leuprolide and Adenocarcinoma

Topics: Adenocarcinoma; Aged, 80 and over; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Fatal Outcome; Humans; Leuprolide; Lower Urinary Tract Symptoms; Male; Nitriles; Prostatectomy; Prostatic Neoplasms; Tosyl Compounds

A case of neuroendocrine (NE) differentiated prostate cancer is reported herein, which was progressed with NE differentiation during hormonal treatment in adenocarcinoma of the prostate. A 65-year-old man was admitted to our department with increased serum prostate specific antigen (PSA) (150 ng/ml). A prostate biopsy was performed and histological examinations indicated poorly differentiated adenocarcinoma with a Gleason score of 5 + 4 = 9. Further examinations showed metastases to systemic bones. The clinical stage was T3bN0M1b and hormonal therapy using leuprorelin was started. Eighteen months after hormonal therapy, the serum PSA level declined to 1.702 ng/ml. He subsequently experienced edema in his legs. Computed tomography (CT) demonstrated enlargement of the prostate and swelling of multiple pelvic lymph nodes. Immunohistochemical examination of a re-biopsy specimen revealed a neuroendocrine carcinoma. The neuron-specific enolase (NSE) level was 50.9 ng/ml. The treatment measure was changed from hormonal therapy to combination chemotherapy comprising cisplatin (CDDP) and irinotecan (CPT-11). Pelvic radiotherapy (50 Gy) was then performed. Two courses of the chemotherapy resulted in a great reduction of the tumor volume. However, he had liver metastases 3 months later. His condition worsened rapidly and he died at 8 months after definite diagnosis.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Cell Differentiation; Humans; Leuprolide; Male; Phosphopyruvate Hydratase; Prostate-Specific Antigen; Prostatic Neoplasms

Disseminated intravascular coagulation (DIC) is the most frequent coagulation disorder associated with metastatic prostate cancer. We report a case of a 60-year-old white man who was admitted in our department with ecchymoses and haematuria secondary to a DIC associated with metastatic prostate cancer. A review of this clinical scenario is also reported.

Topics: Adenocarcinoma; Anilides; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Diagnosis, Differential; Disseminated Intravascular Coagulation; Ecchymosis; Femur; Hematuria; Humans; Leuprolide; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome

The development of resistance to anticancer therapies is a major hurdle in preventing long-lasting clinical responses to conventional therapies in hormone-refractory prostate cancer. Herein, the molecular evidence documenting that bone metastasis microenvironment survival factors (mainly the paracrine growth hormone-independent, urokinase-type plasminogen activator-mediated increase of IGF-1 and the endocrine production of growth hormone-dependent IGF-1, mainly liver-derived IGF-1 production) produce an epigenetic form of prostate cancer cells that are resistant to proapoptotic therapies is reviewed. Consequently, the authors present the conceptual framework of a novel antibone microenvironment survival factor, mainly an anti-IGF-1 hormonal manipulation for androgen ablation refractory prostate cancer (a combination of conventional androgen ablation therapy [luteinising hormone-releasing hormone agonist-A or orchiectomy]) with dexamethasone plus somatostatin analogue, which yielded durable objective responses and major improvement of bone pain and performance status in stage D3 prostate cancer patients.

Topics: Adenocarcinoma; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Bone Neoplasms; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Dexamethasone; Drug Resistance, Neoplasm; Estramustine; Etoposide; Gonadotropin-Releasing Hormone; Growth Substances; Humans; Leuprolide; Male; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Orchiectomy; Osteoblasts; Osteoclasts; Paracrine Communication; Peptides, Cyclic; Prospective Studies; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Receptors, Androgen; Salvage Therapy; Somatostatin; Survival Analysis; Triptorelin Pamoate

S.R., a 65-year-old male with a history of prostate cancer, went to a cancer center in 2003. He had developed symptoms of bladder outlet obstruction in 1999 and was seen by a urologist. His baseline prostate-specific antigen (PSA) was 44 ng/ml. On physical examination, his prostate was enlarged, and a biopsy in January 2000 revealed adenocarcinoma with a Gleason score of 8. A metastatic workup, including a bone scan and a computed tomography scan of the abdomen and pelvis (CT A/P), was negative for evidence of metastatic disease. S.R. received conformal external beam radiation, and the luteinizing hormone-releasing hormone agonist leuprolide acetate was initiated. Following treatment, his PSA nadired to 0.2 ng/ml, and he did well until 2002, when his PSA started to rise. A reevaluation CT A/P revealed enlarged retroperitoneal and pelvic lymph nodes, and a bone scan was positive for metastatic disease. He underwent a bilateral orchiectomy in November 2002.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Combined Modality Therapy; Diphosphonates; Gonadotropin-Releasing Hormone; Humans; Imidazoles; Jaw Diseases; Leuprolide; Male; Orchiectomy; Osteonecrosis; Osteoporosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Conformal; Risk Factors; Tomography, X-Ray Computed; Zoledronic Acid

