicate that these cells still are potentially active.

Topics: Aged; Antineoplastic Agents, Hormonal; Cyproterone Acetate; Endothelin-1; Goserelin; Humans; Immunoenzyme Techniques; Leuprolide; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms; Receptors, Androgen; Treatment Outcome

The meta-analysis of maximal androgen blockade (MAB) concluded that there is no survival advantage of MAB over castration alone. However, the results from the largest trials yield conflicting results.. The design and results of three trials were examined.. Most studies were planned to detect an over-optimistic difference in survival and immature data were published. The survival curves show that statistical assumptions are not fulfilled. Excluding from the meta-analysis all trials where a negative impact of disease flare on survival could not be excluded resulted in no difference in survival between MAB and castration.. Trials of MAB should be planned to detect differences of no more than 5-10% in median survival. The analyses should only be carried out on mature data and should take into account the possibility of a negative impact on survival due to disease flare if no anti-androgen has been given initially with an LH-RH agonist.

Topics: Androgen Antagonists; Anilides; Clinical Trials, Phase III as Topic; Cyproterone Acetate; Factor Analysis, Statistical; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Imidazoles; Imidazolidines; Leuprolide; Male; Meta-Analysis as Topic; Nitriles; Orchiectomy; Prognosis; Prostatic Neoplasms; Research Design; Survival Analysis; Tosyl Compounds; Treatment Outcome

The majority of men who undergo surgical or medical castration due to prostatic carcinoma develop vasomotor symptoms with hot flushes. The mechanisms behind these symptoms are poorly understood. One possible explanation is a release of the vasodilatory peptide calcitonin gene-related peptide (CGRP) from perivascular nerves, which seem to be involved in the mechanisms behind vasomotion and sweating in postmenopausal women. The aim of this report was to investigate whether CGRP is involved in vasomotion in men after castration therapy.. Twenty-four hour urine excretion of CGRP was analysed in 15 men with prostatic carcinoma, using radioimmunoassay before and 3 months after surgical or medical castration.. Eleven of the 15 men developed hot flushes during the observation period of 3 months. Twenty-four hour urine excretion of CGRP did not change significantly after castration, either in the group as a whole or in those 11 men who developed hot flushes.. Even though we did not observe any significant changes in 24-h urine excretion of the potent vasodilator CGRP after castration it is possible that serum levels of CGRP increase during hot flushes, without having an effect on the 24-h urine excretion of the peptide.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Calcitonin Gene-Related Peptide; Goserelin; Hot Flashes; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms

In the clinical study of prostate cancer, the effect of androgen ablation on glucose metabolism in cancer tissue has not been elucidated. The purpose of this study was to investigate the change in glucose utilization due to endocrine therapy for prostate adenocarcinoma. Ten patients with histologically proven prostate cancer were prospectively investigated with (18)F-fluorodeoxyglucose and positron emission tomography (FDG PET) prior to and after the initiation of endocrine therapy. FDG uptake was calculated to measure glucose utilization in cancer tissue. The change in FDG accumulation was compared with changes in serum prostate specific antigen (PSA) level and prostate size. FDG accumulation in the prostate decreased in all patients 1-5 months after the initiation of hormone therapy. The serum PSA level and prostate size measured on computerized tomography (CT) also decreased in these periods. A decrease in FDG accumulation was also demonstrated in metastatic sites. In this study, there appeared to be a decrease in FDG uptake in prostate cancer after endocrine therapy not only in primary prostate cancer lesions but also at metastatic sites, suggesting that the glucose utilization by tumours was suppressed by androgen ablation.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Fluorodeoxyglucose F18; Glucose; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Tomography, Emission-Computed

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Pituitary Apoplexy; Prostatic Neoplasms

To compare health-related quality-of-life outcomes after primary androgen deprivation (AD) therapy with orchiectomy versus luteinizing hormone-releasing hormone (LHRH) agonists for patients with prostate cancer.. Men (n = 431) newly diagnosed with all stages of prostate cancer from six geographic regions who participated in the Prostate Cancer Outcomes Study and who received primary AD therapy but no other treatments within 12 months of initial diagnosis were included in a study of health outcomes. Comparisons were statistically adjusted for patient sociodemographic and clinical characteristics, timing of therapy, and use of combined androgen blockade.. More than half of the patients receiving primary AD therapy had been initially diagnosed with clinically localized prostate cancer. Among these patients, almost two thirds were at high risk of progression on the basis of prognostic factors. Sexual function outcomes were similar by treatment group both before and after implementation of AD therapy. LHRH patients reported more breast swelling than did orchiectomy patients (24.9% v 9.7%, P <.01). LHRH patients reported more physical discomfort and worry because of cancer or its treatment than did orchiectomy patients. LHRH patients assessed their overall health as fair or poor more frequently than did orchiectomy patients (35.4% v 28.1%, P =.01) and also were less likely to consider themselves free of prostate cancer after treatment.. Most endocrine-related health outcomes are similar after surgical versus medical primary hormonal therapy. Stage at diagnosis had little effect on outcomes. These results provide representative information comparing surgical and medical AD therapy that may be used by physicians and patients to inform treatment decisions.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cross-Sectional Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Orchiectomy; Patient Satisfaction; Prostatic Neoplasms; Quality of Life; Regression Analysis; Sexuality

This study was carried out to evaluate the possible long-term endocrine effect of short-term neoadjuvant leuteinizing hormone-releasing hormone analogue (LHRHa) administration in localized prostate cancer. A total of 419 men were treated for 3-6 months at The Royal Marsden NHS Trust by neoadjuvant androgen suppression using monthly depot injections of LHRHa before radical radiotherapy. Serum testosterone (852 measurements), leuteinizing hormone (LH) (799 measurements), and follicle-stimulating hormone (FSH) levels (801 measurements) were grouped according to their timing in relation to hormonal treatment and then analysed. Suppression of pituitary gonadotrophins and testosterone after the administration of LHRHa and their recovery after cessation of the drug was clearly observed. Median serum testosterone levels decreased from 16 nmol/l to 14 nmol/l when comparing prehormonal and follow-up phases. The same comparison showed an increase in median serum LH and FSH levels, with the median LH rising from 5 u/l to 8 u/l and the median serum FSH rising from 6 u/l to 20 u/l. On long-term follow-up, three of 256 men have remained with testosterone levels in the castrate range. Similar highly significant results were seen in subgroup of 103 men who had both pre-LHRHa and follow-up hormone levels analysed (P=0.012, P<0.001, P<0.001 for testosterone, LH and FSH respectively). Our data suggest the possibility of residual gonadal dysfunction after short-term LHRHa administration and radical radiotherapy in localized prostate cancer. Serum testosterone levels are restored to normal levels in the majority of patients, with a compensatory increase in serum levels of LH.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Follicle Stimulating Hormone; Goserelin; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Neoadjuvant Therapy; Prostatic Neoplasms; Testosterone

We report a pilot study on a novel protocol of intermittent androgen deprivation (IAD) treatment of prostate cancer (PC), in which androgen deprivation is restarted when serum prostatic specific antigen (PSA) level reached more than 2 ng/ml and is stopped when PSA level decreased below 0.3 ng/ml. Thirty-two patients (aged 60 to 86 years, median 74 years) with prostate cancer (Stage A in 4 patients, B in 20, C in 1, D in 5, and relapse after radical prostatectomy in 2) were treated with IAD. Median serum PSA prior to the start of endocrine therapy was 15.65 (range 2.67 to 306.3) ng/ml. Eleven patients were treated with lutenizing-hormone-releasing hormone (LHRH) agonist alone and 21 were treated with LHRH agonist plus an antiandrogen. Median duration of first endocrine therapy was 572 (range 100 to 1,543) days. Median serum PSA at the start of first off-phase was 0.038 (range 0.003 to 0.489) ng/ml. After a median of 207 days (range 140 to 843) of follow-up, 19 patients were in the first cycle, 9 in the second cycle, 3 in the third cycle, 1 in the fourth cycle. Two patients developed androgen-independent PC. The median duration of first off-phase of IAD was 287 days. There was a significant inverse relation between the duration of the first on-phase and testosterone level measured 4 months after the cessation of first on-phase therapy (R = -0.518). These results suggest that our protocol provides a reasonable length of off-phase duration and that the long term-androgen deprivation phase might delay the recovery of the testicular endocrine function which should be maintained during the off-phase of IAD.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Nitriles; Pilot Projects; Prostatic Neoplasms; Tosyl Compounds

To determine the accuracy of combined magnetic resonance (MR) imaging and three-dimensional (3D) proton MR spectroscopic imaging in localizing prostate cancer to a sextant of the gland in patients receiving hormone deprivation therapy.. Combined MR imaging/3D MR spectroscopic imaging examinations were performed in 16 hormone-treated patients and 48 nontreated matched control patients before radical prostatectomy and step-section histopathologic analysis. At MR imaging, cancer presence within the peripheral zone was assessed on a per sextant basis by two readers. At 3D MR spectroscopic imaging, cancer was identified by using (choline plus creatine)-to-citrate ratios at cutoff values of 2 and 3 SDs above mean normal peripheral zone values. Data were compared by using receiver operating characteristic analysis.. There was no significant difference in the ability of combined MR imaging/3D MR spectroscopic imaging to localize prostate cancer in treated versus control patients. For MR imaging alone, the sensitivity and specificity were 91% and 48% (reader 1) and 75% and 60% (reader 2) in treated patients versus 79% and 60% (reader 1) and 84% and 43% (reader 2) in control patients. For 3D MR spectroscopic imaging alone (>3 SDs cutoff), higher specificity (treated, 80%; controls, 73%) but lower sensitivity (treated, 56%; controls, 53%) was attained. In treated patients, high sensitivity or specificity (up to 92%) was achieved when either or both modalities indicated cancer.. When performed within 4 months after initiating hormone deprivation therapy, combined MR imaging/3D MR spectroscopic imaging had the same accuracy in localizing prostate cancer as in nontreated patients.

Topics: Antineoplastic Agents, Hormonal; Case-Control Studies; Deuterium; Goserelin; Humans; Leuprolide; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Observer Variation; Prostatic Neoplasms; Reproducibility of Results

This report confirms experimental data on direct inhibitory effects of LH-RH agonists in growth control of human prostate cancer cells. The patient had hormone-refractory prostatic carcinoma after hormonal therapy, including orchiectomy, and responded successfully to a 6-month treatment with goserelin acetate (3.6 mg depot s.c.). The treatment has led to a reduction of tumor mass and metastases as well as an improvement in the patient's paraclinical indicators and general status. The remission lasted 14 months. The treatment still continues.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Drug Resistance, Neoplasm; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms

Fine-needle aspiration biopsy is a minimally invasive technique for obtaining sample material suitable not only for cytological grading but also for flow cytometry and for biochemical analyses. The prognostic value of tissue prostate-specific antigen (T-PSA) from fine-needle aspiration biopsies was compared with serum total and free prostate-specific antigen, the ratio of free:total serum prostate-specific antigen, tumor stage, cytological grade, and DNA ploidy in 179 patients with stage T2-T4 prostate cancer (CAP). The patients, who were free from bone metastases at the time of diagnosis, were treated by either orchidectomy or medical castration with GnRH analogues or high-dose parenteral depot estrogens. They were followed for at least for 71 months or until death, and the different variables were correlated to time to progression and time to death from CAP. Using Cox univariate analysis, T-PSA was shown to be the most important factor in predicting time to progression and time to death. When the patients were divided into three groups with respect to T-PSA, 56 of 60 (93%) of the patients with low T-PSA levels developed progressive disease, and 52 of 60 (87%) died of CAP. For patients with intermediate T-PSA levels, the corresponding figures were 9 of 60 (15%) and 6 of 60 (10%). None of the 59 patients with high T-PSA values developed progressive disease. Similar but less pronounced relationships were found between tumor progress and CAP-specific death on the one hand and clinical stage, cytological grade, and DNA ploidy on the other. In a Cox multivariate stepwise analysis, T-PSA was the only important factor for time to progression and death. This was also true for the subgroup of patients with stages T2 and T3 disease only. The study shows that T-PSA is superior to other hitherto routinely used markers for the prediction of outcome of hormone-treated patients with newly diagnosed CAP.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Biopsy, Needle; Disease Progression; Disease-Free Survival; Estradiol; Estradiol Congeners; Follow-Up Studies; Goserelin; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Predictive Value of Tests; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Regression Analysis; Survival Analysis; Time Factors

We report a case of the numb chin syndrome as the presenting symptom in a patient with metastatic prostate carcinoma. The numb chin syndrome is characterized by facial numbness along the distribution of the mental branch of the trigeminal nerve. Most cases of this syndrome that are not dental in origin have been associated with diffuse metastatic disease, particularly with underlying lymphoproliferative and breast cancer. Although axial and vertebral bone metastases are common in patients with carcinoma of the prostate, mental nerve involvement is rare. We present a case of the numb chin syndrome as the initial clinical manifestation in a patient with metastatic prostate adenocarcinoma.

Topics: Aged; Antineoplastic Agents, Hormonal; Biopsy; Carcinoma; Chin; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Hypesthesia; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Syndrome

Permanent androgen ablation has been the mainstay of treatment for advanced prostate cancer. However, the favorable outcome seen in recent pilot studies of intermittent androgen ablation raises the possibility of overtreatment.. This study included 35 Japanese men with advanced prostate cancer. Initial androgen ablation continued for 2 months after PSA levels decreased to <4.0 ng/ml, then was withdrawn. Androgen ablation was reinstituted 2 months after PSA reached levels >10 ng/ml, when indicated clinically or on patient request. Cycling continued until androgen independence was reached.. Mean follow-up was 21.0 months, representing an average of 2.5 cycles. Nine patients developed androgen independence at an average of 16.0 months following androgen ablation; three of these have died. Six of the nine patients with early biochemical progression had elevated alkaline phosphatase levels at entry; five of these exhibited a flare in alkaline phosphatase activity after initiation of androgen ablation. Mean bone mineral density (BMD) in the lumbar spines of 17 patients was 81.5 mg/cm3 at 23 months following therapy. The BMD of 10 of these patients was normal for their age. Four patients suffered bone fractures, none pathological.. Intermittent androgen ablation may be an option for patients with advanced prostate cancer and may be especially beneficial for those with initially low BMD levels. Patients with elevated alkaline phosphatase levels at entry or a flare in its activity may not be ideal candidates. Whether prolonging time to androgen independence will provide benefit remains to be investigated in a randomized, prospective study.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Disease Progression; Drug Administration Schedule; Flutamide; Follow-Up Studies; Fractures, Bone; Goserelin; Humans; Leuprolide; Lumbar Vertebrae; Male; Middle Aged; Pilot Projects; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Survival Rate; Testosterone; Treatment Outcome

The aim of this study was to determine the prevalence, severity and correlates of fatigue in a convenience sample of outpatients with prostate cancer prior to and following 3-months treatment with first-line hormone therapy (cyproterone acetate and goserelin). 'Severe fatigue' in the patients (n=62) was defined as a score on the Fatigue Severity Scale (FSS) greater than the 95th percentile of a group of elderly volunteers without cancer. Subjects also completed other questionnaires about fatigue and about quality of life, anxiety/depression and personality. Subjects underwent a nutritional assessment, tests of voluntary muscle function and attention. The prevalence of 'severe fatigue' at baseline was 8/58 (14%). Median FSS scores increased significantly after 3 months treatment. On multivariate analysis psychological distress explained 28% of the variance in fatigue scores. Treatment was associated with a reduction in voluntary muscle function, loss of muscle bulk, a decline in virility and potency, an improvement in pain and a reduction in nausea/vomiting. Fatigue is an important but under-recognised side-effect of hormone therapy.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cyproterone Acetate; Fatigue; Female; Goserelin; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Regression Analysis; Severity of Illness Index; Surveys and Questionnaires

The incidence of flutamide-induced liver toxicity was studied in 30 consecutive patients with prostate cancer who were treated with total androgen blockage (TAB) therapy (luteinizing hormone releasing hormone [LHRH] analogue and flutamide) in our hospital during the last 3 years and in 20 consecutive patients with prostate cancer who were treated by partial androgen blockage (PAB) therapy (LHRH analogue alone).. Liver function test, including measurement of serum levels of aspartate aminotransferase (AST) alanine aminotransferase (ALT), total cholesterol, total bilirubin, gamma-glutamyl transpeptidase (gamma-GTP), and cholinesterase were performed at regular interval.. The incidence of liver toxicity in patients receiving TAB (10 cases of 25 patients) was significantly higher than in patients receiving PAB (2 of 18 patients). Two patients in whom severe liver toxicity developed after receiving TAB were hospitalized. However, after flutamide was discontinued all patients with liver damage recovered with normalization of AST and ALT levels. Levels of total cholesterol and gamma-GTP did not differ significantly in either patient group. In two patients receiving TAB total bilirubin levels showed slight, transient elevations after maximum elevations of AST and ALT. In 80% of patients receiving TAB serum levels of cholinesterase were significantly higher than those in patients receiving PAB.. These data suggest that the risk of flutamide-induced liver toxicity is significant in patients receiving TAB. However, this damage can be normalized after flutamide has been discontinued. Serum levels of cholinesterase also increase significantly in patients receiving TAB. This previously unreported phenomenon suggests an unknown effect of flutamide on liver function in patients with prostate cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemical and Drug Induced Liver Injury; Cholinesterases; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Liver Diseases; Liver Function Tests; Male; Middle Aged; Prostatic Neoplasms

Luteinizing hormone-releasing hormone (LHRH) agonists are popularly used drugs in the treatment of prostatic cancer. However, it has been reported that continuation of a low testosterone level following a longterm administration of these drugs reduces the bone mineral density and makes for osteoporosis, which is accountable for fracture, we measured the bone mineral density and bone metabolic markers in the cases who suffered fracture receiving LHRH agonists for prostatic cancer.. Between 1994 and 1998, 196 patients (mean age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these patients, 13(7%) who had bone fracture during treated with LHRH agonists were divided into fracture group, and 70 patients who had not bone fracture divided into non-fracture group. Fracture by traffic accident was excluded. The bone density in the third lumbar vertebra was measured using quantitative computed tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were measured as bone metabolic markers.. The mean age of fractured cases was 78 years. The period from the start of treatment to fracture was 11 to 45 months (mean 27 months). No case of fracture at the site of metastasis of prostatic cancer was found. The bone density was significantly low in the fracture group compared with that of non-fracture group. Of the bone metabolic markers, NTx showed high values in the fracture group.. There is a need to measure bone mineral density and bone metabolic markers periodically and to evaluate secondary osteoporosis in the patients receiving LHRH agonists for prostatic cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Density; Fractures, Bone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Osteoporosis; Prostatic Neoplasms; Spine

Inappropriate antidiuretic hormone secretion (SIADH) may occur in a variety of diseases, including malignancies, and can be induced by drugs. We report a case of SIADH associated with prostatic carcinoma. A 50-year-old man was admitted to hospital with severe flank pain and weight loss. The diagnosis of SIADH syndrome and prostatic carcinoma was established, and hormonal therapy was instituted. However, the patient died in a month without any response to therapy. We conclude that prostatic carcinoma may cause SIADH and should therefore be considered in the differential diagnosis.

