goserelin and bicalutamide

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 We searched in MEDLINE, EMBASE, Central, and Lilacs from inception to nowadays and saturated information for unpublished data in other sources.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 Although trials showed DES as similarly effective to another forms of ADT, evidences about cardiovascular toxicity in out of date high doses have discouraged its use.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

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

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

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

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

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

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

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 investigate the clinical effects of integrated traditional Chinese and Western medicine in the treatment of castration-resistant prostate cancer (CRPC).. A total of 54 CRPC patients were randomly divided into a control and a trial group, all treated by endocrine therapy (oral Bicalutamide at 50 mg per d plus subcutaneous injection of Goserelin at 3.6 mg once every 4 wk) and chemotherapy (intravenous injection of Docetaxel at 75 mg/m2 once every 3 wk plus oral Prednisone at 5 mg bid), while the latter group by Fuyang Huayu Prescription (a Traditional Chinese Medicine ［TCM］ prescription for tonifying yang and dispersing blood stasis) in addition, for a course of 24 weeks. Comparisons were made between the two groups of patients in the level of serum prostate-specific antigen (PSA), Karnofsky physical condition scores, function assessment of cancer therapy-prostate (FACT-P) scores, and TCM symptoms scores before and after 12 or 24 weeks of treatment.. Compared with the baseline, the serum PSA level was significantly decreased after 12 weeks of treatment both in the control (［25.9 ± 39.3］ vs ［20.0 ± 21.1］ μg/L, P <0.05) and in the trial group (［22.1 ± 33.9］ vs ［17.9 ± 19.1］ μg/L, P <0.05), with no statistically significant differences between the two groups (P >0.05). At 24 weeks, however, the PSA levels in the control and trial groups were slightly increased to (23.1 ± 28.4) and (19.6 ± 23.5) μg/L, respectively, with no statistically significant differences in between (P >0.05). Karnofsky, FACT-P and TCM symptoms scores were all markedly improved in the trial group after 12 weeks of treatment (P <0.05) and remained stable at 24 weeks, but not in the control group either at 12 or at 24 weeks (P >0.05).. TCM Fuyang Huayu Prescription combined with endocrine therapy and chemotherapy is effective for CRPC.. 目的： 探讨中西医结合治疗去势抵抗性前列腺癌（CRPC）的疗效。方法： 54例CRPC患者随机均分为对照组和治疗组。对照组应用内分泌治疗（口服比卡鲁胺50 mg/d，每4周皮下注射戈舍瑞林3.6 mg ）+化疗（每3周静脉滴注多西他赛75 mg/m2+口服泼尼松5 mg，早晚各1次），治疗组在其基础上加用扶阳化瘀方每日1剂，分早晚服，疗程均为24周。观察两组患者治疗前、治疗12及24周后血清前列腺特异抗原（PSA）水平、体力状况（Karnosky评分）、生活质量（FACT-P）及中医症状评分的变化。结果： 治疗12周后，对照组与治疗组的血清PSA值分别由治疗前的(25.9±39.3) μg/L、(22.1±33.9) μg/L下降至(20.0±21.1) μg/L、(17.9±19.1) μg/L，两组较治疗前均有统计学差异（P<0.05），两组间相比无统计学差异（P>0.05）。治疗24周后，对照组与治疗组血清PSA较治疗3个月后分别小幅上升至(23.1±28.4) μg/L、(19.6±23.5) μg/L，但均无统计学差异（P>0.05）。治疗组在治疗12周后体力状况、生活质量、中医症状评分均得到改善，较治疗前均有统计学差异（P<0.05），治疗24周时较治疗12周时保持稳定；但对照组治疗12周、24周后体力状况、生活质量、中医症状评分均无明显改善（P>0.05）。结论： 扶阳益阴、解毒化瘀方联合化疗对CRPC具有一定的临床疗效，值得临床推广。.

Topics: Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Goserelin; Humans; Male; Nitriles; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Taxoids; Tosyl Compounds; Treatment Outcome

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

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

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

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

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

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

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

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

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

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

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 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

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

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

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

The current study was conducted to determine the effect of goserelin and bicalutamide on progression-free survival (PFS) in patients with epithelial ovarian cancer who were in second or greater complete disease remission.. Patients received bicalutamide at a dose of 50 mg orally daily and goserelin at a dose of 3.6 mg subcutaneously every 4 weeks. CA 125 was obtained monthly, with computed tomography performed every 3 months. Correlative studies included serum luteinizing hormone, follicle-stimulating hormone, vascular endothelial growth factor, free testosterone, and androstenedione and the germline polymorphisms CYP19A1 and androgen receptor.. Between October of 2000 and October of 2002, 35 patients were enrolled. Three patients (9%) received therapy at the time of first disease remission and were removed from the study, and 1 patient (3%) was removed for liver function test abnormalities. The most frequent toxicities were grade 1 alkaline phosphatase (54%), fatigue (57%), and hot flashes (42%) based on the National Cancer Institute common toxicity scale, version 2.0. The PFS for patients receiving protocol therapy in second disease remission (21 patients) was 11.4 months (95% confidence interval [95% CI], 10.2-12.6 months). The PFS for patients receiving protocol therapy in third or fourth disease remission (11 patients) was 11.9 months (95% CI, 10.8-14.1 months). The percentage of patients remaining in second disease remission at given times are: 100% at 3 months, 100% at 6 months, 72% at 9 months, 47% at 12 months, 28% at 15 months, 22% at 18 months, 19% at 21 months, and 13% at 24 months. There were no associations noted between androgen receptor repeat number, genotype, allelotype, or haplotypes and PFS.. The use of goserelin and bicalutamide did not appear to prolong PFS in patients with epithelial ovarian cancer in second or greater complete disease remission. The number of patients in disease remission at given time points may serve as a clinical trial endpoint for future studies of consolidation therapy.

Topics: Adult; Aged; Androgen Antagonists; Anilides; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Female; Goserelin; Humans; Middle Aged; Neoplasm Recurrence, Local; Nitriles; Ovarian Neoplasms; Tosyl Compounds

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

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 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

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

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

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 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 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

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

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 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

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 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

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

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

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

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

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

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

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

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

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

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

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

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

Topics: Aged, 80 and over; Androstenes; Anilides; Antibodies, Monoclonal, Humanized; Antigens, Surface; Brachytherapy; Disease Progression; Gallium Radioisotopes; Gene Expression Regulation, Neoplastic; Glutamate Carboxypeptidase II; Goserelin; Humans; Ligands; Male; Nitriles; Positron-Emission Tomography; Programmed Cell Death 1 Receptor; Prostatectomy; Prostatic Neoplasms, Castration-Resistant; Salvage Therapy; Tosyl Compounds

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

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

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 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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 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

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

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

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

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

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

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

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

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

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

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

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

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

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