Despite significant progress in breast cancer treatment, mammary tumours still represent the second most frequent cause of cancer-related death in women in the US, with > 211,000 new cases in 2005; however, an expanding range of options for early diagnosis and more reliable risk assessment offers new alternatives for disease control by cancer prevention. Completed large studies with the classical selective estrogen receptor modulator (SERM) tamoxifen have demonstrated that preventing breast cancer pharmacologically is now possible. Novel SERMs, aromatase inhibitors and gonadotropin-releasing hormone agonists targeting hormonal pathways are being tested in clinical trials, revealing the potential for dramatic reductions in tumour incidence with minimal side effects; however, SERMs and aromatase inhibitors are effective only against estrogen receptor-positive tumours, thus chemopreventive drugs targeting other critical signalling pathways (such as retinoids, selective COX inhibitors and tyrosine kinase inhibitors) may provide a means to prevent estrogen receptor-negative breast cancer. In the future, hormonal and estrogen receptor-independent agents may be combined to prevent the development of all mammary tumours. This article reviews the current and novel strategies for breast cancer prevention.

Topics: Adenocarcinoma; Adult; Aged; Animals; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Clinical Trials as Topic; Cyclooxygenase 2 Inhibitors; Double-Blind Method; Drug Evaluation, Preclinical; Drug Therapy, Combination; Estrogen Receptor Modulators; Estrogens; Female; Forecasting; Humans; Leuprolide; Mammary Neoplasms, Experimental; Mice; Middle Aged; Ovariectomy; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Raloxifene Hydrochloride; Randomized Controlled Trials as Topic; Rats; Retinoids; Selective Estrogen Receptor Modulators; Tamoxifen

To evaluate the approach to management of localized prostate cancer (PCa) in patients with human immunodeficiency virus (HIV) in the highly active antiretroviral therapy era.. A retrospective analysis was performed on 10 HIV-positive patients who recently presented with elevated prostate-specific antigen levels and clinically localized PCa.. At the diagnosis of PCa, the average patient was 54.0 years old, had been HIV positive for 8.75 years, had a CD4 count of 417, a prostate-specific antigen level of 9.2 ng/mL, and a Gleason score of 6. Eight of the patients had risk factors for PCa--either African-American descent (n = 6) or a positive family history (n = 2). The treatment was laparoscopic radical prostatectomy in 1, potency-preserving androgen deprivation in 1, cryosurgery in 1, brachytherapy in 2, observation in 2, and external beam radiotherapy in 3.. Screening of all HIV-positive men should be initiated at age 40 if they have either a positive family history of prostate cancer or are of African-American descent. Asymptomatic HIV-positive patients should be offered all therapeutic PCa treatment options.

Topics: Adenocarcinoma; Adult; Aged; Anilides; Antineoplastic Agents, Hormonal; Antiretroviral Therapy, Highly Active; Biomarkers, Tumor; Brachytherapy; Case Management; Combined Modality Therapy; Cryosurgery; Finasteride; Follow-Up Studies; HIV Infections; Humans; Leuprolide; Life Expectancy; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Proteins; Nitriles; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy, High-Energy; Retrospective Studies; Tosyl Compounds

An 88-year-old patient with a poorly differentiated adenocarcinoma of the prostate gland was found to have all cardinal findings of syndrome of inappropriate antidiuretic hormone secretion (SIADH). Elevated levels of antidiuretic hormone were found in the patient's serum and in the prostatic tumor and the cytoplasms of the tumor was positive for prostate specific antigen and was faintly positive for antidiuretic hormone (ADH). He responded well to combination therapy of androgen blockade with leuprorelin acetate and flutamide, and laboratory findings of SIADH and serum ADH level returned to normal. However, he died of sudden profuse bleeding caused by gastric ulcers 6 months after the therapy. Ten cases of SIADH caused by prostatic cancer have been reported including the present case.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Humans; Inappropriate ADH Syndrome; Leuprolide; Male; Paraneoplastic Endocrine Syndromes; Prostatic Neoplasms; Treatment Outcome; Vasopressins