Topics: Abdominal Pain; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Diagnosis, Differential; Fatal Outcome; Goserelin; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Nitriles; Paraneoplastic Syndromes; Prostatic Neoplasms; Tosyl Compounds; Weight Loss

Recent studies have demonstrated that angiogenesis is a potent prognostic indicator for patients with prostate cancer (PCa) and have pointed out that the evaluation of vascular endothelial growth factor (VEGF) is useful in assessing the angiogenic phenotype in PCa. The aim of the study was to investigate immunohistochemically the expression of VEGF and its correlation with the pattern of capillary architecture in prostate cancer and high-grade prostatic intraepithelial neoplasia (PIN), in untreated and androgen-ablated patients.. Forty-five patients who underwent radical prostatectomy (RP) for localized prostate carcinoma were recruited for this study. The study population included two groups: 35 patients who did not receive chemo-, hormone, or radiation therapy before surgery, and 10 patients who were under complete androgen blockade (CAB) for 3 months at time of surgery. VEGF was examined by immunohistochemistry, and its tissue expression was compared with the pattern of capillary architecture evaluated by immunostaining the endothelial antigen CD34. The relationship of VEGF expression to chromogranin A-positive (e.g., neuroendocrine) cells was investigated.. In normal tissue, the intensity of the VEGF immunoreactivity in the cytoplasm of secretory cells ranged from negative to low. Very few basal cells stained for VEGF. All prostate cancer specimens stained positively, the intensity of the immunoreaction ranging from low to strong and being correlated with the Gleason score. Strongly positive VEGF immunoreactivity was detected in vascular endothelial cells and in stromal cells surrounding blood vessels. Two discrete immunostaining patterns were observed in high-grade PIN. VEGF expression of low-to-moderate intensity was defined as pattern A. The other, characterized by a strong cytoplasmic immunoreaction similar to that of poorly differentiated tumors, was defined as pattern B. The capillary architecture in high-grade PIN with pattern A was similar to the orderly vascular network seen in normal prostates, whereas in the pattern B it had the characteristics of microvessels usually seen in PCa. The degree of vascularization in the stroma adjacent to intensely VEGF-stained cells (neuroendocrine phenotype) was higher than that noted in association with secretory cells. CAB before surgery downregulated the expression of VEGF and decreased the degree of vascularization, except in the cell areas with neuroendocrine (NE) features.. Our immunohistochemical results indicate that significant levels of VEGF are present in prostate cancer and in a population of PIN lesions, expression being highest in association with NE cells. VEGF expression is downregulated by hormonal manipulation, except in the population of NE cells.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Combined Chemotherapy Protocols; Capillaries; Endothelial Growth Factors; Goserelin; Humans; Immunohistochemistry; Lymphokines; Male; Middle Aged; Neovascularization, Pathologic; Nitriles; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms; Tosyl Compounds; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

Several reports have described the antiandrogen withdrawal syndrome with various nonsteroidal antiandrogen agents. To our knowledge, there have been no reports describing a durable undetectable prostate-specific antigen (PSA) response with discontinuation of the antiandrogen agent bicalutamide (Casodex, Zeneca, Wilmington, DE, U.S.A.). We report a case in which a decline of serum PSA to undetectable levels was achieved with bicalutamide discontinuation.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Nitriles; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Substance Withdrawal Syndrome; Tosyl Compounds

To investigate the incidence of bone fractures in patients receiving luteinizing hormone-releasing hormone agonists (LHRH-a) for prostate cancer (in whom a continued low testosterone level after the long-term administration of these drugs reduces bone mineral density), and thus determine the risk of secondary osteoporosis.. Between 1994 and 1999, 218 patients (mean age 77.3 years) were treated for >/= 6 months with LHRH-a for prostate cancer; of these, 14 (6%) had a bone fracture during their treatment. Patients with fracture associated with motor vehicle accidents were excluded. The bone density in the third lumbar vertebra was meas-ured using quantitative computed tomography. Osteocalcin, 1,25-(OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone and calcitonin were measured as metabolic markers.. The mean age of the patients with fracture was 78 years; the mean (range) interval from the start of treatment to fracture was 28 (11-46) months. There was no case of a bone fracture at the site of a metastasis from prostate cancer. The bone density was significantly lower in the patients with a fracture than in those without. Of the bone metabolic markers, NTx was higher in those with a fracture.. There is a need to measure bone mineral density and bone metabolic markers periodically, and to evaluate secondary osteoporosis in patients receiving long-term LHRH-a for prostate cancer.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Antineoplastic Agents, Hormonal; Bone Density; Fractures, Spontaneous; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Lumbar Vertebrae; Male; Middle Aged; Prostatic Neoplasms; Risk Factors

(1) Goserelin, a GnRH agonist, has a new licensed indication in France, as an adjuvant to external radiotherapy for locally advanced prosate cancer. (2) The clinical file in this indication includes two trials of satisfactory methodological quality comparing radiotherapy + goserelin with radiotherapy alone. (3) In these trials the radiotherapy + goserelin combination increased the specific-symptom-free survival time. (4) In one trial goserelin caused endocrine disorders in 19% of patients. There were also more cases of urinary incontinence (13% in absolute values) among patients receiving the radiotherapy + goserelin combination. Furthermore, goserelin almost always causes impotence and reduced libido.

Topics: Aged; Antineoplastic Agents, Hormonal; Clinical Trials as Topic; Endocrine System Diseases; Erectile Dysfunction; France; Gonadotropin-Releasing Hormone; Goserelin; Humans; Libido; Male; Prostatic Neoplasms; Treatment Outcome; Urinary Incontinence

Patients with prostate cancer are treated with neoadjuvant, adjuvant and intermittent androgen deprivation therapy. Prostate specific antigen (PSA) is altered during androgen deprivation therapy, and as a result the prognostic significance and accuracy of PSA values measured before serum testosterone has normalized are questionable because the patient is still effectively on androgen deprivation therapy. We determine the time it takes for serum testosterone to return to normal after withdrawal of androgen deprivation therapy.. Serial serum testosterone was prospectively measured at 3-month intervals in 68 men after withdrawal of androgen deprivation therapy. The number of months to return to normal serum testosterone 270 ng./dl. or greater, was calculated for each patient. Patients were stratified according to duration of androgen deprivation, age and type of luteinizing hormone releasing hormone agonist used.. Median patient age was 71 years (range 46 to 88). Median time to normalization of testosterone was 7 months (range 1 to 58). At 3, 6 and 12 months 28%, 48% and 74% of men had normal serum testosterone, respectively. Serum testosterone took significantly longer to return to normal in patients on androgen deprivation therapy for 24 months or greater compared to those on therapy for less than 24 months (log-rank p = 0.0034). There was no statistical significance based on age or type of luteinizing hormone releasing hormone agonist used.. Androgen deprivation has an effect on serum testosterone that extends beyond the cessation of treatment. Serum testosterone should be measured in all men until normalization. These results should be applied to the interpretation of PSA levels after withdrawal of androgen deprivation therapy. In addition, these data have implications regarding dose scheduling and definition of biochemical (PSA) failure after primary therapy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Testosterone; Time Factors

We report the results of surgery in 520 patients with clinically localized carcinoma of the prostate (CaP) who received preoperative neoadjuvant hormonal therapy (NHT) for 3 to 11(+) months.. The results in the NHT patients were compared with those in 1,413 men having surgery without NHT at our institution during the same time period. In the group without pretreatment, the median and mean follow-up was 36 and 21 months, respectively. In the patients receiving NHT, the median follow-up was 33 months and the mean 41 months.. The overall disease-free survival (DFS) rate (serum prostate specific antigen [PSA] concentration < or = 0.2 ng/mL) was 75% at 5 years and 50% at 10 years. There was no statistically significant difference in overall DFS rate between men who had NHT and those who did not. No DFS advantage could be demonstrated for those patients with a presenting PSA >20 ng/mL who received NHT compared with patients with the same PSA concentration who did not receive NHT. Despite our previous experience indicating improved survival with NHT in men with a presenting PSA of > 10 ng/mL, we could find no advantage to NHT in enhancing DFS. At a median survival of 35 months (mean 41 months) in 201 men with an initial PSA > or = 10 ng/mL, 70% had an undetectable PSA concentration at 5 years compared with 72% at the same time point in men presenting with PSA <10 ng/mL. In the group expected to have the best surgical result; i.e. those men whose preoperative PSA was < or = 7 ng/mL, there was no DFS difference in men given NHT compared with those having no hormonal manipulation. Patients presenting with stage T(1) disease had a significantly better DFS than those with either T(2) or T(3) CaP. However, within each stage, the addition of NHT to surgery did not result in a higher DFS rate. The 5- and 10-year DFS rates for stage T(1) were 80% and 64%, for T2 disease 78% and 50%, and for T3 disease 67% and 50%. There was a statistically significant difference (P < or = 0.003) in survival between stage T(1) and stage T(2) disease, but no significant difference in DFS was noted in patients presenting with stage T(2) compared with T3 cancer (P = 0.431). Gleason score was not a significant predictor of durable DFS, and the addition of NHT did not improve the DFS within groups of patients with similar Gleason scores. Men with only one or two positive biopsy cores did significantly better than those with more than three positive cores (P = 0.06). There was a significant difference in DFS between men who had organ-confined disease and those with disease outside the gland (P = 0.0003). However, NHT did not improve DFS. The presence of positive surgical margins was a negative prognostic factor (P = 0. 001). Men who received NHT had a statistically lower positive margin rate (P = 0.001), but NHT did not increase the likelihood of a durable DFS (P = 0.175). The duration of NHT did not affect the DFS (P = 0.100 for <3 v >3 months).. There appears to be no subset of men undergoing radical prostatectomy in whom the routine administration of NHT is beneficial despite the statistically significant improvement in the pathologic findings.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents, Hormonal; Biopsy; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Disease-Free Survival; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Time Factors

In hemodialysis patients, few cases of prostate cancer have been reported until recently. We present a case of prostate cancer with multiple lung metastases in a chronic hemodialysis patient. A 65-year-old Japanese man who had maintained hemodialysis for 5 years was referred to our hospital with multiple metastatic lung tumors. Serum prostate tumor markers were highly elevated although his plasma testosterone level was within the normal range. A transrectal needle prostate biopsy confirmed a histologic diagnosis of moderately differentiated adenocarcinoma. Androgen blockade therapy was very effective as evidenced by a quick decrease of serum tumor markers. The follow-up computed tomography scan of the chest performed 3 months later showed a complete disappearance of the coin lesions. The early detection of prostate cancer in hemodialysis patients is difficult because of a lack of urologic symptoms, which indicate the importance of periodic screening by serum tumor markers. Combined androgen blockade is effective even in hemodialysis patients. However, close follow up is necessary because long-term results and prognoses are still unknown.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Lung Neoplasms; Male; Prostatic Neoplasms; Radiography, Thoracic; Renal Dialysis; Tomography, X-Ray Computed

We have previously shown that LHRH agonists exert a direct and specific inhibitory action on the proliferation of the androgen-independent DU 145 prostate cancer cell line; however, the cellular mechanisms mediating this antiproliferative action are not well defined. It is well known that the insulin-like growth factor (IGF) system plays a crucial role in the local regulation of the growth of androgen-independent prostate cancer. The present experiments were performed to evaluate whether LHRH agonists might exert their antimitogenic effect by interfering with the activity of the locally expressed IGF system. To this purpose, the effects of the LHRH agonist Zoladex (LHRH-A) on 1) the mitogenic action of IGF-I, 2) the tyrosine phosphorylation of type 1 IGF-I receptor (IGF-IR), 3) the concentration of IGF-IR, and 4) the secretion of IGF-binding protein-3 were studied. The results obtained show that in DU 145 cells, LHRH-A 1) counteracts the mitogenic action of IGF-I in a dose-dependent manner, 2) prevents the IGF-I-induced tyrosine phosphorylation of the IGF-IR, 3) reduces the concentration of IGF-IR without affecting its Kd value, and 4) does not affect the secretion of IGF-binding protein-3 in the conditioned medium from these cells. These data suggest that LHRH agonists may inhibit the proliferation of human androgen-independent prostate tumor cells by interfering with some of the cellular mechanisms mediating the stimulatory action of the IGF system.

Topics: Blotting, Western; Cell Division; Gonadotropin-Releasing Hormone; Goserelin; Humans; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Prostatic Neoplasms; Somatomedins; Tumor Cells, Cultured; Tyrosine

In order to evaluate the prognostic value of tissue-PSA (prostatic-specific protein, measured in aspiration biopsies) 231 hormonally treated patients with verified carcinoma of the prostate (CaP) but without metastasis were studied retrospectively. T-PSA was determined at the time of diagnosis in all patients and in 52 of these also at 6, 12 and 24 months after diagnosis. Of the 231 patients, 79 died of prostatic carcinoma and 152 were still alive or had died of other diseases at the end of the observation period (more than 71 months). In a first set of evaluations the predictive value of a single analysis at the time of diagnosis was studied in 179 patients. It was found that tissue PSA was the most important factor for predicting both time to progression and time to death in CaP. Other competing factors were S-PSA, free S-PSA, age, clinical stage, grade and DNA-ploidy. Further evaluations regarding serial PSA determinations were performed in 52 patients. Tissue PSA increased during treatment in all patients who died of CaP. In all patients who survived or died for other reasons, tissue PSA decreased during treatment and remained low. The change of tissue PSA seen between 0, 6 and 12 months could in all cases predict the clinical outcome. It is concluded that a single analysis of tissue PSA at the time of diagnosis can predict the clinical outcome in most cases and that serial determinations can predict the outcome in almost all cases of a CaP without metastasis at the time of diagnosis. This requires that we use this assay when selecting between patients who will survive on hormonal treatment and those who most probably would benefit from a more aggressive treatment.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Biopsy, Needle; Carcinoma; Estradiol; Estradiol Congeners; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Treatment Outcome

To identify and describe the frequency and severity of hepatotoxicity in patients who received flutamide therapy for prostate cancer, 22 patients were treated with the combination of flutamide and goserilin or orchiectomy. After diagnosis and staging of prostate cancer, baseline results were obtained for a set of five liver function tests (LF Ts). Hepatotoxicity was assessed according to the WHO criteria. After initiation of flutamide therapy, LF Ts were performed at 4, 8 and 12 weeks and every 2 months thereafter. Severe hepatotoxicity appeared in two of 22 (9%) patients. Following the discontinuation of flutamide, one patient died due to acute liver failure. On the other patient an improvement of LF Ts occurred after cessation of flutamide. The observed severe hepatotoxicity in two of 22 (9%) patients occurred more frequent than is predicted in the literature. Patients treated with flutamide, having symptomatic or asymptomatic liver enzyme elevations, should be taken off therapy as soon as possible.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Contraindications; Flutamide; Goserelin; Humans; Liver; Liver Failure, Acute; Liver Function Tests; Male; Middle Aged; Orchiectomy; Prospective Studies; Prostatic Neoplasms

Topics: Antineoplastic Agents, Hormonal; Drug Administration Schedule; Goserelin; Humans; Leuprolide; Male; Neoadjuvant Therapy; Prostatic Neoplasms; Testosterone; Time Factors

Topics: Antineoplastic Agents, Hormonal; Drug Administration Schedule; Goserelin; Humans; Leuprolide; Male; Neoadjuvant Therapy; Prostatic Neoplasms; Testosterone; Time Factors

The purpose of the study was to examine the immunohistochemical stainability of prostate-specific antigen (PSA) and androgen receptor (AR) in biopsies from localised prostate cancers before treatment, after androgen deprivation and after radiation therapy.. Biopsies were taken from 16 men with prostate cancer (T1-3,Nx,M0) before the start (START) of androgen deprivation with LHRH analogue, during the following pelvic lymph node dissection (PLND), and twice after radiotherapy (POSTRAD and FINAL).. Malignant cells were observed in all START, PLND and POSTRAD biopsies and in 6 of 7 FINAL specimens. During androgen suppression and subsequent radiotherapy a gradual reduction in tissue immunoreactivity for PSA and AR was observed paralleled by a reduction in serum PSA. The most striking observation was the complete lack of AR stainability after combined LHRH/radiation therapy. Of the 7 patients who had a long-term follow-up after radiotherapy, 1 patient was cancer negative on biopsy and without AR and PSA stainability. Six patients with cancer-positive FINAL biopsies had regained AR stainability. Five of these latter biopsies also stained for PSA. Five of the six patients had no elevation in serum PSA.. After combined hormone/radiotherapy serum PSA is a relatively unreliable marker for the demonstration of residual cancer. This combination therapy leads to transient loss of immunohistochemically stained tissue PSA and AR in the residual cancer.

Topics: Aged; Androgen Antagonists; Biopsy, Needle; Combined Modality Therapy; Goserelin; Humans; Immunohistochemistry; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Receptors, Androgen; Retrospective Studies; Sensitivity and Specificity

To determine the change in volume of the prostate as a result of neoadjuvant androgen deprivation prior to prostate implant and in the early postimplant period following transperineal ultrasound guided palladium-103 brachytherapy for early-stage prostate cancer.. Sixty-nine men received 3 to 6 months of androgen deprivation therapy followed by treatment planning ultrasound followed 4 to 8 weeks later by palladium-103 implant of the prostate. All patients had clinical and radiographic stage T1c-T2b adenocarcinoma of the prostate. A second ultrasound study was carried out 11 to 13 days following the implant to determine the change in volume of the prostate as a result of the implant. The prehormonal and preimplant volumes were compared to the postimplant volume to determine the effect of hormones and brachytherapy on prostate volume.. The median decrease in prostate volume as a result of androgen deprivation was 33% among the 54 patients with prostate volume determinations prior to hormonal therapy. The reduction in volume was greatest in the quartile of men with the largest initial gland volume (59%) and least in the quartile of men with smallest glands (10%). The median reduction in prostate volume between the treatment planning ultrasound and the follow-up study after implant was 3%, but 23 (33%) patients had an increase in prostate volume, including 16 (23%) who had an increase in volume >20%; 11 of these patients (16%) had an increase in volume >30%. The time course of development and resolution of this edema is not known. The severity of the edema was not related to initial or preimplant prostate volume or duration of hormonal therapy.. Prostate edema may significantly affect the dose delivered to the prostate following transperineal ultrasound guided brachytherapy. The effect on the actual delivered dose will be greater when shorter lived isotopes are used. It remains to be observed whether this edema will affect outcome.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Brachytherapy; Combined Modality Therapy; Dose-Response Relationship, Radiation; Goserelin; Humans; Iodine Radioisotopes; Leuprolide; Male; Palladium; Prostatic Neoplasms; Radiopharmaceuticals; Ultrasonography, Interventional

We reviewed our institution's experience treating patients with prostate cancer with 3-dimensional conformal radiation therapy (3DCRT) and short-term adjuvant hormonal therapy to determine biochemical no evidence of disease (bNED) and clinical outcome compared with patients treated with 3DCRT alone. Between 4/1/89 and 11/30/94, 558 patients with clinically localized prostate cancer received treatment at Fox Chase Cancer Center (Philadelphia, Pa.); 484 patients were treated with 3DCRT alone (Group I); 74 patients were treated with 3DCRT and hormones (Group II). Five-year actuarial rates of bNED control, distant metastasis-free survival (DMFS), cause-specific survival (CSS), and overall survival (OS) were calculated for pretreatment PSA, Gleason score, T stage, use of hormones, treatment field size, age, and dose. A matched case/control analysis was performed to further evaluate the effect of hormones on treatment with 3DCRT. Median follow-up was 47 months (range: 2-97 months). The 5-year actuarial rates of bNED control, DMFS, CSS, and OS were 66%, 93%, 98%, and 86%, respectively, for Group I patients and 68%, 93%, 98%, and 89%, respectively, for Group II patients. Multivariate analysis demonstrated that hormone use was an independent predictor of bNED control only. A significant difference in bNED control was observed between Group I and II (43% vs. 71%) using the matched case/control analysis (P = 0.02). A trend towards significance was observed for different rates of DMFS between Group I and II (79% vs. 94%, P = 0.09). Patients with clinically localized prostate cancer with poor prognostic features (pretreatment PSA > or = 10 ng/ml, Gleason score > or = 7, and/or T2c or greater palpation stage) show improved rates of bNED control and a trend towards improved DMFS when treated with 3DCRT and short-term adjuvant hormones compared with 3DCRT alone. Long-term observation will be necessary to see if improvements in bNED control will translate into improvements in overall survival.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Disease-Free Survival; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Radiotherapy, Conformal; Retrospective Studies; Survival Rate; Treatment Outcome

A 72-year-old man presented with pollakiuria and dysuria. His prostate was the size of an apple and hard on digital rectal examination and the serum prostate specific antigen (PSA) level was 73 ng/ml (RIA). Ultrasonography revealed bilateral hydronephrosis and the serum creatinine level was 13.2 mg/dl. CT scanning of the abdomen demonstrated swelling of paraaortic lymph nodes. Transrectal needle biopsy of the prostate gave a diagnosis of moderately differentiated adenocarcinoma. Accordingly, the final diagnosis was prostate cancer (cT3N4M1, stage D2). Immediately after bilateral percutaneous nephrostomy, treatment with an LH-RH agonist (goserelin) and flutamide was commenced. Serum creatinine was 6.6 mg/dl at the start of antiandrogen therapy and decreased to 1.8 mg/dl after 27 days. A 125 mg flutamide capsule was administered at 7 a.m., and blood samples were collected 4 hours later on days 1, 2, 3, 5, 6, 8, 12, 14, 17, 18 and 27. The OH-flutamide concentration was measured. There was no significant correlation between serum creatinine and the OH-flutamide concentration. After implantation of goserelin (3.6 mg depot), blood samples were obtained at 11 a.m. on days 8, 12, 14, 15 and 25. The serum goserelin level was measured. The serum goserelin level increased to a peak on day 14, as described previously, but the peak value of 9.63 ng/ml was higher than that reported before (mean +/- SD 2.848 +/- 0.199).