A 72-year-old male treated with flutamide for metastatic prostate cancer developed lethargy and confusion. He was noted to be icteric and his liver enzymes were elevated. Within a week of discontinuing the medication, the patient's mental status and liver function returned to normal. Although flutamide-induced near fatal liver dysfunction has been described, progression to encephalopathy is a rare occurrence. Based on a review of the literature, management guidelines for the use of flutamide are suggested.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Drug Therapy, Combination; Flutamide; Hepatic Encephalopathy; Humans; Leuprolide; Male; Prostatic Neoplasms

We report the syndrome of inappropriate antidiuretic hormone secretion in a 59-year-old man with stage C adenocarcinoma of the prostate. Serum antidiuretic hormone levels returned to normal following treatment with a gonadotropin-releasing hormone analogue. To our knowledge this case represents the first in which resolution of this syndrome occurred with treatment of the carcinoma.

Topics: Adenocarcinoma; Humans; Inappropriate ADH Syndrome; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Remission Induction

Endometrioid carcinoma of the prostate is an uncommon form of prostatic cancer. The authors present the case of a 77 year-old man and discuss the different particularities of this rare entity.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Flutamide; Humans; Leuprolide; Male; Prostatic Neoplasms

Luteinizing hormone-releasing hormone agonist therapy for prostate cancer is a new method of management for metastatic disease. During the initial 1 to 2-week period of administration an increase in serum testosterone concentration can lead to an exacerbation of clinical symptoms (flare phenomenon). Two patients are summarized who received luteinizing hormone-releasing hormone agonist therapy without flare blockade and died suddenly during month 1 of therapy. A review of 765 patients in 9 series found 10.9% who suffered disease flare and 15 who died during disease flare. Of these 17 patients 12 were similar to our 2. These data suggest that any patient placed on luteinizing hormone-releasing hormone agonist therapy for prostate cancer merits some form of flare blockade during the initial 1 or 2 months of therapy.

Topics: Adenocarcinoma; Antineoplastic Agents; Death, Sudden; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Time Factors

Combined therapy, the treatment of advanced adenocarcinoma of the prostate by total androgen suppression, is still a controversial subject today. Some studies performed during the 1980s support the value of this therapeutic approach, while others have found it to be no more effective than surgical or chemical castration alone. Recently, the results of a randomized, controlled, multicenter intergroup study of combined therapy sponsored by the U.S. National Cancer Institute (NCI) became available. These results suggest that combined therapy offers some advantages over monotherapy in the treatment of advanced prostate cancer. A variety of drugs are available to suppress adrenal androgens. However, the value of these agents in prostate cancer therapy continues to be hotly debated.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents; Combined Modality Therapy; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic

Topics: Adenocarcinoma; Animals; Disease Models, Animal; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Male; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testis; Testosterone

Injectable luteinizing hormone-releasing hormone agonists (e.g., leuprolide) are the standard agents for achieving androgen deprivation for prostate cancer despite the initial testosterone surge and delay in therapeutic effect. The efficacy and safety of relugolix, an oral gonadotropin-releasing hormone antagonist, as compared with those of leuprolide are not known.. In this phase 3 trial, we randomly assigned patients with advanced prostate cancer, in a 2:1 ratio, to receive relugolix (120 mg orally once daily) or leuprolide (injections every 3 months) for 48 weeks. The primary end point was sustained testosterone suppression to castrate levels (<50 ng per deciliter) through 48 weeks. Secondary end points included noninferiority with respect to the primary end point, castrate levels of testosterone on day 4, and profound castrate levels (<20 ng per deciliter) on day 15. Testosterone recovery was evaluated in a subgroup of patients.. A total of 622 patients received relugolix and 308 received leuprolide. Of men who received relugolix, 96.7% (95% confidence interval [CI], 94.9 to 97.9) maintained castration through 48 weeks, as compared with 88.8% (95% CI, 84.6 to 91.8) of men receiving leuprolide. The difference of 7.9 percentage points (95% CI, 4.1 to 11.8) showed noninferiority and superiority of relugolix (P<0.001 for superiority). All other key secondary end points showed superiority of relugolix over leuprolide (P<0.001). The percentage of patients with castrate levels of testosterone on day 4 was 56.0% with relugolix and 0% with leuprolide. In the subgroup of 184 patients followed for testosterone recovery, the mean testosterone levels 90 days after treatment discontinuation were 288.4 ng per deciliter in the relugolix group and 58.6 ng per deciliter in the leuprolide group. Among all the patients, the incidence of major adverse cardiovascular events was 2.9% in the relugolix group and 6.2% in the leuprolide group (hazard ratio, 0.46; 95% CI, 0.24 to 0.88).. In this trial involving men with advanced prostate cancer, relugolix achieved rapid, sustained suppression of testosterone levels that was superior to that with leuprolide, with a 54% lower risk of major adverse cardiovascular events. (Funded by Myovant Sciences; HERO ClinicalTrials.gov number, NCT03085095.).