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Goserelin; Humans; Hydronephrosis; Male; Prostatic Neoplasms; Ureteral Obstruction

Evidence has accumulated indicating that LHRH might behave as an autocrine/paracrine growth inhibitory factor in some peripheral tumors. However, LHRH receptors in tumor cells have not been fully characterized, so far. The present experiments were performed to analyze: 1) the messenger RNA expression; 2) the molecular size; and 3) the signal transduction pathway of LHRH receptors in prostate cancer. For these studies, the human androgen-dependent LNCaP and androgen-independent DU 145 prostate cancer cell lines were used. 1) By RT-PCR, a complementary DNA product, which hybridized with a 32P-labeled oligonucleotide probe specific for the pituitary LHRH receptor complementary DNA, was found both in LNCaP and in DU 145 cells. 2) Western blot analysis, using a monoclonal antibody raised against the human pituitary LHRH receptor, revealed the presence of a protein band of approximately 64 kDa (corresponding to the molecular mass of the pituitary receptor) in both cell lines. 3) In LNCaP and DU 145 cells, pertussis toxin completely abrogated the antiproliferative action of a LHRH agonist (LHRH-A). Moreover, LHRH-A substantially antagonized the pertussis toxin-catalyzed ADP-ribosylation of a Galpha(i) protein. Finally, LHRH-A significantly counteracted the forskolin-induced increase of intracellular cAMP levels in both cell lines. These data demonstrate that the LHRH receptor, which is present in prostate cancer cells, independently of whether they are androgen-dependent or not, corresponds to the pituitary receptor, in terms of messenger RNA expression and protein molecular size. However, at variance with the receptor of the gonadotrophs, prostate cancer LHRH receptor seems to be coupled to the Galpha(i) protein-cAMP signal transduction pathway, rather than to the Galpha(q/11)-phospholipase C signaling system. This might be responsible for the different actions of LHRH in anterior pituitary and in prostate cancer.

Topics: Adenosine Diphosphate Ribose; Animals; Blotting, Western; Cyclic AMP; Gene Expression; Goserelin; GTP-Binding Protein alpha Subunits, Gi-Go; Humans; Male; Molecular Weight; Pertussis Toxin; Pituitary Gland; Prostatic Neoplasms; Rats; Rats, Sprague-Dawley; Receptors, LHRH; RNA, Messenger; Signal Transduction; Tumor Cells, Cultured; Type C Phospholipases; Virulence Factors, Bordetella

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Randomized Controlled Trials as Topic

The objective of this study was to elucidate the mechanism underlying the further suppression of serum testosterone (T) by diethylstilbestrol diphosphate (DES-DP) in patients with prostate cancer refractory to hormonal treatment. These patients received an LHRH agonist with or without a non-steroidal androgen-receptor blocker or a gestagen before DES-DP. We measured serum levels of total and free T, dihydrotestosterone (DHT), estradiol (E2), dehydroepiandrosterone sulfate (DHEA-S), dehydroepiandrosterone (DHEA), androstenedione, cortisol, aldosterone before and during intravenous administration of high doses of DES-DP (500 or 1000 mg/day). DES-DP administration suppressed the serum levels of FSH (p=0.04) and total T (p=0.02), and eliminated free T (p=0.04) and E2 (p=0.04) from serum, while reducing serum DHEA-S to approximately two-thirds of the pretreatment level (p=0.03). In contrast, serum levels of SHBG (p=0.02) and cortisol (p=0.02) were markedly increased after DES-DP administration. The latter had no significant effect on serum levels of LH, DHT, ACTH, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, DHEA, androstenedione, or aldosterone. The results suggest that the potent suppression of circulating total T by DES-DP is caused, in part, by the inhibitory effect of DES-DP on serum DHEA-S level. In most patients, high-dose DES-DP treatment completely suppressed the serum level of free T, while possibly elevating serum SHBG and decreasing serum total T. The mechanisms that maintain the serum level of serum DHT during DES-DP treatment require further elucidation.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents; Chlormadinone Acetate; Dehydroepiandrosterone Sulfate; Diethylstilbestrol; Drug Resistance, Neoplasm; Estradiol; Follicle Stimulating Hormone; Goserelin; Hormones; Humans; Hydrocortisone; Leuprolide; Male; Middle Aged; Progesterone Congeners; Prostatic Neoplasms; Sex Hormone-Binding Globulin; Testosterone

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Biopsy; Flutamide; Goserelin; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Topics: Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Humans; Male; Prostatic Neoplasms

Experiments have been performed to clarify whether LHRH agonists might decrease growth of hormone-unresponsive prostate cancer in vivo. Male nude mice were injected s.c. with the human androgen-independent prostate tumor DU 145 cells; osmotic minipumps releasing the LHRH agonist Zoladex (LHRH-A) for 14 days were simultaneously implanted under the skin. Treatment with LHRH-A induced a significant decrease in tumor growth up to the end of the treatment. In subsequent experiment, minipumps releasing LHRH-A were implanted in nude mice either 7 or 14 days after cell inoculation. When the treatment was started 7 days after inoculation of the cells, tumor growth was significantly decreased up to 28 days; thereafter, tumor volume remained lower than in controls, although not significantly. When LHRH-A was administered beginning 14 days after cell inoculation, tumor growth was not significantly affected at any time interval considered. LHRH-A did not appear to induce apoptosis in DU 145 cells, at least on the basis of the apoptotic index and immunohistochemical staining of the p53 protein. On the other hand, treatment with LHRH-A was accompanied by a significant decrease of the concentration of epidermal growth factor receptors in DU 145 prostate cancer specimens. Our results show that the LHRH agonist used significantly inhibits the growth of DU 145 androgen-independent prostate tumor xenografts in nude mice.

Topics: Animals; Antineoplastic Agents, Hormonal; Apoptosis; Gonadotropin-Releasing Hormone; Goserelin; Male; Mice; Mice, Nude; Mitotic Index; Neoplasm Transplantation; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Time Factors; Tumor Cells, Cultured

Androgen receptor blocking agents have become an established form of therapy for men with disseminated prostate carcinoma. The purpose of this study was to evaluate markers of bone turnover and to measure bone mineral densities (BMD) in men with disseminated prostate carcinoma treated with combined androgen blockade prior to and after 6 months of intermittent cyclic etidronate therapy.. Twelve consecutive men with disseminated prostate carcinoma were evaluated at 0, 6, and 12 months after treatment with a long acting gonadotropin-releasing hormone agonist (goserelin acetate) and an androgen antagonist (flutamide). During the 6-12 month period, patients were treated with adjuvant intermittent cyclic etidronate therapy and calcium supplementation. Lumbar spine BMD was measured by spinal quantitative computed tomography (QCT) and femoral neck BMD by dual energy X-ray absorptiometry (DXA).. Combined androgen blockade resulted in all men achieving serum free testosterone concentrations of <2.2 pmol/L (normal range, 38-114 pmol/ L). The mean serum prostate specific antigen activities decreased from 130.8+/-46 to 6.9+/-4.4 ng/mL (P < 0.05). Although serum calcium, parathyroid hormone, and 25-hydroxyvitamin D measurements remained unchanged, serum bone Gla-protein concentrations and urinary deoxypyridinolene excretion rates increased significantly (P < 0.01, respectively). Mean lumbar spine QCT decreased by 6.6+/-1.5% from 76.5 mg/cm3 (95% confidence interval [95% CI, 57-96 mg/cm3) to 73.9 mg/cm3 (95% CI, 55-93 mg/cm3) (P < 0.001) and mean femoral neck DXA decreased by 6.5+/-1.3% from 0.94 g/cm2 (95% CI, 0.81-1.07 g/cm2) to 0.91 g/cm2 (95% CI, 0.79-1.04 g/cm2) (P < 0.001). After treatment with adjuvant intermittent cyclic etidronate, mean lumbar spine QCT increased by 7.8+/-3.7% to a final value of 75 mg/cm3 (95% CI, 48.7-101 mg/cm3) (P=0.001 compared with the initial 6 months without intermittent cyclic etidronate therapy). Significant increases in BMD also were observed in the femoral neck and Ward's triangle.. Androgen receptor blocking agents have an established role in the treatment of disseminated prostate carcinoma. However, combined androgen blockade in elderly men with disseminated prostate carcinoma results in high bone turnover with significant cancellous bone loss. The results of this study show that adjuvant therapy with intermittent cyclic etidronate may prevent these changes and decrease the risk of spinal fractures.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Amino Acids; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bone and Bones; Bone Density; Calcium; Carcinoma; Drug Administration Schedule; Etidronic Acid; Evaluation Studies as Topic; Femur Neck; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Longitudinal Studies; Lumbar Vertebrae; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Testosterone; Tomography, X-Ray Computed; Vitamin D

It is well known that androgens play an important role in bone metabolism and male hypogonadism induce osteoporosis. Luteinizing hormone-releasing hormone analogue (LHRH-a) which is essential for conservative therapy of prostatic carcinoma (CaP) ultimately reduces circulating testosterone to castration levels. The purpose of this study was to determine the risk of decrease of bone mineral density in men receiving LHRH-a for CaP.. Fifty-three man with CaP aged 63 to 95 years (mean 75.5 years) were included in this study. Seven patients received LHRH-a with estrogen drug, forty-six patients received LHRH-a with or without anti androgen drug. To estimate patient's bone density we use the second metacarpal bone density using a microdensitometry method.. Blood level of sex hormone of the forty-six patients who were received LHRH-a without estrogen, was the same as that of castration. Patients who were treated more than twelve months had less bone density than patients who were treated less than eleven months. As the duration of medical castration period was prolonged, patients bone density were reduced. Whereas seven patients who received estrogen drug did not find a decrease of bone density regardless of duration of treatment period.. Hypogonadism induced LHRH-a also reduce bone density, so there is a risk of iatrogenic osteoporosis caused by therapy for CaP with LHRH-a. Patients with osteoporosis easily suffer from a much complicated and pernicious bone fracture, so we should measure bone density of male patients same as female treated with LHRH-a for a long-term.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Density; Estrogens; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Prostatic Neoplasms; Risk

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Prostatic Neoplasms

The p53 tumor suppressor gene (also known as TP53) is one of the most frequently mutated genes in human cancer. Several studies have shown that p53 mutations are infrequent in prostate cancer and are associated with advanced disease.. We assessed the prognostic value of identifying abnormal p53 protein expression in the tumors of patients with locally advanced prostate cancer who were treated with either external-beam radiation therapy alone or total androgen blockade before and during the radiation therapy.. The study population consisted of a subset of patients entered in Radiation Therapy Oncology Group protocol 8610 ("a phase III trial of Zoladex and flutamide used as cytoreductive agents in locally advanced carcinoma of the prostate treated with definitive radiotherapy"). Immunohistochemical detection of abnormal p53 protein in pretreatment specimens (i.e., needle biopsies or transurethral resections) was achieved by use of the monoclonal anti-p53 antibody DO7; specimens in which 20% or more of the tumor cell nuclei showed positive immunoreactivity were considered to have abnormal p53 protein expression. Associations between p53 protein expression status and the time to local progression, the incidence of distant metastases, progression-free survival, and overall survival were evaluated in univariate (logrank test) and multivariate (Cox proportional hazards model) analyses. Reported P values are two-sided.. One hundred twenty-nine (27%) of the 471 patients entered in the trial had sufficient tumor material for analysis. Abnormal p53 protein expression was detected in the tumors of 23 (18%) of these 129 patients. Statistically significant associations were found between the presence of abnormal p53 protein expression and increased incidence of distant metastases (P = .04), decreased progression-free survival (P = .03), and decreased overall survival (P = .02); no association was found between abnormal p53 protein expression and the time to local progression (P = .58). These results were independent of the Gleason score and clinical stage. A significant treatment interaction was detected with respect to the development of distant metastases: Among patients receiving both radiation therapy and hormone therapy, those with tumors exhibiting abnormal p53 protein expression experienced a reduced time to the development of distant metastases (P = .001); for patients treated with radiation therapy alone, the time to distant metastases was unrelated to p53 protein expression status (P = .91).. Determination of p53 protein expression status yield significant, independent prognostic information concerning the development of distant metastases, progression-free survival, and overall survival for patients with locally advanced prostate cancer who are treated primarily with radiation therapy.. The interaction of radiation therapy plus hormone therapy and abnormal p53 protein expression may provide a clinical link to experimental evidence that radiation therapy and/or hormone therapy act, at least in part, by the induction of apoptosis (a cell death program) and suggests that this mechanism may be blocked in patients whose tumors have p53 mutations.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Disease Progression; Disease-Free Survival; Flutamide; Gene Expression Regulation, Neoplastic; Genes, p53; Goserelin; Humans; Male; Middle Aged; Mutation; Prognosis; Prostatic Neoplasms; Radiotherapy, Adjuvant; Survival Analysis; Tumor Suppressor Protein p53

It is unclear if continuing with androgen deprivation in hormone-refractory prostate cancer is of any benefit. We report here 3 cases where continuation of androgen deprivation was essential in maintaining the response to chemotherapy.. In the 3 patients there was an initial response to chemotherapy before relapse, as assessed by prostate-specific antigen levels. However, restarting the previously ineffective hormone therapy resulted in continued response to chemotherapy.. In some patients continued androgen deprivation is essential to the response to chemotherapy. Presumably, in hormone-relapsed disease a significant proportion of the tumour can still be responsive to androgen deprivation.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diethylstilbestrol; Disease Progression; Epirubicin; Fluorouracil; Goserelin; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms

To assess the factors that predict late GI and GU morbidity in radiation treatment of the prostate.. Seven hundred twelve consecutive prostate cancer patients treated at this institution between 1986 and 1994 (inclusive) with conformal or conventional techniques were included in the analysis. Patients had at least 3 months follow-up and received at least 65 Gy. Late GI Grade 3 morbidity was rectal bleeding (requiring three or more procedures) or proctitis. Late Grade 3 GU morbidity was cystitis or stricture. Multivariate analysis (MVA) was used to assess factors related to the complication-free survival. The factors assessed were age, occurrence of side effects > or = Grade 2 during treatment, irradiated volume parameters (use of pelvic fields, treatment of seminal vesicles to full dose or 57 Gy, and use of additional rectal shielding), dose, comorbidities, and other treatments (hormonal manipulation, TURP).. Acute GI and GU side effects (Grade 2 or higher) were noted in 246 and 201 patients, respectively; 67 of these patients exhibited both. GI side effects were not correlated with GU side effects acutely. Late and acute morbidities were correlated (both GI and GU). Fifteen of the 712 patients expressed Grade 3 or 4 GI injuries 3 to 32 months after the end of treatment, with a mean of 14.3 months. One hundred fifteen patients expressed Grade 2 or higher GI morbidity (mean: 13.7 months). The 43 Grade 2 or higher GU morbidities occurred significantly later (mean: 22.7 months). Central axis dose was the only independent variable significantly related to the incidence of late GI morbidity on MVA. No treatment volume parameters were significant for Grade 3. The following parameters were significantly related (by MVA) to Grade 2 GI morbidity: central axis dose, use of the increased rectal shielding, androgen deprivation therapy starting before RT. Acute and late GI morbidities were highly correlated. History of diabetes, treatment of pelvic nodes, and age less than 60 years were significantly related to acute GI side effects. The parameters significantly related to late Grade 2 or higher GU morbidity were central axis dose, androgen deprivation therapy (Zoladex or Lupron) prior to radiation therapy (RT), history of obstructive symptoms, and acute GU side effects. There were too few late Grade 3 GU morbidities to perform multivariate analysis. Acute GU side effects were highly correlated with late GU injury. The following were correlated with acute GU side effects: history of diabetes (+), treatment with conformal fields (-), TURP before RT (-), presentation with urinary obstructive symptoms.. Both late GI and GU morbidity demonstrate a dose dependence, but only the volume dependence observed is a reduction in late Grade 2-4 GI morbidity by increasing the rectal shielding in the lateral fields for the final 10 Gy. Moreover, both late GI and GU morbidity was increased in patients treated with hormone manipulation prior to RT. GI and GU injuries were correlated with their corresponding acute side effects. GI and GU complications must not be combined for analysis to determine the factors related to their occurrence.

Topics: Antineoplastic Agents, Hormonal; Digestive System; Dose-Response Relationship, Radiation; Goserelin; Humans; Leuprolide; Male; Middle Aged; Morbidity; Multivariate Analysis; Prostatic Neoplasms; Radiation Injuries; Risk Factors; Time Factors; Urogenital System

Topics: Antineoplastic Agents, Hormonal; Bone Neoplasms; Goserelin; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Testosterone

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Bone Neoplasms; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Failure

In the light of a case of left orbital metastasis, constituting the presenting sign of prostatic cancer in a 60-year-old man, the authors emphasize the rarity of this site, despite the high frequency of bone metastases in this disease. They discuss the diagnostic methods and stress the need for urgent treatment to save ocular function.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Diethylstilbestrol; Emergencies; Goserelin; Humans; Injections, Intravenous; Male; Methylprednisolone Hemisuccinate; Middle Aged; Orbital Neoplasms; Prostatic Neoplasms; Vision, Ocular

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Goserelin; Humans; Male; Middle Aged; Palliative Care; Penile Neoplasms; Prostatic Neoplasms

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Goserelin; Humans; Male; Prostatic Neoplasms; Survival Analysis

Cooperative groups have investigated the outcome of androgen deprivation therapy combined with radiation therapy in prostate cancer patients with variable pretreatment prognostic indicators. This report describes an objective means of selecting patients for adjuvant hormonal therapy by a retrospective matched case/control comparison of outcome between patients with specific pretreatment characteristics who receive adjuvant hormones (RT+H) vs. patients with identical pretreatment characteristics treated with radiation therapy alone (RT). In addition, this report shows the 5-year bNED control for patients selected by this method for RT+H vs. RT alone.. From 10/88 to 12/93, 517 T1-T3 NXM0 patients with known pretreatment PSA level were treated at Fox Chase Cancer Center. Four hundred fifty-nine of those patients were treated with RT alone while 58 were treated with RT+H. The patients were categorized according to putative prognostic factors indicative of bNED control, which include the palpation stage, Gleason score, and pretreatment PSA. We compared actuarial bNED control rates according to treatment group within each of the prognostic groups. In addition, we devised a retrospective matched case/control selection of RT patients for comparison with the RT+H group. Five-year bNED control was compared for the two treatment groups, excluding the best prognosis group, using 56 RT+H patients and 56 matched (by stage, grade, and pretreatment PSA level) controls randomly selected from the RT alone group. bNED control for the entire group of 517 patients was then analyzed multivariately using step-wise Cox regression to determine independent predictors of outcome. Covariates considered for entry into the model included stage (T1/T2AB vs. T2C/T3), grade (2-6 vs. 7-10), pretreatment PSA (0-15 vs. > 15), treatment (RT vs. RT+H), and center of prostate dose. bNED failure is defined as PSA > or = 1.5 ngm/ml and rising on two consecutive determinations. The median follow-up for the 112 matched case/control patients was 41 months. The median follow-up was 46 months for the RT (range 11-102 months) and 37 months for the RT+H group (range 6-82 months).. Univariate analysis according to treatment for the prognostic factors of palpation stage, Gleason score, and pretreatment PSA demonstrates a significant improvement in 3-year bNED control with the addition of hormones for patients with T2C/T3, Gleason score 7-10, or pretreatment PSA > 15 ngm/ml. A comparison of bNED control according to treatment demonstrates improvement in 5-year bNED control of 55% for patients treated with RT+H vs. 31% for those patients treated with RT alone (p = 0.0088), although there is not a survival advantage. Multivariate analysis demonstrates that hormonal treatment is a highly significant independent predictor of bNED control (p = 0.0006) along with pretreatment PSA (p = 0.0001), palpation stage (p = 0.0001), grade (p = 0.0030), and dose (p = 0.0001).. (1) Patients with specific adverse pretreatment prognostic factors (i.e., T2C/T3, Gleason score 7-10, pretreatment PSA > 15) benefit from adjuvant hormonal therapy. (2) Upon multivariate analysis, hormonal therapy is determined to be a highly significant predictor of bNED control, after adjusting for all other covariates. (3) The 5-year bNED control rates of 55% for RT+H vs. 31% for RT alone represents the magnitude of benefit from adjuvant hormone therapy. (4) The bNED control curves are separated by about 20 months, representing a delay in disease progression with adjuvant hormonal therapy, as there is no overall survival difference.