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Male; Middle Aged; Phenylurea Compounds; Prostatic Neoplasms; Pyrimidinones; Testosterone

Patients with locally advanced prostate cancer have an increased risk of cancer recurrence and mortality. In this phase II trial, we evaluate neoadjuvant enzalutamide and leuprolide (EL) with or without abiraterone and prednisone (ELAP) before radical prostatectomy (RP) in men with locally advanced prostate cancer.. Eligible patients had a biopsy Gleason score of 4 + 3 = 7 or greater, prostate-specific antigen (PSA) greater than 20 ng/mL, or T3 disease (by prostate magnetic resonance imaging). Lymph nodes were required to be smaller than 20 mm. Patients were randomly assigned 2:1 to ELAP or EL for 24 weeks followed by RP. All specimens underwent central pathology review. The primary end point was pathologic complete response or minimal residual disease (residual tumor ≤ 5 mm). Secondary end points were PSA, surgical staging, positive margins, and safety. Biomarkers associated with pathologic outcomes were explored.. Seventy-five patients were enrolled at four centers. Most patients had high-risk disease by National Comprehensive Cancer Network criteria (n = 65; 87%). The pathologic complete response or minimal residual disease rate was 30% (n = 15 of 50) in ELAP-treated patients and 16% (n = four of 25) in EL-treated patients (two-sided P = .263). Rates of ypT3 disease, positive margins, and positive lymph nodes were similar between arms. Treatment was well-tolerated. Residual tumors in the two arms showed comparable levels of ERG, PTEN, androgen receptor PSA, and glucocorticoid receptor expression. Tumor ERG positivity and PTEN loss were associated with more extensive residual tumors at RP.. Neoadjuvant hormone therapy followed by RP in locally advanced prostate cancer resulted in favorable pathologic responses in some patients, with a trend toward improved pathologic outcomes with ELAP. Longer follow-up is necessary to evaluate the impact of therapy on recurrence rates. The potential association of ERG and PTEN alterations with worse outcomes warrants additional investigation.

Topics: Adenocarcinoma; Adult; Aged; Androgen Antagonists; Androstenes; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Chemotherapy, Adjuvant; Humans; Kallikreins; Leuprolide; Magnetic Resonance Imaging; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm, Residual; Nitriles; Phenylthiohydantoin; Prednisone; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Time Factors; Treatment Outcome; United States

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

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

To evaluate for a possible testosterone surge during transition of therapy from degarelix to leuprolide.. We conducted an investigator-initiated, prospective, single-arm, open-label trial for evaluation of a potential testosterone surge during a transition of therapy from degarelix to leuprolide. Study patients were administered 3 monthly depot injections of degarelix, followed by one 3-month depot injection of leuprolide. A rise in serum testosterone was considered clinically relevant in previously castrate patients whose testosterone rose above 50 ng/dL.. Forty-five patients aged 59-86 years were included in the final analysis after completing the entire 6-month study. Nineteen percent of patients had received prior androgen deprivation therapy, and 10% had metastatic disease. Mean serum testosterone was reduced from a baseline of 374.6 ± 155.7 ng/dL to 16.5 ± 8.1 ng/dL, and prostate-specific antigen reduced from 23.8 ± 55.8 ng/mL to 1.6 ± 3.7 ng/mL after 3 months of treatment with degarelix. On transition from degarelix to leuprolide (day 90), there was a rise in testosterone from the nadir of 16.5 ng/dL to a peak of 25.8 ng/dL (P = .0005), occurring at day 93. Four patients (8.9%) experienced a testosterone surge with a mean peak serum testosterone of 80.7 ng/dL; all 4 returned to castrate levels within 7 days, and all remained asymptomatic throughout the testosterone fluctuation.. Fluctuations in serum testosterone after this transition of therapy were mild and short-lived with only 8.9% of men experiencing testosterone elevations to noncastrate levels.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Oligopeptides; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