Topics: Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Case-Control Studies; Combined Modality Therapy; Flutamide; Goserelin; Humans; Leuprolide; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies

Luteinizing Hormone Releasing Hormone (LHRH) agonists exert both "in vitro" and "in vivo" a direct inhibitory action on the growth of both androgen-dependent (LNCaP) and androgen-independent (DU 145) human prostatic cancer cell lines. The present experiments have been performed to investigate the mechanisms involved in this direct antiproliferative action of LHRH agonists. In particular, the aim was to study whether these compounds might exert their antiproliferative effect by interfering with the stimulatory action of epidermal growth factor (EGF) both "in vitro" and "in vivo". To this purpose, the effects of LHRH agonist, Zoladex (LHRH-A), on the mitogenic action of EGF, on EGF-activated intracellular signaling mechanisms (tyrosine phosphorylation of EGF receptor and c-fos proto-oncogene expression), and on the concentration of EGF receptors have been evaluated in both LNCaP and DU 145 cells. The results of these "in vitro" studies show that in LNCaP cells LHRH-A counteracts the mitogenic action of EGF, abrogates the EGF-induced c-fos expression and reduces the concentration of EGF-binding sites, without modifying the EGF induced tyrosine phosphorylation. In DU 145 cells, LHRH-A antagonizes the proliferative action of EGF, inhibits tyrosine phosphorylation of EGF receptor induced by EGF and significantly reduces the number of EGF binding sites, without altering the stimulation of c-fos expression induced by EGF. For the "in vivo" experiments, male nude mice were s.c. injected in the flank with DU 145 cells and treated for 14 days with LHRH-A (100 micrograms/days). At the end of the treatment, the concentration of EGF receptors on membrane preparations as well as on tumor volume were found to be significantly lower in LHRH-A treated animals than in control mice. The mitotic index and the expression of the proliferation-associated antigen Ki67 were found similar in control as well as in treated animals. In addition no modification of apoptotic index (expression of p53) was observed. These data suggest that LHRH agonists may inhibit the proliferation of the tumor cells by interfering with the stimulatory actions of EGF.

Topics: Animals; Antineoplastic Agents, Hormonal; Cell Division; Epidermal Growth Factor; ErbB Receptors; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Mice; Mice, Nude; Phosphorylation; Prostatic Neoplasms; Proto-Oncogene Mas; Tumor Cells, Cultured

Topics: Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Humans; Male; Patient Selection; Prostatic Neoplasms; Research Design

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Goserelin; Humans; Male; Outcome Assessment, Health Care; Prostatic Neoplasms; Research Design

The aim of this study was to investigate the effect of goserelin-acetat (Zoladex) on testosterone suppression, to compare achieved suppression with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of adiol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biological treatment effects. Fifteen patients were treated by Zoladex in one dose every 28 days, and followed-up for 12 months. All patients had several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase (ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing hormone (LH), foliculostimulating hormone (FSH), ALP and AP were also measured before every cycle. For evaluation of the life quality Rotterdam Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and AP. Testosterone and adiol displayed mainly inverse trends during treatment. The complete testosterone suppression was never achieved. It seems that Zoladex has quite different influence on LH and FSH, as levels of those hormones have shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of dopamine in hypothalamus which inhibits releasing of its hormones. By inhibition of corticotropic releasing factor and ACTH, and by its influence on adrenal gland, we could explain drop of adiol levels in the first months of administration of LHRH agonists. Testosterone increase and adiol drop in the first months, and adiol increase following testosterone level drop in the fourth to eight month, may be explained by negative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and consequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved for about 30% in psychological and functional domains. There were no significant changes on physical subscale, during treatment. It seems that the obtained positive psychological treatment effect is not only a consequence of pain decrease, but it could be the result o

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Alkaline Phosphatase; Androstenediol; Antineoplastic Agents, Hormonal; Bone Neoplasms; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Testosterone

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 second generation temporary stent (ProstaCoil*) was inserted into the prostatic urethra of patients with obstruction due to prostate cancer to allow spontaneous voiding during hormonal therapy given to decrease the size of the prostatic mass.. The stent was inserted under fluoroscopic guidance using topical anesthesia in 27 patients (mean age 77 years) who presented with urinary retention due to advanced carcinoma of the prostate. All patients underwent operative or nonoperative hormonal therapy shortly after insertion of the stent.. Followup of our patients was 3 to 48 months after stent removal and 15 void spontaneously. In 6 patients the stent was removed 9 to 19 months after insertion due to slow regression of the prostatic mass. Two of these patients required transurethral resection of the prostate and in 3 a new stent was inserted because of recurrent obstruction. two recently treated patients await stent removal and 3 died before removal of the stent. During followup no patient had urinary infection, either with the stent indwelling or after its removal.. Temporary internal stenting of the prostate should be the treatment of choice for relieving obstruction during hormonal therapy given for prostate cancer.

Topics: Aged; Antineoplastic Agents, Hormonal; Catheters, Indwelling; Equipment Design; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Stents; Time Factors; Urethra; Urinary Bladder Neck Obstruction; Urinary Catheterization; Urinary Retention

To examine the frequency and severity of toxicity associated with flutamide inpatients treated with total androgen suppression before and during pelvic radiation therapy (RT) for prostate cancer.. Sixty-five patients with T2b-T4 prostate cancer received flutamide and goserelin acetate for 4 months, with RT beginning at the 3rd month. Treatment records including liver function test (LFT) results at baseline and during treatment were reviewed and toxicities noted.. In 30 (46%) of 65 patients, flutamide was discontinued prematurely. Primary reasons included elevation in LFT levels (n=14); gastro-intestinal toxicity (n=9); decreased hemoglobin level (n=2); patient refusal (n=2); and arthralgia, rash, and malaise (n=1 each). Hepatotoxicity generally was manifest as asymptomatic transaminase level elevation. Grade 3-4 hepatotoxicity was noted in four of 65 patients. Mean aspartase aminotransferase increased from 23 (baseline) to 67 U/L (during flutamide treatment) (P<.02); mean alanine aminotransferase level increased from 26 (baseline) to 94 U/L (during flutamide treatment) (P<.005).. Flutamide toxicity was common. LFTs should be monitored during flutamide therapy. The role of flutamide in this treatment regimen may need to be reevaluated.

Topics: Aged; Alanine Transaminase; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents, Hormonal; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Clinical Enzyme Tests; Cohort Studies; Combined Modality Therapy; Flutamide; Gastrointestinal Diseases; Goserelin; Humans; Liver Function Tests; Male; Prospective Studies; Prostatic Neoplasms; Radiotherapy Dosage

No clear relation between lipoprotein(a) [Lp(a)] and endogenous gonadal hormones has been demonstrated. In this study, we compared the effects on Lp(a) of pharmacological castration in 50 patients with prostate cancer who were undergoing therapy with a gonadotropin-releasing hormone agonist (goserelin), with effects on 58 age-matched controls. We also studied 16 untreated patients under baseline conditions and after 3 months of therapy with goserelin alone or combined with an antiandrogen (flutamide). Neither cross-sectional nor prospective studies showed any significant effects of therapy on Lp(a). However, cluster analysis identified a subgroup of patients showing slight but significant increases in Lp(a) concentrations, as well as greater declines of testosterone and estradiol, suggesting that androgen, like estrogen, can exert some slight, though not easily detectable, influence on Lp(a).

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Androgens; Apolipoprotein A-I; Body Mass Index; Cholesterol; Cholesterol, HDL; Estradiol; Flutamide; Goserelin; Humans; Lipids; Lipoprotein(a); Male; Middle Aged; Prostatic Neoplasms; Testosterone; Triglycerides

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Clinical Trials as Topic; Combined Modality Therapy; Diethylstilbestrol; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms

Topics: Adaptation, Psychological; Antineoplastic Agents, Hormonal; Empathy; Goserelin; Humans; Male; Nurse-Patient Relations; Prostatic Neoplasms; Self Concept

The study entered sixty patients with advanced carcinoma of the prostate that were treated and followed-up by the authors. The median age was 70.3 years (range 58-83 years). In all patients a prostatic carcinoma has been morphologically proven. Orchiectomy was performed in 27 of them. Conservative treatment with Zoladex-monotherapy was applied in 21 patients and a combination of orchiectomy plus Zoladex-in 12 of the remaining. All patients were followed-up for the period of 3 months. Subjective and objective parameters were evaluated at 2, 4, 8 and 12 weeks during the treatment. Positive response to treatment was reported in 76% of the patients from the group of orchiectomy alone, 72% among the patients in the group of Zoladex depot and up to 80% in patients treated with orchiectomy plus Zoladex. The average time to achieve positive response was stated to be seven weeks for orchiectomy and Zoladex as a monotherapy and six weeks for the combination therapy.

Topics: Aged; Antineoplastic Agents, Hormonal; Chi-Square Distribution; Combined Modality Therapy; Drug Evaluation; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Remission Induction; Time Factors

Preirradiation hormonal cytoreduction of prostate cancer has been proven to reduce exposure of normal structures by decreasing the size of the target volume. Dose-volume histogram (DVH) analysis, however, does not always appear to demonstrate a strong positive benefit with the use of neoadjuvant hormone therapy. This study analyzes various other factors influencing dose to normal organs, which may determine the success or failure of neoadjuvant hormonal therapy in achieving its goals.. Patients with bulky clinical Stage C adenocarcinoma of the prostate were given 3 months of hormone treatment consisting of oral Flutamide and monthly Zoladex injections prior to irradiation. Computerized tomography (CT) scans of the pelvis were obtained both prior to and following hormonal treatment. Treatment plans were generated by three-dimensional (3D) conformal treatment planning. The change in the volume of the prostate was assessed along with the percentage of prescribed dose delivered to the rectum and bladder. Various factors such as prostate size, bladder/rectum size, and organ shape were studied. Both dose-volume histograms (DVH) and dose-surface area histograms (DSH) were used for analysis.. Six of seven patients had reduction in the size of their prostates. The mean volumes of the prostate before and after hormonal manipulation were 129.1 +/- 32.9 standard deviation (SD) cm3 and 73.0 +/- 29.5 SD cm3, respectively (p = 0.0059). The volume of rectum receiving 80% of the prescribed dose was reduced in five of seven patients from a mean of 83.2 to 59.9 cm3 (p = 0.045). The volume of bladder receiving 80% of the prescribed dose was also reduced in five out of seven patients from a mean of 74.5 to 40.2 cm3 (p = 0.098). Correlation between the size of the prostate and volume of rectum and bladder treated was not always consistent: greater reduction in prostate size did not necessarily result in large decreases in dose to bladder or rectum. The total size of the bladder and rectum were found to be important factors in normal tissue radiation exposure; the benefits of hormone therapy may be lost if the bladder and rectum are allowed to decrease in size. Also, the bladder may be prone to sagging into the pelvis of some patients following hormone therapy, resulting in a less optimal therapeutic ratio.. Reduction in prostate size by neoadjuvant hormonal manipulation does decrease the amount of normal tissue irradiated in most patients. However, the correlation between the reduction in prostate size and amount of rectum or bladder treated is not linear if other variables are not controlled. Factors such as the shape of the organs, as well as the distensible nature of the bladder and rectum, play major roles in dose to normal tissues. These facts may mask the benefits of cytoreduction and could be obstacles in realizing consistent benefits from preirradiation hormonal treatment in the clinical setting if they are ignored.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Flutamide; Goserelin; Humans; Male; Prostate; Prostatic Neoplasms; Radiotherapy Dosage; Rectum; Retrospective Studies; Urinary Bladder

Topics: Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Controlled Clinical Trials as Topic; Flutamide; Goserelin; Humans; Leuprolide; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds

To analyse the prognostic significance of pre- and post-treatment serum prostate-specific antigen (PSA) levels, together with a variety of other factors, in a multivariable analysis of survival in men with stage D2 prostate cancer.. Cox's proportional hazards model was used to compare survival in 134 men with stage D2 metastatic prostate cancer followed prospectively over a 4 year period, using both univariable and multivariable models. The influence of the following factors on survival was analysed: pre- and post-treatment PSA (both absolute and percentage values), age, treatment, testosterone, pre- and post-treatment alkaline phosphatase (absolute and percentage values), acid phosphatase, haemoglobin, symptom score and performance status and extent of disease on bone scan.. Pre-treatment PSA levels did not significantly influence survival. Similarly, a low absolute post-treatment PSA level at 3 months after the start of treatment conferred no survival advantage relative to patients with a high PSA level at this time. A post-treatment percentage PSA of < 10% at 2, 3 and 6 months after commencement of treatment was associated with prolonged survival. Low pre-treatment alkaline phosphatase (less than the upper limit of normal) and high pre-treatment testosterone levels (> or = 10 nmol/L) were similarly associated with prolonged survival.. The strong influence of post-treatment percentage PSA on survival in patients with stage D2 prostate cancer suggests that the percentage change in bulk of metastatic deposits is more important in determining survival than the absolute volume of tumour. Pre-treatment alkaline phosphatase seems to be a better indicator of tumour activity than pre-treatment PSA. These findings have important implications for the design and analysis of clinical trials of new therapies in men with stage D2 prostate cancer and for the future selection of alternative treatments for patients with this stage of the disease.

Topics: Aged; Cyproterone Acetate; Goserelin; Humans; Male; Middle Aged; Multivariate Analysis; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate

The usefulness of estramustine phosphate (ECT) for preventing flare-up in goserelin acetate depot therapy for advanced prostate cancer was studied. Pretreatment with ECT 560 mg daily for 3 weeks almost completely prevented the rise in testosterone level seen in goserelin acetate depot therapy and no signs or symptoms of tumor flare were observed. Long-term ECT completely blocked the rise in luteinizing hormone and testosterone level, but ECT at this dosage was likely to cause complications. The administration of ECT 560 mg daily for 3 weeks prior to goserelin acetate depot therapy was considered sufficient to prevent tumor flare, and its effect was considered to be more marked than that of short-term treatment with antiandrogens.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Carcinoma; Disease Progression; Drug Therapy, Combination; Estramustine; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Topics: Aged; Aged, 80 and over; Goserelin; Humans; Male; Pituitary Apoplexy; Prostatic Neoplasms

Eighty-two patients with stage T3 carcinoma of the prostate were treated for 3 months prior to radical retropubic prostatectomy with a luteinizing-hormone-releasing hormone analogue and an antiandrogen. Based on digital rectal examination (DRE), reduction of prostate and tumor size was noted in all cases. Ultrasound demonstrated a decrease in prostatic volume between 0 and 62.5% (median 32%). Prostate-specific antigen levels (PSA, Hybritech) decreased substantially (mean PSA of 29.5 ng/ml before to a mean PSA of 1.3 ng/ml after hormonal treatment). Pathologically, only 15 patients (18.3%) had organ-confined disease (stage pT2), 44 (53.7%) had stage pT3 tumors and 22 (26.8%) had positive lymph nodes. In 1 surgical specimen (1.2%), no residual tumor was identified. In 5 patients with nodal metastasis and 13 patients with seminal vesicle invasion, PSA levels after pretreatment were below 0.5 ng/ml. Compared to the preoperative needle biopsy, a decrease in the histological grade was found in only 7 tumors, while an increase was noted in 26. DRE, ultrasound and PSA suggest a downstaging of stage T3 prostate cancer after 3 months of maximum androgen deprivation. This cannot be confirmed pathologically. Prospective studies with this treatment regimen should concentrate on a possible benefit concerning local and distant cancer control and survival.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms

Seventy patients with clinical stage C carcinoma of the prostate were treated for 3 months with the gonadotropin-releasing hormone analog, goserelin acetate (Zoladex; Zeneca Pharmaceuticals, Macclesfield, UK) plus an antiandrogen (flutamide). Based on digital rectal examination (DRE), reductions of the size of the prostate and the tumor were noted in 91.4% of patients. Ultrasound demonstrated a decrease in prostatic volume between 0% and 62.5% (median 31%). Prostate-specific antigen (PSA) levels (Hybritech) decreased substantially (mean PSA of 31.3 ng/ml before, to a mean PSA of 1.4 ng/ml after hormonal treatment). A total of 64 patients subsequently underwent radical retropubic prostatectomy. Pathologically, only 9 patients (14.1%) had organ-confined disease (stage B), 34 (53.1%) had stage C tumors, and 21 (32.8%) had positive lymph nodes (stage D1). In 5 patients with nodal metastasis and 7 patients with seminal vesicle invasion, PSA levels after pretreatment were below 0.5 ng/ml. Maximal androgen blockade for a period of 3 months in clinical stage C prostate cancer induces a notable reduction in prostate size ("downsizing"). A "downstaging" effect, as suggested by DRE, ultrasound, and PSA, was not observed. Prospective studies with this treatment regimen should concentrate on a possible benefit concerning local and distant cancer control and survival.

Topics: Chemotherapy, Adjuvant; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Treatment Outcome

The treatment of locally advanced prostatic cancer is controversial, as there are several possible treatment options. The aims of temporary androgen deprivation prior to radical prostatectomy are to achieve downgrading and downstaging of the tumor, an increase in local control, a decrease in morbidity and operative sequelae, a decrease in the time to progression, and an improvement in survival. A retrospective study has been carried out on 100 patients who underwent radical prostatectomy between 1988 and 1992. Forty patients received androgen deprivation therapy followed by prostatectomy, while the remaining 60 acted as controls, undergoing prostatectomy alone. Treated patients had a 40-50% reduction in prostate volume after 3 months, facilitating dissection of the prostate, reducing intraoperative blood loss, and reducing operation time. Of these 40 treated patients, one third showed clinical downstaging; one patient staged initially as T2/B was downstaged to PT0. The proportion of patients with positive surgical margins was 32% in the group treated preoperatively, compared with 57% in untreated patients. Treated patients also recovered full continence more rapidly after the operation than patients who underwent prostatectomy alone. After androgen blockade, serum PSA levels returned to normal (< 4 ng/ml) in 37 of the 40 patients. Of these patients, 22 had undetectable serum PSA levels (< 0.25 ng/ml), showing a definite reduction in tumor activity. PSA levels after 3 months of neoadjuvant hormonal treatment might play a useful predictive role in selecting patients before radical prostatectomy, since 86% with undetectable PSA had tumors confined to the gland (T2/B2), while patients who still had PSA > 4 ng/ml all had stage T3-T4 tumors. Although downstaging was confirmed pathologically in only 13% of patients, this is of significance when the total number of patients with locally advanced prostate cancer is considered and, therefore, may have implications for survival in the future. Prospective randomized studies should provide conclusive information on the potential benefit of this approach.

Topics: Aged; Chemotherapy, Adjuvant; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Retrospective Studies

The dynamics of hormonal levels and tumor markers after the first administration of long-acting luteinizing hormone-releasing hormone (LH-RH) analogue were evaluated in patients with prostate cancer. Eight patients with histopathologically proved prostate cancer who were previously untreated were studied. The surge in plasma testosterone was recognized in 7 patients after the first administration of a long-acting LH-RH analogue, and reached the highest level after the 3rd day in 6 patients and 14th day in 1 patient. The onset of flare-up reaction due to a transient increase in plasma testosterone was recognized in 3 patients, whose clinical symptoms and signs were increased bone pain in 2 patients and acute urinary retention in 1 patient. An abnormal level of serum prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) was observed in 7 of the 8 patients before treatment. The serum PAP and PSA levels slightly increased after treatment in 4 and 3 patients, respectively. These findings suggest that the combination of estrogen or antiandrogen would allow a safer use of long-acting LH-RH analogue to prevent the risk of a flare-up reaction associated with the first administration of long-acting LH-RH analogue.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Biomarkers, Tumor; Delayed-Action Preparations; Gonadotropins; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Combined Modality Therapy; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Palliative Care; Prostatectomy; Prostatic Neoplasms; Quality of Life

Topics: Chemotherapy, Adjuvant; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms

To investigate the effect of upper tract decompression on the prognosis of uraemia secondary to bilateral ureteric obstruction in prostate cancer, with particular reference to the hormone dependency of the tumour.. Prospectively collected data, over the period 1978-1993, were selected from the departmental database and from hospital case code data. Inclusion criteria were: blood urea > or = 15 mM, radiological evidence of bilateral ureteric obstruction, a histological diagnosis of prostate cancer, and the exclusion of out-flow tract obstruction. Of the 820 patients recorded in the departmental database, 27 (3.3%) fulfilled the criteria. Thirty-six patients were identified in total. Statistical analysis was by the Mann-Whitney non-parametric test.. Of the 36 patients with bilateral ureteric obstruction and renal failure, in those in whom androgen depletion had been undertaken after ureteric obstruction (i.e. androgen depletion was a treatment option), the mean survival was 646 days (n = 12, SD = 786). Among these patients upper tract decompression improved survival and reduced the amount of time patients spent in hospital. In those in whom androgen depletion had been carried out before obstruction (i.e. the tumour had escaped from hormonal control), survival was significantly worse (80 days, n = 24, SD = 86.8, P < 0.01). In this group the use of decompression improved survival little. Percutaneous nephrostomy was the commonest means of decompression (nephrostomy, 9; stent, 5; ureteroneocystostomy, 2).. In patients for whom hormonal therapy remains an option, upper tract decompression offers a worthwhile improvement in terms of increased survival and reduced in-patient time. However, if ureteric obstruction is diagnosed after hormone manipulation has been used, upper tract decompression has little effect on survival and should only be used in exceptional circumstances.

Topics: Cyproterone Acetate; Cystostomy; Goserelin; Humans; Kidney Failure, Chronic; Length of Stay; Male; Orchiectomy; Prognosis; Prospective Studies; Prostatic Neoplasms; Stents; Ureteral Obstruction; Ureterostomy

Topics: Adult; Combined Modality Therapy; Flutamide; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Survival Rate

The therapeutic options for the treatment of androgen-independent prostatic cancers are rather limited; this is mainly because our understanding of the local mechanisms involved in the control of androgen-independent proliferation of the tumor is still very poor. The present experiments have been performed to verify whether luteinizing hormone-releasing hormone (LHRH) agonists may possess a direct effect on the growth of the human androgen-independent prostate cancer cells DU 145 and whether a LHRH growth regulatory system may be present in these cells. The data have shown that two potent LHRH agonists (Zoladex and Buserelin) exert a significant and dose-dependent antiproliferative action on DU 145 cells, after 4 days of treatment. The inhibitory action of Zoladex and Buserelin is completely counteracted by the simultaneous treatment of the cells with a potent LHRH antagonist, suggesting that the action of the LHRH agonists may be mediated by specific receptors. This hypothesis has been confirmed by the demonstration that low-affinity binding sites for 125I-Buserelin are present on DU 145 cell membranes, particularly when cells are cultured in serum-free conditions. By using the reverse transcription-polymerase chain reaction technique, in the presence of a pair of specific oligonucleotide primers complementary to the human LHRH complementary DNA, it has been demonstrated that a mRNA for LHRH is expressed in DU 145 cells. Taken together, these data seem to indicate that an autocrine/paracrine LHRH (or LHRH-like) loop is present in androgen-independent prostate cancer cells, and may participate in the regulation of tumor cell growth. To verify this hypothesis, DU 145 cells have been cultured in serum-free conditions, and treated with a LHRH antagonist for 4 days. The treatment resulted in a significant increase of cell proliferation, suggesting an inhibitory role for the LHRH system in the local regulation of cell growth. In conclusion, these data demonstrate that: (a) LHRH agonists exert a specific antiproliferative action on the human androgen-independent DU 145 cells; (b) an autocrine/paracrine LHRH (or LHRH-like) loop, which seems to be inhibitory on cell proliferation, is expressed in DU 145 cells.

Topics: Animals; Buserelin; Cell Division; Drug Screening Assays, Antitumor; Gonadotropin-Releasing Hormone; Goserelin; Male; Prostatic Neoplasms; Rats; Rats, Sprague-Dawley; Receptors, LHRH; Tumor Cells, Cultured

Topics: Adenocarcinoma; Aged; Goserelin; Humans; Male; Middle Aged; Osteoporosis; Prostatic Neoplasms

A total of 77 men with prostatic carcinoma treated with orchiectomy or a gonadotropin releasing hormone analogue before September 1987 underwent evaluation by a questionnaire regarding vasomotor symptoms. Answers were received from 84% of the patients. Of 63 patients 43 (68%) reported hot flushes during treatment, while 30 (48%) still had flushes 5 years after treatment. Of the latter 30 patients 28 (median 7.6 years after treatment) had vasomotor symptoms at the time of the study. Only 13 of 43 men with vasomotor symptoms after the start of treatment had relief 5 years later. At the time of the study 13 of 30 patients (more than 40%) still had flushes 8 years after castration. Most men reported that the flushes presently had the same frequency and duration as when they started therapy. Contrary to the general belief that the symptoms disappear with time, our study highlighted a long persistence of hot flushes after castration.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Climacteric; Goserelin; Humans; Male; Orchiectomy; Postoperative Complications; Prevalence; Prostatic Neoplasms; Retrospective Studies; Severity of Illness Index; Time Factors

Topics: Drug Implants; Endometriosis; Female; Goserelin; Humans; Injections, Subcutaneous; Male; Prostatic Neoplasms; Uterine Diseases

Since postcastration progression of tumors to an androgen-independent state appears to be linked to the cessation of androgen-induced differentiation of tumorigenic stem cells, the authors hypothesized that the replacement of androgens at the end of a period of apoptotic regression might result in the regeneration of differentiated tumor cells with further apoptotic potential.. To determine the effect of intermittent exposure of androgens on the androgen-dependent Shionogi carcinoma, the tumor was transplanted into a succession of male mice, each of which was castrated when the estimated tumor weight became about 3 g. After the tumor had regressed to 30% of the original weight, it was transplanted into the next noncastrated male. This cycle of transplantation and castration-induced apoptosis was repeated successfully four times before growth became androgen-independent during the fifth cycle. In four of Stage C and three of Stage D patients with prostate cancer, androgen withdrawal was initiated with cyproterone acetate (100 mg/d) and diethylstilbestrol (0.1 mg/d) and then maintained with cyproterone acetate in combination with the luteinizing hormone-releasing hormone agonist, goserelin acetate (3.6 mg/month). After 6 or more months of suppression of serum prostate-specific antigen (PSA) into the normal range, treatment was interrupted for 2 to 11 months. After recovery of testicular function, androgen-withdrawal therapy was resumed when serum PSA increased to a level of about 20 micrograms/l. This cycle was repeated sequentially to a total of two to four times over treatment periods of 21 to 47 months with no loss of androgen dependence.. These results demonstrate that intermittent androgen suppression can be used to induce multiple apoptotic regressions of a tumor; they also suggest that the cyclic effects of such treatment on prostate cancer can be followed by the sequential measurement of serum PSA levels.

Topics: Adenocarcinoma; Aged; Animals; Apoptosis; Cyproterone Acetate; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Mammary Neoplasms, Experimental; Mice; Middle Aged; Neoplasm Staging; Neoplasm Transplantation; Neoplasms, Hormone-Dependent; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

The main goal of hormonotherapy in management of locally advanced or metastatic prostate cancer is the control over the progression of the neoplastic disease rather than a possible benefit to the primary lesion. Nevertheless during hormonal treatment an evident decrease of prostatic volume can often be noted even though its clinical meaning has rarely been investigated. In order to evaluate a possible correlation between local modifications and prognosis, a retrospective analysis of a group of patients on hormonotherapy was performed. From March 1987 to March 1991, 98 patients with clinical stage C and D2 prostate cancer were treated. Fifty two of them were considered eligible for assessing local response because they had had neither surgery nor radiotherapy over the prostate; moreover their pre-treatment prostatic volume, as assessed by US scan, exceeded 22 ml. Out of these patients 24 were given Goserelin every 4 weeks and the remaining 28 added Flutamide at the dose of 750 mg per day. The prostatic volume was assessed quarterly and considered as response if decreased more than 35% of pretreatment value or as progression if increased over 25% of immediately previous value. In both cases the result needed to be confirmed three months later, but it was registered when first observed. After a mean follow-up of 32.4 +/- 18.7 months a local response occurred in 44 patients (84.6%) during a period ranging 3 to 18 months. Eight patients did not show a prostatic volume decrease and 4 suffered of local progression. In these latter cases the local progression coincided with distant progression.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Actuarial Analysis; Combined Modality Therapy; Drug Therapy, Combination; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Organ Size; Prognosis; Prostate; Prostatectomy; Prostatic Neoplasms; Retrospective Studies; Survival Analysis; Testosterone; Treatment Outcome

Luteinizing hormone-releasing hormone (LHRH) agonist therapy is commonly used as a form of hormonal ablative therapy in patients with advanced prostate cancer. It is important to administer LHRH agonist every four weeks. Any delay of more than two weeks is associated with the risk of disease flare. A retrospective review of two groups of patients were compared. Twenty-five patients treated at the Veterans Administration Medical Center, Louisville, Kentucky, showed that 44 percent missed one or more injections and 24 percent had a delay of more than two weeks after the scheduled time for another injection. Twenty-three patients were treated by a private practice group in Louisville, Kentucky. There were no problems with compliance. An office nurse kept a separate register for patients receiving LHRH agonist therapy and their appointments. For LHRH therapy to be effective, we believe that the level of compliance one could expect from an individual should be determined before instituting LHRH agonist therapy. If good compliance is not assured, alternative forms of hormone ablative therapy may be preferable for patients with advanced prostate cancer.

Topics: Aged; Aged, 80 and over; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Patient Acceptance of Health Care; Prostatic Neoplasms; Receptors, LHRH; Retrospective Studies

A 65-year-old man with advanced prostate cancer was treated with a luteinizing hormone-releasing hormone (LH-RH) analogue. Four days after the initial injection of 3.6 mg of goserelin acetate, severe dyspnea developed due to worsening pleuritis carcinomatosa, which was considered as a flare-up. Chest drainage was required to save his life. Therefore, we emphasize the importance of treatment to prevent tumor flare during LH-RH analogue therapy.

Topics: Adenocarcinoma; Aged; Drainage; Goserelin; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Pleural Effusion, Malignant; Prostatic Neoplasms

Eighty-two patients with advanced prostatic carcinoma were treated with a long-acting luteinizing hormone releasing hormone (LHRH) agonist (Zoladex depot, Zeneca Pharmaceuticals, England). The outcome of the treatment was monitored on the basis of the following prognostic factors: local stage, number of bone metastases, histological differentiation grade and prostate-specific acid phosphatase (PAP), alkaline phosphatase (AF) and testosterone levels. The patients were followed-up until disease progression or until death. The mean weight of the prostate decreased from 48.1 g to 17.4 g (P < 0.00001) during the first year of treatment. Statistically there was a significant difference in regard to appearance of progression between different clinical stages (P < 0.00001). The prognosis was poorest in patients with more than 10 metastases at the primary stage. If the PAP level was initially higher (over 20 micrograms/L), the prognosis was very poor. Statistically there was a significant difference between the high PAP level and the slightly elevated or normal PAP (P < 0.02 and P < 0.005, respectively). Alkaline phosphatase (AF) appeared to be a good prognostic factor. The prognosis was particularly poor, if the AF level exceeded 1000 U/L (P < 0.00001 and P < 0.05, compared with normal AP and slightly elevated AP level, respectively). Surprisingly, a high pre-treatment testosterone level worsened the prognosis during the LHRH agonist treatment (P < 0.01, compared to patients with normal testosterone level). This is a new finding and controversial to the findings reported before.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Follow-Up Studies; Goserelin; Humans; Life Tables; Male; Neoplasm Staging; Prognosis; Prostate; Prostatic Neoplasms; Testosterone; Time Factors; Treatment Outcome

The study was carried out in order to investigate the possibility of tumor reduction in prostate cancer patients. As a reduction of the primary tumor was observed with hormonal treatment and complete response of soft tissue tumor markers with Mitomycin C, this combined treatment was given in seven patients to evaluate if it was able to down-stage those cases which were thought to be incurable (T3N1-2M0/T4N0-2M0). Although the clinical evaluation suggested a significant down-staging, the explorative lymphadenectomy was unable to confirm this. The proposed treatment is able to reduce the tumor bulk significantly of the primary cancer as well as of its metastases; progression during the treatment was not seen.

Topics: Aged; Combined Modality Therapy; Drug Therapy, Combination; Goserelin; Humans; Lymph Node Excision; Male; Middle Aged; Mitomycin; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms

To compare the costs of the various options presently available in Australia for treatment of advanced prostatic carcinoma by androgen deprivation.. Forty patients underwent a bilateral orchidectomy for prostatic carcinoma during the 1990/91 financial year at the Princess Alexandra Hospital, Brisbane. The Yale Cost Model, as adapted for use in Australian case-mix projects, was used to derive a diagnosis related group (DRG) cost for this procedure. This was compared with the projected cost that would be incurred in treating patients with the various medical alternatives. To enable comparison, expenses were calculated assuming a mean duration of survival of two years.. The average cost of a bilateral orchidectomy was $2869. This compared to $11,253 for goserelin and $12,329 for cyproterone acetate when used alone in treating a single patient. Flutamide is presently only approved for combination therapy with a luteinising hormone-releasing hormone agonist, and when used with goserelin an average cost of $16,148 per patient was projected.. Bilateral orchidectomy is clearly the cheapest means of hormone manipulation for prostatic carcinoma. Unless the costs of alternative therapies are drastically reduced in Australia, their use is difficult to justify in other than exceptional circumstances. We believe their use should be restricted presently to patients who would otherwise require a bilateral orchidectomy and have an anticipated survival of less than six months.

Topics: Combined Modality Therapy; Cyproterone Acetate; Diagnosis-Related Groups; Drug Costs; Drug Therapy, Combination; Flutamide; Goserelin; Health Care Costs; Humans; Male; Orchiectomy; Prostatic Neoplasms; Queensland

Fasting serum lipoproteins were measured in patients with carcinoma of the prostate. Twelve patients were on no hormonal treatment (Group 1). Fifteen were on cyproterone acetate (Group 3), 17 were on the long-acting LHRH analogue Zoladex (Group 4) and 11 on a combination of cyproterone acetate and Zoladex (group 5). In addition, 27 patients with benign urological disease were taken as controls (Group 2). In both groups in which cyproterone acetate was part of the treatment the total high density lipoprotein cholesterol levels were significantly lower than in the other groups. Patients on cyproterone acetate alone had significantly higher levels of very low density lipoprotein (VLDL) triglyceride levels than those not on cyproterone acetate. These results confirm changes in serum lipoprotein levels in patients taking cyproterone acetate and these changes may have potential adverse effects if the treatment is prolonged.

Topics: Cholesterol; Cyproterone Acetate; Drug Therapy, Combination; Goserelin; Humans; Lipoproteins; Male; Prostatic Neoplasms; Triglycerides

To determine the effects of clonidine, a centrally acting adrenergic agonist, in abating symptoms of hot flashes in men receiving either leuprolide or goserelin for prostate cancer.. Patients were administered transdermal or oral clonidine 0.1-0.2 mg/d. Dosages were increased in increments of 0.1-0.3 mg/d every two to four weeks if symptoms persisted or until adverse effects developed.. Medical oncology clinic at the University of Illinois and the hypertension clinic at the Veterans Affairs West Side Medical Center.. Consenting male patients were eligible for the study if they were receiving leuprolide or goserelin for prostate cancer and were experiencing hot flashes. Exclusion criteria included diastolic blood pressure of 75 mm Hg or below or a history of adverse reactions to clonidine.. Effectiveness of clonidine was determined by questioning patients about frequency, severity, and duration of hot flashes at baseline and at two- to four-week intervals.. All four patients receiving clonidine experienced a partial response within two weeks of starting treatment. No dose-dependent response was observed. Adverse effects were noted in one patient but did not result in discontinuation.. Our results document the first report of the use of clonidine to treat hot flashes secondary to leuprolide or goserelin therapy. Symptomatic improvement was noted in all four patients. Further evaluation of clonidine as well as other centrally acting adrenergic agonists is needed.

Topics: Climacteric; Clonidine; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Time Factors

Topics: Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms

Thirty-one patients with retention of urine and carcinoma of the prostate were treated with LHRH analogues as primary therapy rather than prostatectomy; 21 patients voided without the need for surgical intervention. Patients presenting in acute retention of urine voided more readily than those presenting in chronic retention, with only 20% requiring surgery. This approach to treatment is safe, efficacious and cost effective.

Topics: Acute Disease; Aged; Chronic Disease; Goserelin; Humans; Male; Prostate; Prostatic Neoplasms; Urinary Retention; Urination

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease Progression; Flutamide; Goserelin; Humans; Male; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Adenocarcinoma; Aged; Drug Resistance; Flutamide; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Inasmuch as treatments for advanced prostate cancer may have identical clinical outcomes but very different meanings to patients, we sought to compare the impact of surgical and medical castration (orchiectomy versus injected goserelin acetate Zoladex) on quality of life and psychosocial status. A total of 147 men with Stage D prostate cancer participated in the study: 115 selected treatment with goserelin acetate, and 32 chose orchiectomy. Quality of life, as measured by the Functional Living Index: Cancer (FLIC), improved at both the 3 and the 6 month follow-up in the goserelin acetate group (p = 0.0001), but did not change from baseline at 6 months in the orchiectomy group (p = 0.54). These findings were paralleled by improvement from baseline in psychosocial status, as measured by the Profile of Mood States (POMS), at 6 month follow-up (p = 0.01 in the goserelin acetate group versus p = 0.60 in the orchiectomy group). This investigation, which is among the first to evaluate patients' appraisals of their lives following treatment choices for advanced prostatic cancer, argues compellingly for including quality of life in assessments of therapy.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Demography; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Psychological Tests; Quality of Life; Sexual Behavior

Highly potent LH-releasing hormone (LHRH) agonists have been recently introduced in therapy for the treatment of the carcinoma of the prostate, an androgen-dependent pathology. These peptides are believed to act mainly by inhibiting the pituitary-testicular axis and, consequently, by reducing testosterone levels. The recent observation that binding sites for LHRH analogs are present on prostatic tumor tissue suggests that these drugs could also act directly on the tumor. To verify this hypothesis, the effects of two potent LHRH agonists [Zoladex (Z) and Buserelin (B)] have been studied on the proliferation of the human prostatic cancer cell line LNCaP (lymph node carcinoma of the prostate). LNCaP cells were treated for 9 days with different doses of either Z or B (concentrations from 10(-12)-10(-6) M). Both analogs significantly inhibited cell proliferation at doses between 10(-9)-10(-6) M. The antiproliferative action of the two LHRH agonists was shown to be dose dependent, with IC50 values of 0.82 and 1.79 nM for Z and B, respectively. A similar treatment with B was without any significant effect on the proliferation of a mouse embryo fibroblast cell line (Swiss 3T3), which was used as a nontumoral control. The inhibitory action of both LHRH agonists (10(-8) M) on LNCaP cell proliferation was completely antagonized by the simultaneous treatment of the cells with a potent LHRH antagonist (Nal-Arg-LHRH; 10(-8) M); when given alone at the dose selected, the antagonist did not affect cell growth. These results clearly suggest that the antiproliferative effect of LHRH agonists on LNCaP cells may be mediated by specific receptors. The presence of binding sites for [125I]B was consequently demonstrated on the membranes of LNCaP cells cultured in a medium containing charcoal-stripped fetal calf serum, i.e. in the absence of steroids. The affinity of these binding sites for the ligand was lower than that observed for the same receptors on rat pituitary membranes. To clarify the mechanism of the antiproliferative action of the LHRH agonists, the effects of both Z and B on the incorporation of [3H]thymidine and [14C]methionine into LNCaP cells were investigated. During a short incubation period (3 h), the two LHRH agonists rapidly inhibited [3H]thymidine incorporation into the cells. The same treatment did not affect the incorporation of [14C]methionine into proteins.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Antineoplastic Agents; Binding Sites; Buserelin; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Methionine; Prostatic Neoplasms; Receptors, LHRH; Thymidine; Tumor Cells, Cultured

The biochemical markers alkaline phosphatase (Alk P), prostatic acid phosphatase (PAP) and prostate-specific antigen (PSA) were measured 3-monthly in 61 patients with disseminated prostatic cancer who were treated with LHRH analogues. The decrease in Alk P and PSA during the first 6 months of treatment was significantly related to a better survival. In this follow-up study, only PSA was useful for monitoring prostatic cancer during hormonal treatment. Before it was visible on a bone scan, PSA gave an indication of tumor progression. PSA might permit omission of routine bone scanning. Consensus must be obtained about the cost-saving use of biochemical markers in the treatment of disseminated prostatic cancer. With the number of treatment options increasing, objective measures are of utmost importance. Biochemical markers can be used for prognosis and monitoring of the treatment of patients with disseminated prostatic cancer.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Buserelin; Follow-Up Studies; Goserelin; Humans; Male; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Time Factors

Changes in prostate-specific antigen (PSA) have been demonstrated to accurately assess response to initial hormone deprivation in metastatic prostate cancer patients. The role of PSA in monitoring response to second-line hormonal treatment has not been documented. In a group of 20 patients with an initial response to androgen deprivation and subsequent relapse, we monitored PSA levels before and after second-line therapy. Ten patients had a clinical response. Four had a more than 90 percent decrease in serum PSA compared with the level at initial progression. This clinical response was maintained for a mean of eighteen months. Six patients had a PSA decrease less than 90 percent; their clinical response was of a mean 5.5 months. Ten patients had no change or increase in PSA. Seven had no clinical response, and 3 responded for an average of four months. Although production of PSA might be under endocrine control, changes in PSA are useful for monitoring response to second-line hormonal therapy.