To identify the factors underlying prostate cancer (PCa) patients' depression-anxiety, sexual problems, urinary dysfunction and androgen deprivation therapy (ADT)-linked breast changes and hot flushes, and test these as predictors of loss of masculinity (LoM) over 36 months following diagnosis.. One thousand seventy patients from the TROG 03.04 (RADAR) trial the EORTC QLQ C-30 and PR 25 questionnaires, and the International Prostate Cancer Symptom Score of the American Urological Association at baseline, 3, 7, 12, 18, 24 and 36 months. Selected items from these scales were factor-analysed to identify a four-component solution for responses at 18 and 36 months, and these components were regressed against a single-item measuring LoM.. Depression-anxiety factor was the most powerful predictor of LoM at both time points, followed by sexual problems of ADT side effects (breast changes and hot flushes). Urinary dysfunction was not a consistent predictor of LoM. Depression-anxiety was also the most significant factor distinguishing between those men who reported LoM and those who did not.. Although LoM is often reported as arising from ADT, the relative power of depression-anxiety in predicting LoM, both at the selected time points and using a time-lagged analysis, plus the finding that depression-anxiety was the most consistent difference between men who reported LoM and those who did not, argues for the presence of adverse mood states as being the key ingredient in deciding if PCa patients experience loss of their feelings of masculinity.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Anxiety; Depression; Hot Flashes; Humans; Leuprolide; Male; Masculinity; Middle Aged; Prostatic Neoplasms; Sexual Dysfunction, Physiological; Surveys and Questionnaires

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

Long-term hormonal ablation in prostate cancer is associated with decreased overall health and quality of life. Few reports emphasized the role of chemotherapy in the management of early stage prostate cancer. This study analyzed the safety and efficacy of androgen deprivation therapy (ADT) plus chemotherapy as initial treatment for patients identified as local failures or not eligible for prostatectomy or radiation therapy due to advanced disease presentation.. Enrolled patients received ADT in the form of leuprolide every 12 weeks for 24 months with bicalutamide initiating after the completion of chemotherapy. Chemotherapy consisted of ketoconazole and doxorubicin for weeks 1, 3, and 5 and estramustine and docetaxel and for weeks 2, 4 and 6. During weeks 7 and 8, no treatment was received.. Forty-six patients were enrolled, and forty-five patients were evaluable. Median progression-free survival (PFS) was 23.4 months. Median overall survival (OS) was 53.7 months. Out of 45 patients with measurable disease, 22 patients had an objective response: 9 patients achieved a complete response; 2 patients achieved a partial response; 10 patients achieved stable disease. Frequent grade 3 adverse events included elevated ALT (17 %), hypokalemia (13 %), and hypophosphatemia (13 %). Grade 4 adverse events were rare and included low bicarbonate (2 %), hypokalemia (2 %), leukocytopenia (2 %), and neutropenia (2 %).. The treatment demonstrated clinical benefit in all patient subsets with minimal reversible treatment-related adverse events. Subgroup analysis suggests that having prior local therapy resulted in greater PFS and OS.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Humans; Kallikreins; Leuprolide; Male; Middle Aged; Neoplasm Grading; Nitriles; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy; Tosyl Compounds; Treatment Failure

In this article, we present the results of organ-preserving treatment applied in 24 patients of reproductive age with atypical endometrial hyperplasia or early-stage endometrial cancer. All of them would like to preserve their reproductive potential. Thirteen women with atypical endometrial hyperplasia were treated with the combination of six intramuscular injections of 3.75 mg gonadotropin-releasing hormone agonist (GnRHa)--leuproreline acetate depot every 4 weeks. After the third injection of 3.75 mg of leuproreline acetate, the levonorgestrel intrauterine hormonal system containing 52 mg levonorgestrel (Mirena®, Bayer, Germany) was inserted for at least 6 months. In 11 women with stage IA well-differentiated endometrial adenocarcinoma, hormonal therapy included nine intramuscular injections of 3.75 mg of GnRHa every 4 weeks. After the third injection of 3.75 mg of GnRHa, we also inserted a GnRH-IUS (Mirena®) for at least 12 months. This type of therapy was effective for all these patients and may be offered to be used as an alternative to surgery in women with atypical endometrial hyperplasia or early stage 1A well-differentiated endometrial cancer in women of reproductive age. Three women with endometrial cancer became pregnant and two of them delivered at term and one has an ongoing pregnancy.