Topics: Androgen Antagonists; Anilides; Antigens, Neoplasm; Biomarkers, Tumor; Buserelin; Goserelin; Humans; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

The prognostic value of deoxyribonucleic acid (DNA) flow cytometry, cytological grading and the direct assay of prostate specific antigen (PSA) in the material of fine needle aspirates was studied in 67 consecutive patients with newly detected prostatic carcinoma. All patients were hormonally treated (castration in 27 and luteinizing hormone-releasing hormone agonist or parenteral estrogens in 40). The patients were followed for a minimum of 2 years. PSA was analyzed in the biopsy material by a direct radioimmunoassay and related to the total amount of DNA. In parallel biopsies DNA ploidy using flow cytometry and cytological grade were established. Patients with a geometric mean value of greater than or equal to 0.12 microgram. PSA/microgram. DNA had a progression rate of 7%, compared to 59% for those with less than 0.12 microgram. PSA/microgram. DNA. In Cox multivariate analysis cytology and tissue PSA content were the most important factors in expressing the difference for interval to progression in hormonally treated patients.

Topics: Antigens, Neoplasm; Biomarkers, Tumor; Biopsy, Needle; Buserelin; DNA, Neoplasm; Estrogens; Follow-Up Studies; Goserelin; Humans; Male; Multivariate Analysis; Orchiectomy; Ploidies; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms

The prognostic value was determined of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) measured before and after endocrine treatment in 57 patients with newly diagnosed Stage D2 prostatic cancer.. Therapy included orchiectomy or administration of luteinizing hormone releasing hormone analogues or an antiandrogen.. The absolute pretreatment PSA (elevated in 100% of patients) but not PAP (abnormal in 93%) predicted disease progression (P < 0.0011), i.e., a poor response to therapy. Fifty-three patients responded to androgen deprivation with a decrease in PSA level. This declined to normal at 3 and 6 months in 25% of patients. Forty-nine percent had a greater than 90% decrease in their PSA level. By 1 year, 58% of patients had progressive disease. Both the nadir PSA level and the percent decline from the pretreatment level at 3 and 6 months predicted the progression-free interval (P < 0.001). Patients with a 90% or greater decline in PSA had a prolonged progression-free survival. Serial PAP levels were similarly prognostic.. It was concluded that PSA was better than PAP in evaluating patients before and after androgen-deprivation therapy. The nadir level of both markers was an important tool to predict progression-free survival in patients with metastatic prostatic cancer.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Androgen Antagonists; Biomarkers, Tumor; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Time Factors

We have studied the prognostic significance of prostate-specific antigen (PSA), monitored monthly, in 24 patients with prostatic cancer (5 D1, 19 D2) on endocrine therapy. The pretreatment levels of PSA were high in all patients (mean value 41 ng/ml). It was found that PSA levels at the end of the first and sixth months of treatment were reliable prognostic indicators. At the first month evaluation PSA had decreased more than 50% from the initial values in the 16 patients with stable disease, while it had decreased less than 50% in those with progressing disease. At the end of 6 months, patients with stable disease had PSA levels within the normal range, while 8 of the patients who had progressing disease had levels higher than 10 ng/ml. Respectively 6 and 2 patients had also had increases in PSA levels at 3 and 6 months before scintigraphic demonstration of increased bone metastases.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Goserelin; Humans; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms

Topics: Antineoplastic Agents; Buserelin; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms

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

We report the effect on prostatic volume of the administration of the luteinising hormone-releasing hormone (LHRH) analogue goserelin in 22 patients with locally advanced carcinoma of the prostate; 20 achieved a significant reduction in volume, the median volume being 66 ml before treatment (range 40-130) and 30 ml after 17 weeks (range 13-47). If used before external beam radiotherapy (RT), volume reduction will permit smaller boost fields and thus potentially reduce adverse radiotherapy effects. In addition, reducing tumour volume before RT may lead to an increase in local control. We discuss the possible role of hormonal volume reduction in the management of prostatic cancer.

Topics: Buserelin; Combined Modality Therapy; Goserelin; Humans; Male; Prostatic Neoplasms

Topics: Combined Modality Therapy; Drug Implants; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms

A 78-year-old male was treated with goserelin (Zoladex) for 16 months for metastasizing prostate carcinoma. This therapy is clinically equivalent to orchidectomy, as the application of the luteinizing hormone-releasing hormone (LHRH)-analogue Zoladex causes suppression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by down-regulation of pituitary receptors. Consequently, testicular androgen production is inhibited and testosterone levels are decreased to castration levels. In the present case we found diffuse, partially nodular hyperplasia of growth hormone (GH) and adrenocorticotropin (ACTH) producing cells in the anterior pituitary gland at autopsy. As Zoladex reduces pituitary receptors for releasing hormones (RH), a globally increased hypothalamic secretion of RH might be responsible for the ACTH- and the GH-cell hyperplasia. We cannot exclude that Zoladex may cause not only adenomas in rat pituitary glands as reported previously, but also a (nodular) hyperplasia of the pituitary gland in man.

Topics: Adrenocorticotropic Hormone; Aged; Buserelin; Goserelin; Growth Hormone; Humans; Hyperplasia; Immunohistochemistry; Male; Neoplasm Metastasis; Orchiectomy; Pituitary Gland, Anterior; Prostatic Neoplasms

Serum testosterone and prostate-specific antigen (PSA) levels were measured in 3 patients with Stage D2 prostate cancer before and after discontinuation of the long-acting LHRH agonist, goserelin acetate (Zoladex). The patients had received goserelin acetate for ten, sixteen, and thirty months prior to discontinuing the drug because of progressive metastatic disease. In all 3 patients, PSA and testosterone levels increased after goserelin acetate was discontinued. In 2 patients the testosterone level reached normal levels. A bilateral orchiectomy was performed one hundred sixty, one hundred, and seven days, respectively, after the drug was discontinued. In all 3 cases PSA and testosterone levels were reduced following castration, although PSA levels again began to increase within two weeks of orchiectomy in 2 of the 3 patients. These findings suggest that suppression of testosterone by LHRH agonists is not permanent and if tumor progression occurs, maintaining hormone suppression may still be beneficial.

Topics: Aged; Antigens, Neoplasm; Buserelin; Combined Modality Therapy; Goserelin; Humans; Male; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

Sixty patients with advanced prostatic carcinoma were treated with monthly subcutaneous injections of a depot formulation of goserelin, a luteinizing hormone-releasing hormone (LHRH) analogue (Zoladex, ICI Pharma, Destelbergen, Belgium). All patients were regularly evaluated with measurements of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and prolactin (PRL) levels. In 15 patients among them who could be treated for more than 42 months, an LHRH stimulation test was performed at the end of each 28-day period and before the next administration of the depot formulation. A complete and maintained suppression of both T and LH levels was seen. FSH levels also decreased, but to a lesser extent than LH levels, and showed a small escape after reaching a minimum value after 1 month of therapy. The LHRH challenge after 42 months of therapy elicited no significant responses of LH and FSH levels. The PRL values showed a small decrease.

Topics: Aged; Buserelin; Follicle Stimulating Hormone; Gonadotropins; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Prolactin; Prostatic Neoplasms; Testosterone

Lymphangitic carcinomatosis of the lung is a late and often fatal manifestation of cancer. We describe a case of a biopsy-proved pulmonary lymphangitic carcinomatosis in an asymptomatic 61-year-old man. The pulmonary picture proved to be the initial sign of a prostatic cancer. Therapy with LH-RH analogues and antiandrogens achieved a complete clearance of lung involvement.

Topics: Buserelin; Carcinoma; Flutamide; Goserelin; Humans; Lung Neoplasms; Lymphangitis; Male; Middle Aged; Prostatic Neoplasms

Topics: Aged; Buserelin; Choice Behavior; Consumer Behavior; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms

Histomorphometric measurements of tumour-free bone have been undertaken in a closely matched group of patients with metastatic prostate cancer treated either by subcapsular orchidectomy (SCO) or luteinising hormone-releasing hormone (LHRH) agonists. Age, fasting morning urine hydroxyproline/creatinine ratios, alkaline and acid phosphatase levels and elapsed time after hormonal manipulation were similar in those receiving SCO (n = 8) as compared to LHRH therapy (n = 8). Results indicated that osteoid surface and mineralisation rate were significantly reduced in the SCO group (p less than 0.05); other indices were also lower in the SCO patients but failed to reach statistical significance. These changes, possibly due to increased adrenal cortical stimulation secondary to elevated gonadotrophin levels following orchidectomy suggest that medical castration by gonadotrophin inhibition may avoid unnecessary morbidity due to treatment-induced bone dysfunction.

Topics: Aged; Aged, 80 and over; Bone and Bones; Bone Density; Buserelin; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms

In 20 patients with locally advanced or metastatic prostate cancer, testicular tissue obtained by bilateral subcapsular orchidectomy was examined for steroid hormone content and morphological changes. Eight patients (group I) had not received previous treatment. Twelve patients had been treated with monthly subcutaneous doses of the depot luteinizing hormone-releasing hormone (LHRH) agonist D-ser (BUT)6 Azgly10-LHRH (ICI 118-630). Six patients (group II) had been treated for less than 6 months and 6 patients (group III) for more than 6 months. The longest duration of treatment with depot LHRH was 36 months. After 2 months of treatment (group II), maximum hormone suppression was achieved and remained unchanged even if treatment was continued for 3 years. The mean serum testosterone levels were decreased in group II (means = 0.586 mg/ml) and in group III (means = 0.575 mg/ml) and were found to be in the range of castration; a statistically significant reduction in luteinizing hormone (P less than 0.000001) and follicle-stimulating hormone (P less than 0.05) was observed in the treated patient groups. The content of the steroid hormones dihydroepiandrosterone sulfate (DHEA)-S, testosterone, androstenedione, oestradiol, progesterone and 17-alpha-hydroxyprogesterone/g testicular tissue was significantly lower in patients on LHRH agonists. The differences in concentration were particularly pronounced for DHEA-S, T and A. As in the case of serum concentrations, the testicular tissues showed no differences between groups II and III. In the treated groups a significant reduction in weight was seen, depending on the duration of therapy. Similarly, the structural changes visible by the aid of light and electron microscopes increased with the duration of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aged; Aged, 80 and over; Androgens; Antineoplastic Agents; Buserelin; Goserelin; Humans; Male; Prostatic Neoplasms; Testis; Time Factors

Since January 1989, we have carried out a prospective study about whether patients prefer orchidectomy or medical castration with luteinising hormone releasing hormone analogues for the treatment of prostatic cancer. When the preliminary results were presented, 40 Norwegian urologists were asked which treatment they would prefer if they had advanced cancer of the prostatic gland. Most patients and urologists (65-70%) favoured medical castration.

Topics: Adult; Aged; Aged, 80 and over; Attitude of Health Personnel; Buserelin; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms

Two patients with prostate carcinoma and bone metastases were treated with hormonal therapy. Radioimmune imaging of bone marrow performed with 99mTc-labeled antigranulocyte antibody BW 250/183 before treatment demonstrated absence of granulopoietic bone marrow in extensive regions of the central and proximal peripheral skeleton, indicating diffuse bone marrow invasion. Bone marrow scans performed after treatment demonstrated presence of granulopoietic bone marrow in these regions, indicating bone marrow regeneration. This finding was consistent with favorable response to treatment.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Bone Marrow; Bone Neoplasms; Buserelin; Flutamide; Goserelin; Humans; Male; Middle Aged; Organotechnetium Compounds; Prostatic Neoplasms; Radionuclide Imaging; Regeneration

Topics: Androgen Antagonists; Buserelin; Flutamide; Goserelin; Humans; Imidazoles; Imidazolidines; Leuprolide; Male; Orchiectomy; Prostatic Neoplasms

The role of prostate-specific antigen (PSA), a sensitive tumor marker for cancer of the prostate, has yet to be defined in patients treated with radiotherapy. To evaluate this, PSA and acid phosphatase (AP) were measured prospectively in 110 sequential patients who presented with locoregional carcinoma of the prostate and in whom radiotherapy was to be definitive treatment. Therapy was divided into the following treatment groups: external-beam radiotherapy alone (EBRT), EBRT with brachytherapy (EBRT + B), and hormone therapy either pre-EBRT or post-EBRT (EBRT + H). All patients have been followed for 1 to 17 months and a total of 521 posttreatment PSA determinations have been made. In 91 of 110 patients (83%) PSA was elevated pretreatment and correlated with clinical stage and subsequent relapse. There was no association with Gleason grade, assigned treatment group, or lymph node involvement. Acid phosphatase was elevated in only 31% of the patients initially and had no predictive value in subsequent failure. Nine patients have developed local and/or distant recurrence. None of the patients who failed had their PSA return to normal whereas 74 of 101 (73%) of the remainder have done so. Levels of PSA that do not return to normal during follow-up probably indicate active disease, often without evidence of clinical relapse. The authors conclude that PSA is a useful tumor marker for monitoring response to radiotherapy and may be a predictor of eventual failure thus identifying patients eligible for early intervention therapy as and when it becomes available.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Antigens, Neoplasm; Biomarkers, Tumor; Brachytherapy; Buserelin; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms

Serum prostate-specific antigen (PSA) levels were studied in the EORTC trial of zoladex plus flutamide versus orchidectomy in metastatic prostatic cancer. Forty-four of 60 patients had a decrease of PSA to less than or equal to 10 ng/ml at 3 to 6 months after treatment. The combination of a PSA less than 10 ng/ml after 3 to 6 months treatment and less than 15 spots on the bone scintigram at entry gave the highest probability of not having progressed by 24 months. A rising PSA anticipated bone progression by 6 to 12 months in 13 of 28 patients (46%). The PSA at entry to the trial was related to survival; a discriminant of 300 ng/ml distinguished a poor and better risk group. The lowest level of PSA reached during the first 6 months of treatment was also a univariate survival factor.

Topics: Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Buserelin; Flutamide; Goserelin; Humans; Male; Orchiectomy; Predictive Value of Tests; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Survival Rate

Topics: Buserelin; Drug Implants; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Palliative Care; Prostatic Neoplasms

One hundred eighteen patients with stage D (D1 or D2) prostate cancer with a mean age of 69 years were treated with monthly goserelin (Zoladex; ICI 118, 630; ICI Americas Inc, Wilmington, DE, property of Imperial Chemical Industries PLC) injections and the data were analyzed for predictive parameters for best response and time to treatment failure (National Prostatic Cancer Project [NPCP] and Eastern Cooperative Oncology Group [ECOG] criteria). For best response in a univariate analysis, the performance status (PS 0-1 v 2-3) (P = .01), hematocrit (P = .04), and pain (P = .04) were significant. For time to treatment failure by univariate analysis, ECOG performance status (0-1 v 2-3) was most predictive (P less than .0001), followed by pain at entry (P = .0002), initial testosterone (T) level (greater than 250 ng/dL) (P = .0005), age less than 69 years (P = .02), alkaline phosphatase (less than 115 IU/L) (P = .03), hemoglobin (less than 14 g/dL) (P = .03), whereas normal acid phosphatase (less than 3 IU/mL) (P = .29) was not predictive. In multivariate analysis for time to treatment failure, only the ECOG performance status was of significance (P = .01). Estimated median time to treatment failure for PS of 0-1 was 88 weeks and for PS of 2-3 was 31 weeks.

Topics: Age Factors; Aged; Alkaline Phosphatase; Analysis of Variance; Antineoplastic Agents; Buserelin; Goserelin; Health Status; Humans; Male; Multivariate Analysis; Neoplasm Staging; Pain; Predictive Value of Tests; Proportional Hazards Models; Prostatic Neoplasms; Remission Induction; Testosterone

Orchiectomy was performed in 16 patients because of progression of prostatic cancer despite adequate medical castration with goserelin (Zoladex, ICI) over a mean period of 17.6 months. Severe tubular atrophy was seen in the testes. The Leydig cells also showed signs of atrophy, a fact that may indicate a direct effect of goserelin on these cells. In 1 patient, however, orchiectomy was postponed for 3 months after cessation of medical castration. The serum testosterone had resumed almost normal values and testicular histology revealed intact spermatogenesis and apparently normal Leydig cells.

Topics: Aged; Buserelin; Goserelin; Humans; Leydig Cells; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Spermatogenesis; Testis; Testosterone; Time Factors

Chronic treatment with the GnRH (gonadotrophin hormone releasing hormone) agonist Zoladex causes suppression of testicular androgens. Use of antiandrogens has been advocated to block the effects of the initial surge of androgens, and to block any presumed effects of adrenal androgens. We have measured plasma concentrations of androgens and possible precursors before and during treatment in the following prostate cancer patients: 10 who received Zoladex alone (Z), nine who received Zoladex + the anti-androgen flutamide (Z + F) and five who were orchidectomized (O). Testosterone fell in the Z + F group to 0.84 +/- 0.21 nmol/l (mean +/- SD) significantly lower (Wilcoxon P less than 0.05) than after Z (1.58 +/- 1.84 nmol/l) alone. Progesterone and 17 alpha-hydryxyprogesterone did not change significantly in any group. Androstenedione and dehydroepiandrosterone sulphate (DHAS) showed significant falls in Z + F (from 3.44 +/- 0.34 to 1.92 +/- 0.18 mumol/l and from 3.88 +/- 0.64 to 1.92 +/- 0.36 mumol/l respectively) but not in other groups. These results are consistent with our demonstration of an inhibitory effect of flutamide, hydroxyflutamide and other antiandrogens on human adrenal microsomal 17 alpha-hydroxylase and 17,20-lyase activities in vitro.

Topics: 17-alpha-Hydroxyprogesterone; Aged; Aged, 80 and over; Androgens; Androstenedione; Anilides; Antineoplastic Agents; Buserelin; Dehydroepiandrosterone; Depression, Chemical; Flutamide; Goserelin; Humans; Hydroxyprogesterones; Male; Orchiectomy; Prostatic Neoplasms; Testosterone

Serum bioactive and immunoreactive LH and FSH were measured in clinical conditions with increased or decreased gonadotropin secretion. Gonadotropin immunoreactivity was measured using a conventional RIA (I) and an ultrasensitive immunofluorometric method (F). Bioactive (B) LH was assessed by the mouse interstitial cells in vitro bioassay, and B-FSH using the immature rat granulosa cell assay. Acute GnRH stimulation of adult men (n = 6) increased LH levels measured by the different methods 4.3- to 5.3-fold. The B/I ratio of LH increased from 2.34 +/- 0.21 to 3.71 +/- 0.36 (mean +/- SEM) at 120 min (P less than 0.05), but no change was found in the B/F ratio. After ovariectomy of premenopausal women (n = 6), the LH levels increased in 1 week 4- to 6-fold, the B/I ratio from 1.85 +/- 0.22 to 2.59 +/- 0.24, and the B/F ratio from 1.78 +/- 0.22 to 2.90 +/- 0.30 (P less than 0.05 for both). In addition, the LH levels were measured during GnRH agonist treatment of ovarian carcinoma (n = 8), endometriosis (n = 8), and prostatic carcinoma after orchiectomy (n = 8). In the two former groups, serum B-LH decreased in 1 month to undetectable levels (less than 0.5 IU/L), and in the prostate cancer patients to 1.2 (0.8-1.9) IU/L (log mean and range of +/- SEM). The concomitant decline of I-LH was to 1.5-1.9 IU/L in the agonist-treated female patients, and that of F-LH to 0.10-0.15 IU/L; in the prostate cancer patients, respectively, these values were 7-8 and 0.3-0.7 IU/L. The B/I and B/F ratios during the agonist treatments could only be calculated in the prostate cancer patients (in the others, B-LH became undetectable). The B/I ratio decreased from 2.34 +/- 0.5 to 0.14 +/- 0.03 (P less than 0.01), but no suppression was found in the B/F ratio from a pretreatment value of 3.6 +/- 0.8. B-, I-, and F-FSH levels were measured in the GnRH agonist-treated orchiectomized prostate cancer patients. The pretreatment level of B-FSH was 154 (137-175), that of I-FSH was 38.0 (34.4-42.0), and that of F-FSH was 39.8 (35.3-44.9) IU/L. The B/I ratio of FSH was 3.76 +/- 0.49, and the B/F ratio was 3.53 +/- 0.59. The mean B-FSH level decreased during treatment by 87-93.5%, that of I-FSH by 98%, and that of F-FSH by 91.5% (P less than 0.01 for all).(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; Aged; Biological Assay; Buserelin; Endometriosis; Female; Fluorescent Antibody Technique; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Menopause; Middle Aged; Nafarelin; Orchiectomy; Ovarian Neoplasms; Ovariectomy; Prostatic Neoplasms; Radioimmunoassay; Uterine Neoplasms

Topics: Buserelin; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms

The toxicity and side effects of combination therapy with zoladex and flutamide have not been excessive compared with those due to orchidectomy. Pain due to the flare phenomenon has not been observed with zoladex and flutamide. Treatment modification has been necessary in 12 of the 149 patients receiving the combination therapy, compared with one of 148 patients who had surgical castration. Only one patient had flutamide withdrawn because of diarrhea and only five patients had treatment modification because of liver toxicity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Buserelin; Flutamide; Goserelin; Humans; Male; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms

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

79 patients with locally advanced and/or metastatic prostate cancer were treated by means of a biodegradeable depot formulation of the luteinizing hormone releasing hormone analogue Goserelin (Zoladex). All patients received 3.6 mg depot Goserelin (Zoladex 3.6 mg implantate) subcutaneously into the anterior abdominal wall at 4 weekly intervals. The average time of observation was 24.2 months. The best objective response rate was found in 62%. Serum testosterone levels initially increased after the first depot injection and then decreased ultimately to castrate range (less than 0.6 ng/ml) between day 15 and day 27 (median 21) in the majority of patients. Castrate testosterone levels were still found 48 months after the start of treatment with depot Goserelin. 6 months after institution of treatment in 66.7% of cases evident signs of histological regression were found in the primary tumour tissue. Adenocarcinoma presented with a highly significantly better response pattern than anaplastic carcinoma. In animal experiments a single dose of 1 mg depot Goserelin was administered to adult male rats and the effect on serum testosterone levels and target organs (testes and ventral prostate) were investigated. Mean testosterone levels (mean = 0.31 ng/ml) decreased to castrate range (less than 0.3 ng/ml). 4 weeks after depot injection weight of the testes and prostate weight were significantly reduced. However 8 weeks after administration of 1 mg depot Goserelin there was no significant between the control group and the treated group. We conclude that the depot formulation of Goserelin (Zoladex) is effective, simple, practicable and safe in the treatment of advanced prostatic cancer. Current clinical studies are confirming the importance of reversible medical castration by LHRH agonists before radical prostatectomy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Animals; Buserelin; Carcinoma; Drug Implants; Goserelin; Humans; Male; Middle Aged; Organ Size; Prospective Studies; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testis; Testosterone

A new depot formulation of the LHRH analogue Zoladex (goserelin acetate) has been developed which releases the drug over a period of at least 3 months as judged by measurement of drug content in depots at intervals after insertion in male rats and by the suppression of oestrogen secretion and oestrus in female rats. This formulation is based on the lactide/glycolide polymer system used for the standard 1-month Zoladex depot, but the dose has been increased to 10.8 mg and the characteristics have been modified to enable a longer release of drug to be achieved. Thirty-eight patients with histologically proven, locally advanced (stage T3 or T4) and/or metastatic prostate cancer were treated with this new longer acting LHRH analogue depot formulation containing 10.8 mg Zoladex. After initial increase of serum testosterone in the first week of therapy, castration levels were reached in all patients after 4 weeks and this was maintained for more than 14 weeks. At the time of depot exhaustion, when escape from castration levels of androgen occurred, all patients received a single injection of a standard 1-month depot containing 3.6 mg Zoladex which restored castration levels of androgen thus showing that the pituitary gland was again suppressed. The tolerance and acceptability of the longer-acting depot is high and comparable to the 1-month depot. Taking into account social and psychological factors, patients with advanced prostate carcinoma will soon be able to be treated with a longer acting LHRH depot formulation every 3 months an alternative of the 1-month depot now widely used clinically.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Buserelin; Drug Tolerance; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Pituitary Gland; Prostatic Neoplasms; Testosterone

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cyproterone Acetate; Disease Progression; Goserelin; Humans; Male; Neoplasm Staging; Prostatic Neoplasms; Survival Analysis; Treatment Outcome

Given the current preference of many patients for an active role in decision-making regarding their care, the feasibility of patients making their own treatment choices was investigated, and the reasons for their selections were studied. Subjects comprised previously untreated Stage D prostate cancer patients for whom hormonal therapy was indicated. Thirteen institutions entered 159 patients into the study. After discussing treatment choices with their physicians, the patients took home a two-page letter explaining two options: surgical castration and therapy with Zoladex (goserelin acetate), a depot luteinizing hormone-releasing hormone (LHRH) analogue injected subcutaneously every twenty-eight days. Patients were encouraged to discuss the treatment choices with their families. After selecting a treatment approach, patients completed a "decision questionnaire" and then treatment was initiated. Of the 147 patients who completed baseline questionnaires, 78 percent selected Zoladex and 22 percent selected orchiectomy. The primary reason for selecting Zoladex included avoidance of surgery (36%), success of treatment (18%), convenience of the drug (10%), and physician's advice (10%). Patients chose surgery primarily because of convenience (32%) and success of treatment (29%). Three months later, patients and their wives completed another questionnaire, which assessed their satisfaction with their treatment choices. Ninety-three percent of patients and 91 percent of patients' wives indicated that they would select the same treatment again.

Topics: Adult; Aged; Aged, 80 and over; Attitude to Health; Buserelin; Consumer Behavior; Decision Making; Follow-Up Studies; Goserelin; Humans; Informed Consent; Male; Middle Aged; Orchiectomy; Patient Participation; Prostatic Neoplasms; Surveys and Questionnaires

Topics: Buserelin; Castration; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms

A luteinizing hormone-releasing hormone (LH-RH) analogue was administered for 3 to 32 months to 15 prostatic cancer patients in stage B-D (B:3, C:8, D:4). Intratesticular, intratubular and prostatic androgen levels were measured by radioimmunoassay before and after LH-RH analogue therapy. The measurement of serum prostatic acid phosphatase (PAP) and prostatic specific antigen (PA) levels was also conducted. Thereafter, we assessed the effect of the LH-RH analogue on androgen levels and the relation of prostatic tissue 5 alpha-dihydrotestosterone (DHT) level to the clinical response. The results were as follows: 1) Johnsen's mean germinal epithelium count was significantly decreased from 7.7 +/- 2.1 (mean +/- S.D.) to 4.3 +/- 2.3, and the wall thickness of seminiferous tubules was increased from 5.93 +/- 1.31 to 11.9 +/- 3.64 microns. 2) Plasma testosterone (T), intratesticular and intratubular androgen levels were significantly decreased (plasma T: from 4.40 +/- 1.84 to 0.61 +/- 0.32 ng/ml, intratesticular T: from 335.3 +/- 170.3 to 4.6 +/- 3.8 ng/g.t.w., DHT: from 25.3 +/- 11.7 to 3.7 +/- 2.7 ng/g.t.w., intratubular T: from 50.8 +/- 36.6 to 0.10 +/- 0.99 ng/g.t.w. and DHT: 7.54 +/- 3.20 to 0.63 +/- 0.90 ng/g.t.w.). 3) Crude nuclear DHT levels in prostatic tissue fell from 15.3 +/- 9.3 (N = 8) to 0.37 +/- 0.54 pg/mg protein (N = 3) and the level was non-detectable in 5 of 8 cases. 4) Complete remission was achieved in 1 patient, partial response in 5, objective stable in 8, and objective progression in 1 patient, according to Shimazaki's criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgens; Antineoplastic Agents; Buserelin; Dihydrotestosterone; Drug Evaluation; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Remission Induction; Testosterone

Topics: Aged; Aging; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Flutamide; Goserelin; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Male; Middle Aged; Prostatic Neoplasms; Testosterone

In the treatment of advanced prostate cancer, luteinising hormone-releasing hormone analogue monotherapy is a valuable alternative to standard treatment such as oestrogen therapy or surgical castration. The basis for this is discussed and reference is made to posters presented at the International Symposium on Endocrine Therapy.

Topics: Buserelin; Goserelin; Humans; Male; Prostatic Neoplasms

Treatment of advanced prostate cancer with a combination of luteinising hormone-releasing hormone analogues and anti-androgens is advisable for the initial 2 weeks, in patients with newly diagnosed, extensive disease. Advances in long-term combination treatment are questionable until results of phase III studies become available. Reference is made to poster presentations at the International Symposium on Endocrine Therapy.

Topics: Androgen Antagonists; Buserelin; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms

To prevent progression of sex hormone-responsive prostate and breast tumours, anti-androgens and anti-oestrogens are commonly used to induce androgen and oestrogen withdrawal. Zoladex is a potent luteinising hormone-releasing hormone agonist analogue, which has a selective effect on pituitary gonadotrophin release, and is highly effective at inducing regression of sex hormone-responsive prostate and breast tumours. Its depot formulation, active for at least 28 days, is convenient to administer and well tolerated and for the treatment of sex hormone-responsive tumours in men and women, Zoladex is an effective alternative to surgery.

Topics: Animals; Buserelin; Female; Goserelin; Male; Mammary Neoplasms, Experimental; Prostatic Neoplasms; Rats

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

A long-acting LRH agonist (ICI 118630, Zoladex) was given by monthly subcutaneous injection to 25 patients with previously untreated symptomatic advanced prostatic carcinoma. The medication was well tolerated with the only side effect being hot flushes in 15 patients. Subjective improvement occurred in 22 patients, and disease remission or stabilization judged by objective criteria was seen in 21 and 18 patients from the total group at 3 and 6 months of treatment, respectively. Twelve of 18 patients followed for 1 year were still in objective remission/stabilization. Prostate volume measured by ultrasound decreased by a mean value of 75% and urine flow increased significantly. There were significant falls in serum testosterone and gonadotrophin levels and significant although lesser reductions in serum androstenedione and dehydroepiandrosterone. These changes were accompanied by significant reductions in serum acid and alkaline phosphatase and a rise in serum osteocalcin. Four patients (16%) experienced an initial tumor flare. Although only a small number of patients were studied, Zoladex appeared to be a well-tolerated agent for treatment of prostatic carcinoma, with an initial clinical response similar to that seen with standard endocrine therapy.

Topics: Adult; Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Pain; Prostatic Neoplasms; Ultrasonography

Medical castration obtained with luteinizing hormone releasing hormone (LHRH) analogues in patients with prostate cancer is now well established. To block the initial stimulation of testosterone production and prevent the risk of the so-called flare-up with this medication, we investigated short-term combination therapy with 1 mg of diethylstilbestrol (DES). Fourteen previously untreated patients with histologically proved metastatic prostatic carcinoma were treated with 1 mg DES po daily one week prior to the initiation of therapy with LHRH analogues depot injection of Zoladex (ICI 116630) and continued during four weeks after the first depot injection. LHRH depot form was maintained as long as patients experienced clinical benefit. Endocrinologic results show that in spite of 1 mg of DES a significant increase of testosterone is still observed in the first week after injection of the LHRH depot form. Hence, this combination is not useful to prevent endocrinologic and clinical flare-up in patients with prostate cancer treated with LHRH analogues.

Topics: Aged; Buserelin; Diethylstilbestrol; Drug Evaluation; Drug Therapy, Combination; Goserelin; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Testosterone

We treated 191 patients with histologically proved locally advanced stage (T3 or T4) and/or metastatic prostate cancer with a biodegradable depot formulation of a luteinizing hormone-releasing hormone analogue (Zoladex). After an initial increase in serum testosterone in week 1 of therapy a continuous decrease of testosterone to castrate levels was obtained. With a monthly injection of the luteinizing hormone-releasing hormone analogue 4 patients (2 per cent) experienced a transient increase in bone pain, 1 had ureteral obstruction and 1 suffered paraplegia during the first few weeks of therapy. Over-all objective and subjective responses were similar to those obtained by castration or estrogen therapy. The absence of local and systemic (long-term) side effects proves the validity of this approach for patients with advanced prostatic cancer.

Topics: Aged; Aged, 80 and over; Buserelin; Carcinoma; Drug Administration Schedule; Goserelin; Humans; Injections, Subcutaneous; Male; Middle Aged; Prostatic Neoplasms; Testosterone

Transrectal ultrasonography has proved valuable in assessing the effect of primary treatment modalities for prostate carcinoma. This study shows patients who had a significant reduction in primary tumor volume had a significantly better prognosis and had less local symptoms than did the group of patients that did not have a significant reduction (less than 50%) in primary volume secondary to therapy. Patients were treated with either castration or Zoladex and all had Stage D2 cancer of the prostate.

Topics: Aged; Buserelin; Carcinoma; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Ultrasonography

We treated 38 patients with newly diagnosed advanced prostatic cancer with monthly injections of a long acting depot preparation of a luteinizing hormone-releasing hormone superagonist (Zoladex depot). After 6 months' treatment 10% of the patients had complete objective regression, 77% had partial objective regression, 3% stable disease and 10% had objective progression. The LHRH analogue does not have the metabolic side effects of oestrogens. Depot luteinizing hormone-releasing hormone analogue may well become a preferred alternative for patients with advanced prostatic cancer.

Topics: Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Drug Administration Schedule; Estradiol; Estradiol Congeners; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Time Factors

In patients with histologically confirmed prostate cancer, oestrogen priming with diethylstilboestrol (DES) (3 mg/day) for 4 weeks prior to the first injection of the LHRH agonist Zoladex (3.6 mg depot form) prevented any rise in the serum testosterone concentration. In contrast, in the groups pre-treated with DES, the first, but not subsequent, injections with Zoladex were associated with a marked surge in luteinising hormone. Treatment with DES beyond the time of the first administration of Zoladex did not provide further endocrinological advantage. Oestrogen priming for 1 month prior to treatment with Zoladex may prevent an exacerbation of signs and symptoms of prostate cancer.

Topics: Buserelin; Diethylstilbestrol; Goserelin; Humans; Luteinizing Hormone; Male; 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

Topics: Buserelin; Drug Evaluation; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Substance Withdrawal Syndrome; Testosterone

Fifty-six patients with previously untreated advanced prostatic cancer were treated with the LH-RH agonist Zoladex. Patients have been followed for between 24 and 39 months. The response rate and duration of response have been assessed and related to the degree of differentiation of the primary tumor. All of the patients with well-differentiated tumors responded symptomatically, while the comparable figure for patients with poorly differentiated tumors was 67%. The better differentiated tumors tended to respond longer than their poorly differentiated counterparts (18.75 months compared to 15.9 months, respectively). Overall survival was worse in patients having tumors of higher grade and the mean survival after relapse was shorter. The results confirm the unfavorable prognostic significance of poor histological grade in prostatic cancer and indicate that response to treatment, duration of response, and time to death following relapse are also adversely influenced.

Topics: Buserelin; Follow-Up Studies; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Pain; Prognosis; Prostatic Neoplasms; Testosterone; Time Factors

Eighty patients with prostatic cancer have been treated with an LH-RH analogue (Zoladex). Ten had no metastasis, and hormone therapy was used as an induction treatment before curative radiotherapy. The others had metastatic disease and, in some cases, had already received some form of endocrine therapy. Patients received a monthly injection of Zoladex (3.6 mg). No progressive disease was noted among patients with nonmetastatic tumors; of the patients with metastases, those who were previously untreated had a higher response rate (14.8% complete response) and longer progression-free and overall survival. Toxicity was mild in spite of two cases of disease flare.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Buserelin; Carcinoma; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Remission Induction

The trial drug was ICI 118.630 (Zoladex). Inclusion criteria were histologically confirmed advanced prostate cancer (T greater than 2 or N+ or M+), life expectancy greater than 3 months, and no previous radiotherapy, orchiectomy, or chemotherapy. Treatment started in November 1984; 30 patients were recruited. The period of treatment ranged from 6 to 144 weeks (median of 59.5 weeks). One patient died after 6 weeks of rapidly progressive renal failure. Data were updated to the end of August 1987. The mean age was 67.9 years (53-83 years). Subjective response was evaluated by a mean symptoms score (using daytime micturition, nocturia, dysuria, hesitancy, and flow) and a score of three different items: patients' activity, bone pain, and use of analgesics. Only 7.1% of the patients showed a permanent positive response. Four different objective responses (complete, partial, stable disease, and progression) were possible after evaluating the T category, tumor dimensions, metastases, and prostatic acid phosphatase. Testosterone (T) and plasmatic LH levels rose after administration: T dropped below the castration level (1 ng/ml) within a few days and remained constantly low. The rate of progressive disease was 27.6%; disease control was possible in 72.4% of the patients (PR or SD).

Topics: Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Follow-Up Studies; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Middle Aged; Neoplasm Staging; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Remission Induction; Testosterone

The depot LH-RH agonist Zoladex was used to treat 38 patients with previously untreated symptomatic stage D2 prostate carcinoma. Side effects were minimal and patient acceptability excellent, although temporary tumor flare occurred in 11% of patients. Eighty-four percent experienced subjective improvement and 87% had objective evidence of initial disease stabilization or remission lasting 3 months. Serum levels of gonadotrophin and free testosterone as well as androgens of adrenal origin fell significantly with treatment. Long-term survival to date appears at least as good as that described for conventional endocrine therapy.

Topics: Buserelin; Carcinoma; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Male; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Remission Induction; Testosterone

It is well known that the first administration of luteinizing hormone releasing hormone (LH-RH) analogues induces an initial increase of luteinizing hormone (LH) release and a subsequent rise in testosterone (T). This rise is maximal after 3-4 days and is followed by a steady fall of LH and T. Several investigators have reported flare-up symptoms in patients with advanced prostatic cancer, associated with the rise of T, when treated by LH-RH analogue alone. In order to prevent these flare-up symptoms, we treated 20 patients with advanced prostatic cancer with an association of a LH-RH analogue (Zoladex Depot) and diethylstilbestrol (DES) 1 mg/day. DES was given for 14 days, starting 7 days before the first Zoladex Depot injection. T fell to near castrate levels within a few days, but rose again 3-4 days after the administration of the LH-RH analogue to pretreatment values before returning to castrate levels. No clinical flare-up manifestations were recorded. We conclude that combination treatment with DES can prevent the flare-up symptoms induced by LH-RH analogue in patients with prostatic cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Delayed-Action Preparations; Diethylstilbestrol; Follicle Stimulating Hormone; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Testosterone

Endocrine therapy for urological tumor includes estrogen therapy for prostatic carcinoma. This endocrine therapy is one of the most firmly established therapeutic methods in the field of clinical oncology. However, confusion exists about how long this treatment remains effective and whether it prolongs survival, since estrogen can create cardiovascular complications in patients with prostatic carcinoma. Recently, new endocrine agents have been developed to compensate for the problems of estrogen therapy and to make treatment more effective. Estramustine sodium phosphate is medicine for internal use prepared by combining estradiol with nitrogen mustard. This hormonal chemotherapeutic agent has proved effective in 98% of treated patients. Most of the side effects of this agent have been observed in the digestive organs. Chlormadinone acetate, a progestational agent, has proved more effective against early prostatic carcinoma than against late-stage disease. LHRH analogue, which is now drawing much attention as a "chemical castration" agent for prostatic cancer patients, exerts an effectiveness equal to medium-dose estrogen treatment. The above three agents for the treatment of prostatic carcinoma should become increasingly popular in the future.