Topics: Adenocarcinoma; Administration, Intravaginal; Adult; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Drug Delivery Systems; Drug Therapy, Combination; Endometrial Hyperplasia; Endometrial Neoplasms; Female; Gonadotropin-Releasing Hormone; Humans; Injections, Intramuscular; Leuprolide; Levonorgestrel; Neoplasm Staging; Organ Sparing Treatments; Pilot Projects; Progestins; Young Adult

Radiotherapy combined with androgen-deprivation therapy (ADT) is superior to radiotherapy alone in localised prostate cancer; however, data comparing ADT alone are somewhat limited.. To compare 3-yr ADT plus radiotherapy with ADT alone in locally advanced prostate cancer patients.. A multicentre randomised open controlled phase 3 trial in 264 histologically confirmed T3-4 or pT3N0M0 prostate cancer patients randomised from March 2000 to December 2003.. ADT (11.25mg subcutaneous depot injection of leuprorelin every 3 mo for 3 yr) plus external-beam radiotherapy or ADT alone. Flutamide (750 g/d) was administered for 1 mo.. The primary objective was 5 yr progression-free survival (PFS) according to clinical or biologic criteria, using the American Society for Therapeutic Radiology and Oncology (ASTRO) and the newer (Phoenix) definition (nadir plus 2 ng/ml), by intention to treat. Secondary objectives included time to locoregional recurrence and distant metastases, and overall and disease-specific survival. Our Analyses: intent-to-treat analysis, multivariate analyses using a Cox model with a 5% threshold from univariate analysis, and Kaplan-Meier estimates.. ADT alone was administered to 130 patients and combined therapy to 133. With a median follow-up of 67 mo, 5-yr PFS was 60.9% for combined therapy versus 8.5% with ADT alone (ASTRO; p<0.0001), and 64.7% versus 15.4%, respectively, for Phoenix (p<0.0011). Locoregional progression was reported in 9.8% of combined-therapy patients versus 29.2% with ADT alone (p<0.0001) and metastatic progression in 3.0% versus 10.8%, respectively (p<0.018). Overall survival was 71.4% with combined therapy versus 71.5% with ADT alone; disease-specific survival was 93.2% versus 86.2%. Limitations included the relatively small population and a relatively short follow-up period.. Combined therapy strongly favoured improved PFS, locoregional control, and metastasis-free survival. Longer follow-up is needed to assess the potential survival impact.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemoradiotherapy; Disease-Free Survival; Drug Therapy, Combination; Flutamide; Humans; Leuprolide; Male; Middle Aged; Neoplasm Grading; Prostate-Specific Antigen; Prostatic Neoplasms