Topics: Buserelin; Chlormadinone Acetate; Estramustine; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Nitrogen Mustard Compounds; Prostatic Neoplasms

We treated 37 patients with newly diagnosed advanced prostatic cancer with monthly injections of a long acting depot preparation of a luteinizing hormone-releasing hormone superagonist. Serum testosterone levels were reduced to and maintained within the castrate range, even in cases of objective progression. The partial objective regression rate was 43 per cent, with 36 per cent of the patients having objectively stable disease and 21 per cent having objective progression. The subjective improvement rate was 67 per cent. The addition of a short course of diethylstilbestrol at the initiation of therapy appeared to shorten the delay for the subjective improvement. Patient acceptance was excellent and side effects were minimal. Depot luteinizing hormone-releasing hormone analogues, alone or in combination, may well become a preferred alternative treatment for patients with advanced prostatic cancer.

Topics: Aged; Buserelin; Carcinoma; Delayed-Action Preparations; Diethylstilbestrol; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Testosterone

The antitumor effect and safety and endocrinological effect of a depot formulation of luteinizing hormone-releasing hormone (LH-RH) analogue ICI 118630 (Zoladex) were studied. Each depot containing 3.6 mg of ICI 118630 (corresponding to the average daily release of 120 micrograms) was subcutaneously injected 3 times at 4 week intervals to 12 prostate cancer patients in total at 4 centers from August 1984 to March 1985. Of the 12 patients, 7 showed an objective clinical response (1 CR and 6 PR patients), 3 showed no change and the remaining 2 showed PD. Overall subjective improvement was obtained in 8 of 10 patients (80.0%). Serum hormone levels (LH, FSH, and testosterone) increased immediately after injection of depot and then significantly decreased during and after 2 weeks of treatment. These changes seen in 100% of the patients were attributable to the pharmacological action of the drug. Medical castration was attained in 3.1 +/- 0.9 weeks on average. Observed side effects included gynecomastia in 1 and hyperlipidemia in 2 patients which were all mild. The trial was continued in the patients who required no special medical treatment. Changes in blood Zoladex concentrations suggested no accumulation. These findings demonstrate the safety and useful endocrinological and antitumor effects of Zoladex in prostate cancer through its pharmacological action, that is, LH-RH agonistic action.

Topics: Aged; Buserelin; Delayed-Action Preparations; Drug Administration Schedule; Drug Evaluation; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone

The clinical and endocrine response to a depot preparation of the LH-RH analogue ICI 118630 (Zoladex) was assessed in 55 untreated patients with advanced prostatic cancer. Whereas gonadal androgen suppression was achieved in all patients, subjective and objective clinical response occurred in only 69%, indicated by a relief of bone pain, a decrease in the size of the primary tumour and lymph node metastases and improvement in bone scan appearances. A third of these patients, however, subsequently showed progression of their disease. Serious side effects were not encountered in this study. The depot formulation is a simple, safe and convenient method of administering Zoladex and offers an alternative treatment for metastatic prostatic cancer.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Buserelin; Delayed-Action Preparations; Goserelin; Humans; Luteinizing Hormone; Lymphatic Metastasis; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Random Allocation; Testosterone

Topics: Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms

Topics: Buserelin; Goserelin; Humans; Male; Prostatic Neoplasms

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

Topics: Buserelin; Drug Evaluation; Goserelin; Humans; Male; Prostatic Neoplasms

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

Topics: Androgen Antagonists; Buserelin; Estrogens; Goserelin; Humans; Male; Prostatic Neoplasms

Eleven patients with prostatic cancer maintained on monthly depot Zoladex (ICI 118,630) from 20 to 23.5 months are described. All are in clinical remission. Castrate levels of testosterone are maintained, and low levels of LH and FSH were observed. Contrary to a prior report, persistent blockage of the pituitary-gonadal axis is achieved and maintained with no detectable adverse side effects.

Topics: Buserelin; Delayed-Action Preparations; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Pituitary Gland; Prostatic Neoplasms; Testis; Testosterone; Time Factors

Six prostatic cancer patients were treated with a gonadotropin-releasing hormone agonist analog (ICI 118630, ICI Pharmaceutical Division, Macclesfield, England) for 4 weeks, and serum testosterone (T) had fallen to the castration level in all patients. Subsequently, three of the patients were orchiectomized. There were no significant differences in follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG) receptors between the testes treated with ICI 118630 and testes obtained from untreated prostatic cancer patients. In the other three patients, testicular responsiveness evaluated using hCG stimulation was similar before and after 4 weeks of treatment. In vitro studies testes removed from untreated prostatic cancer patients were cultured in a medium with or without ICI 118630 for 5 days. There were no significant differences in FSH and hCG receptors and T production between the two groups. In conclusion, ICI 118630 had no direct inhibitory effect on human testes.

Topics: Aged; Buserelin; Chorionic Gonadotropin; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Organ Culture Techniques; Prostatic Neoplasms; Receptors, FSH; Receptors, LH; Testis; Testosterone

Topics: Aged; Buserelin; Goserelin; Humans; Injections, Subcutaneous; Male; Middle Aged; Prostatic Neoplasms

The effects of luteinizing hormone-releasing hormone (LHRH) agonist (Zoladex) treatment on hormone-dependent rat prostate adenocarcinoma (R3327-H) were investigated based on changes in tumor volume and histology. Tumor-bearing rats were treated for 10 weeks with Zoladex in depot preparation by implantation every 2, 4, or 6 weeks. Tumor growth rate was similar in the castrated group and in the rats treated every 2 weeks with Zoladex. This growth rate was significantly slower than in animals treated with Zoladex every 6 weeks and the nontreated group. The growth rate in rats treated every 4 weeks appeared to be faster than that in the castrated animals (not significant). Changes in testosterone levels measured during Zoladex treatment correlated with tumor growth kinetics. Zoladex implantation yields effective and complete androgen deprivation only in the rats with two weekly depot renewal regimen. Tumor histology indicated that the stromal as well as the glandular epithelial cells responded to both castration and to Zoladex treatment. However, in tumors from rats treated with Zoladex every 4 and 6 weeks progressive increasing signs of restoration of normal elements, comparable to non-treated tumors were observed. These results strongly suggest that careful attention has to be paid to the timing of LHRH depot renewal in prostate cancer treatment.

Topics: Androgens; Animals; Buserelin; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Goserelin; Kidney; Male; Neoplasms, Hormone-Dependent; Organ Size; Prostate; Prostatic Neoplasms; Rats; Seminal Vesicles; Testis; Testosterone

Topics: Aged; Aged, 80 and over; Buserelin; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms

Zoladex is a potent decapeptide analogue of luteinising hormone releasing hormone (LHRH). The drug is formulated as a 3.6 mg depot dispersed in a matrix of d,l-lactide-glycolide copolymer, which is totally biodegradable. This formula releases drug continuously for at least 28 days and reliably suppresses serum testosterone into the castrate range. The effect of the depot was studied in 29 patients with locally advanced or metastatic carcinoma of the prostate. Average age at entry was 71 years (range 52-87) and follow-up was from 13.5 to 34.5 months (median 23). Endocrine studies showed that medical castration was maintained in all cases. Three patients experienced bone pain in the first month of treatment and two others had temporary nephrostomies for worsening ureteric obstruction. Subjective improvement was seen in 23/28 cases (82%). There were no complete responses, but partial response was seen in 24/28 (85.7%) using our own criteria, 24/28 (85.7%) using the criteria recommended by the British Prostate Group (BPG) and 15/28 (53.6%) using NPCP criteria. Stable disease was seen in 3/28 patients (10.7%) by our own or BPG criteria, and in 12/28 patients (42.9%) according to NPCP criteria. Progression of disease was measurable in 21 patients (72.4%) whatever criteria were applied; 11/29 (37.9%) have died, giving a median survival of 10 months (range 2.4-26). Following these encouraging results, a multicentre randomised comparative study with stilboestrol 3 mg daily is being undertaken.

Topics: Aged; Aged, 80 and over; Buserelin; Castration; Delayed-Action Preparations; Drug Evaluation; Goserelin; Humans; Male; Middle Aged; Prognosis; Prostatic Neoplasms

Nine elderly men with prostatic carcinoma underwent treatment with a LHRH-agonist (Zoladex, ICI) for 3-6 months. At the end of the treatment period the patients underwent subcapsular orchidectomy. Testicular tissue was incubated with different tritiated testosterone precursors. Conversion mediated by several testicular steroidogenic enzymes was compared between Zoladex-treated patients and nineteen non-treated patients who underwent orchidectomy because of prostatic carcinoma. Serum concentrations of LH, FSH and testosterone were determined before and during treatment in the treated patients. The LHRH agonist treatment induced significantly decreased conversion mediated by the enzymes 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase and C17-20 lyase. Conversion mediated by 17 beta-ketosteroid reductase was also decreased although not as dramatically as the other enzymes, while conversion mediated by 20 alpha-dehydrogenase was increased. Serum concentrations of testosterone decreased to castration levels. Serum gonadotrophins decreased but remained within normal levels suggesting that "desensitization" at the pituitary level was not the only mechanism of action of the LHRH-agonist.

Topics: Aged; Aged, 80 and over; Buserelin; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Orchiectomy; Prostatic Neoplasms; Testis; Testosterone

The levels of prostatic specific antigen (PSA) and prostatic acid phosphatase (PAP), both measured by radioimmunoassay, and two cancer indices given by the ratio of serum alpha-1 acid glycoprotein to prealbumin (AGP:Palb) and alpha-1 acid glycoprotein to alpha-2 HS globulin (AGP:HS) were evaluated as markers to assess the response of prostatic cancer to treatment with Zoladex, an LH-RH agonist. A rise in PSA and PAP occurred in 8/65 patients (12%) during the initial induction phase. In metastatic disease prior to treatment none of these indices was significantly different between patients who attained a sustained response and those whose response was nil or only transient. Responders and non-responders could, however, be distinguished by the levels of various analytes after treatment. At 6 months the median PSA in those who responded was 2.5 ng/ml compared with 51.5 ng/ml in the non-responders. At 12 months the figures were 3.0 and 155 ng/ml respectively. The corresponding median PAP levels were 1.4 and 19 ng/ml at 6 months and 1.3 and 18 ng/ml at 12 months. The AGP:Palb ratio was also significantly different in these two groups at 6 and 12 months. PSA appears to be the most sensitive indicator of the response to treatment. The likelihood of obtaining a prolonged clinical response can be assessed within 6 months of the start of treatment.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; alpha-2-HS-Glycoprotein; Antigens; Blood Proteins; Buserelin; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Orosomucoid; Prolactin; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Testosterone

Topics: Aged; Antithrombin III; Buserelin; Goserelin; Humans; Male; Middle Aged; 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

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

Twenty-four patients with advanced prostatic cancer were treated with daily injections of the LHRH analogue ICI 118630 (Zoladex) for up to 2 1/2 years. Successful long-term suppression of LH (luteinising hormone) and testosterone was observed without any escape of testosterone. Immunoreactive LH concentrations rose significantly following the daily injection of LHRH analogue but there was no corresponding rise in testosterone concentrations, suggesting altered bioactivity of the LH. A long-term clinical response was obtained in 10 patients (41.6%) and the median duration of response in these patients was 25 months. Eight of the 10 had well to moderately differentiated tumours. The actuarial median survival of all patients was 22 months.

Topics: Aged; Aged, 80 and over; Buserelin; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Time Factors

Diurnal profiles of circulating gonadotrophins and testosterone have been measured in patients with prostatic carcinoma on long-term treatment with the LHRH agonist analogue ICI 118630, which was administered either by subcutaneous daily injection or monthly injection of the depot preparation. These have been compared with profiles in patients who had undergone orchiectomy. Daily injection of the analogue induced a significant rise in the level of LH but this was not associated with a significant rise in circulating testosterone. There was no diurnal variation of LH or testosterone concentration in patients receiving the depot preparation and this did not differ in patients who were "mid-cycle" compared with those who were "end-cycle". The depot preparation did, however, induce significantly lower circulating levels of testosterone than did daily injection of the analogue and the levels were comparable with those achieved after orchiectomy.

Topics: Aged; Aged, 80 and over; Buserelin; Drug Administration Schedule; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Testosterone

Topics: Androgen Antagonists; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Carcinoma; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Triptorelin Pamoate

A study was conducted of the response of the pituitary-testicular axis to two different methods of administration of the luteinising hormone releasing hormone (LHRH) analogue ICI 118630 (Zoladex) in patients with prostatic cancer. The analogue was given by continuous infusion to four previously untreated patients with prostatic cancer for 60 days (group 1). Subsequently a further four patients were given a depot formulation of the same analogue by subcutaneous injection once every 28 days (group 2). Both methods of administration produced similar, successful suppression of luteinising hormone (LH) associated with a reduction of testosterone to castrate concentrations. The median basal testosterone concentrations before treatment in groups 1 and 2 were 20.6 and 14.1 nmol/l (5.94 and 4.07 ng/ml) respectively; these were reduced to 1.4 and 1.1 nmol/l (0.40 and 0.32 ng/ml) within four weeks of the start of treatment. The median basal LH concentration in groups 1 and 2 were 7.9 and 16.6 IU/1 respectively, which were suppressed to 2.6 and 2.4 IU/1 by four weeks. The suppression of LH and testosterone was maintained with continuous subcutaneous infusion for up to 60 days in group 1, and by subsequent injections of the depot every 28 days in group 2. The use of depot preparation of an LHRH analogue to suppress gonadotrophin and sex hormone secretion offers the convenience of once monthly injections when LHRH analogues are required for the long term treatment of elderly patients with prostatic cancer and children with precocious puberty.

Topics: Aged; Buserelin; Delayed-Action Preparations; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone

A radioimmunoassay is described for D-Ser (tBu)6 AZA Gly10 GnRH (ICI 118630) in serum of prostate cancer patients treated chronically with this peptide to produce a medical castration. With 125I-118630 as the label, and an anti-GnRH serum, the specificity of the assay is directed to the N-terminal end of the peptide, and putative degradation products have less than 6% cross-reactivity. The assay appears specific for intact 118630 which, after subcutaneous administration of 250 micrograms, has a half-time of disappearance from the serum of 4.9 +/- 0.4 h and a volume of distribution of 13.7 +/- 0.8 litres. Continuous subcutaneous infusion of 120 micrograms 118630/d gave stable serum concentrations of between 2-3 ng/ml for up to 63 d which were very similar to values predicted from pharmacokinetic analysis of the analogue clearance rate. This contrasts with the "peak and trough' pattern of serum 118630 levels measured in two subjects after 118630 administration from a subcutaneous implant containing 3.6 mg of peptide in a biodegradable formulation. Serum 118630 levels peaked at between 6-8 ng/ml 15 d after the implant and fell to less than 1 ng/ml at 29 d, immediately before the next implant. Serum 118630 levels following a second 3.6 mg implant were almost identical with respect to absolute concentration and time to peak value as after the first implant. This assay will be of value not only for evaluation of the pharmacokinetics of GnRH analogue release from new long-acting formulations, but also for correlation of serum peptide concentrations with pituitary gonadotroph desensitization.

Topics: Buserelin; Delayed-Action Preparations; Drug Implants; Goserelin; Humans; Infusions, Parenteral; Kinetics; Male; Prostatic Neoplasms; Radioimmunoassay

Patients with advanced breast cancer or advanced prostate cancer have been treated with an LH-RH-agonist ICI 118630. A chemical castration-like response has been achieved in all patients and is associated with clinical remission of the disease.

Topics: Breast Neoplasms; Buserelin; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

Topics: Animals; Buserelin; Delayed-Action Preparations; Female; Goserelin; Male; Mammary Neoplasms, Experimental; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Rats

Topics: Buserelin; Goserelin; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

The influence of the LH-RH agonist ICI 118630 on circulating levels of the pituitary gonadotrophins LH and FSH and the gonadal steroids oestradiol, progesterone, 17-hydroxyprogesterone and testosterone has been studied in phase I clinical trials of the drug in patients with advanced breast or prostate cancer. ICI 118630 initially stimulated plasma levels of LH and FSH. On continued treatment however, the drug reversed this response and produced a rapid decline in plasma testosterone and progesterone in male and female patients respectively. Plasma oestradiol concentrations equivalent to those seen in oophorectomised or postmenopausal women were eventually produced in all 5 female patients treated with ICI 118630. In one patient however persistent follicular activity occurred until her third menstrual cycle. No appreciable side effects of the drug were observed. These data indicate that ICI 118630 initiates a castration-like endocrine response and has potential in the treatment of hormone dependent tumours of the breast and prostate.

Topics: Breast Neoplasms; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Hydroxyprogesterones; Luteinizing Hormone; Male; Progesterone; Prostatic Neoplasms; Testosterone; Time Factors

Topics: Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone; Time Factors

Topics: Buserelin; Goserelin; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

Topics: Buserelin; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Neoplasm Metastasis; Prostatic Neoplasms; Testosterone

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

Seventeen patients with advanced progressive prostatic cancer who had relapsed or failed to respond to conventional endocrine therapy with oestrogens, orchiectomy or antiandrogens were treated with the LHRH analogue, ICI 118630. No significant objective tumour responses were seen, though 11 of 15 patients who presented with symptomatic metastatic bone pain had rapid short-term pain relief. The lack of objective clinical response seen in this study indicates no justification for the use of LHRH analogues in this group of patients. Though a significant subjective response was seen there was no added advantage over regular analgesics.

Topics: Acid Phosphatase; Alkaline Phosphatase; Analgesia; Bone Neoplasms; Buserelin; Goserelin; Hormones; Humans; Male; Prostatic Neoplasms

9 of 12 patients with advanced metastatic carcinoma of the prostate treated with luteinising-hormone-releasing-hormone (LHRH) analogue ICI 118630 for a mean period of 6 months showed objective evidence of response to treatment. Of 8 patients with bone pain, 7 obtained relief. After 6 weeks of treatment testosterone concentrations were reduced to castrate levels (range less than 2 to 5.5 nmol/l) from a pretreatment mean value of 15.7 nmol/l (range 10.3-24 nmol/l). Basal gonadotropin levels and gonadotropin responses to acute LHRH stimulation were suppressed within 2 weeks of treatment. However, the testosterone response to stimulation with human chorionic gonadotropin was unimpaired 4 weeks after the start of treatment. Therefore suppression of the basal testosterone concentration by ICI 118630 was due to inhibition of pituitary luteinising-hormone secretion rather than direct inhibition of testicular Leydig-cell function. ICI 118630 offers an alternative treatment to orchidectomy and oestrogen therapy.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Chorionic Gonadotropin; Depression, Chemical; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Pain; Pelvis; Prostatic Neoplasms; Radiography; Testosterone

Topics: Buserelin; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms

Ten patients with advanced progressive adenocarcinoma of the prostate were treated with a long acting analogue of gonadotrophin releasing hormone. Eight of these patients responded to treatment in terms of pain relief and clinical regression of tumour. Serum gonadotrophin and testosterone concentrations were significantly suppressed by the end of the second week of treatment, testosterone concentrations being comparable with those achieved by castration. The two patients who failed to respond had both relapsed previously when receiving conventional treatment, and neither showed any endocrine response to the analogue. Superagonists of gonadotrophin releasing hormone may be the treatment of choice in adenocarcinoma of the prostate, but further trials are required to establish long term safety and efficacy.

Topics: Acid Phosphatase; Aged; Dose-Response Relationship, Drug; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone

Topics: Adenocarcinoma; Aged; Drug Resistance; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Goserelin; Humans; Ketoconazole; Male; Prostatic Neoplasms