Adjuvant androgen suppression and bisphosphonates with escalating doses of radiotherapy might improve efficacy outcomes in men with locally advanced prostate cancer. In this study, we investigated whether these treatments had a detrimental effect on patient-reported-outcome (PRO) scores.. We undertook a phase 3 trial with a 2×2 factorial design in 23 centres in Australia and New Zealand in men with non-metastatic adenocarcinoma of the prostate (stage T2b-4 or T2a, Gleason score ≥7, and baseline prostate-specific antigen concentration [PSA] ≥10 μg/L), and without previous lymph node or systemic metastases or comorbidities that could reduce life expectancy to less than 5 years. The men were randomly assigned in a 1:1:1:1 ratio to 6 months of neoadjuvant (short-term) androgen suppression (STAS) with leuprorelin (22·5 mg every 3 months, intramuscularly) or an additional 12 months (intermediate-term androgen suppression [ITAS]) of leuprorelin with or without 18 months of zoledronic acid (4 mg every 3 months, intravenously). Study drug administration commenced at randomisation after which radiotherapy started within the fifth month in all groups. Treatment allocation was open-label, and computer-generated randomisation, stratified by centre, baseline concentrations of PSA, clinical stage of the tumour, Gleason score, and use of a brachytherapy boost, was done by use of the minimisation technique. PRO scores were calculated from European Organization for Research and Treatment of Cancer quality-of-life and prostate-specific quality-of-life module questionnaires and compared with multiple regression models at baseline, and end of radiotherapy, and 18 months and 36 months according to group and radiation dose. The trial is ongoing and the primary endpoint, prostate-cancer-specific mortality, will be reported in 2014. This study is the final report of PRO scores (a secondary endpoint). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00193856.. 1071 men were randomly assigned to STAS (n=268), STAS plus zoledronic acid (n=268), ITAS (n=268), and ITAS plus zoledronic acid (n=267). At the end of radiotherapy, significant detrimental changes in PRO scores (p<0·01) occurred in all groups. There were no significant differences in global health status between groups at any timepoint. At 18 months, PROs that were significantly worse in the ITAS groups when compared with STAS were hormone-treatment-related symptoms (HTRS; STAS, 10·20 [95% CI 8·66-11·75]; ITAS, 17·36 [13·63-21·08], p<0·01; and ITAS plus zoledronic acid, 19·14 [15·43-22·85], p<0·01), sexual activity (STAS, 26·38 [23·50-29·27]; ITAS, 14·40 [7·44-21·36], p<0·01; and ITAS plus zoledronic acid, 16·34 [9·39-23·28], p<0·01), social function (STAS, 90·31 [87·89-92·73]; ITAS, 87·35 [81·52-93·18], p=0·09; and ITAS plus zoledronic acid, 83·66 [77·85-89·48], p<0·01), fatigue (STAS, 17·05 [14·58-19·51]; ITAS 24·52 [18·58-30·46], p<0·01; and ITAS plus zoledronic acid, 24·26 [18·33-30·18], p<0·01), and financial problems (STAS, 3·39 [1·29-5·48]; ITAS, 8·97 [3·92-14·02], p<0·01; and ITAS plus zoledronic acid, 8·92 [3·89-13·96], p<0·01). With the exception of HTRS, in which marginal differences remained, persisting significant differences disappeared by 36 months. Other factors associated with significant detrimental changes in PRO scores were a brachytherapy boost, incomplete testosterone and haemoglobin recoveries, age, and smoking.. Compared with 6 months of androgen suppression, 18 months of androgen suppression causes additional detrimental changes at the 18 month follow-up in some PRO scores but not in global quality-of-life scores. However, with the exception of HTRS, these differences resolved by 36 months. The use of zoledronic acid every 3 months over 18 months does not result in additional detrimental changes, but the use of a brachytherapy boost to achieve radiation dose escalation in the prostate can adversely affect emotional function and financial problems.. National Health and Medical Research Council of Australia, Novartis Pharmaceuticals Australia, Abbott Pharmaceuticals Australia, New Zealand Health Research Council, New Zealand Cancer Society, University of Newcastle (Australia), Hunter Medical Research Institute, Calvary Mater Radiation Oncology Fund, and Maitland Cancer Appeal.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Brachytherapy; Diphosphonates; Humans; Imidazoles; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Prostatic Neoplasms; Quality of Life; Radiotherapy Dosage; Zoledronic Acid

To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients.. Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of > or =T3a or an initial prostate-specific antigen [PSA] level of > or =20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales.. All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity.. Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Combined Modality Therapy; Dose Fractionation, Radiation; Gastrointestinal Tract; Humans; Leuprolide; Lymphatic Irradiation; Male; Middle Aged; Pelvis; Prospective Studies; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radiation Injuries; Radiotherapy, Intensity-Modulated; Rectum; Seminal Vesicles; Urinary Bladder; Urogenital System

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

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

To evaluate the efficacy and safety of degarelix, a new gonadotrophin-releasing hormone (GnRH) antagonist (blocker), vs leuprolide for achieving and maintaining testosterone suppression in a 1-year phase III trial involving patients with prostate cancer.. In all, 610 patients with adenocarcinoma of the prostate (any stage; median age 72 years; median testosterone 3.93 ng/mL, median prostate-specific antigen, PSA, level 19.0 ng/mL) were randomized and received study treatment. Androgen-deprivation therapy was indicated (neoadjuvant hormonal treatment was excluded) according to the investigator's assessment. Three dosing regimens were evaluated: a starting dose of 240 mg of degarelix subcutaneous (s.c.) for 1 month, followed by s.c. maintenance doses of 80 mg or 160 mg monthly, or intramuscular (i.m.) leuprolide doses of 7.5 mg monthly. Therapy was maintained for the 12-month study. Both the intent-to-treat (ITT) and per protocol populations were analysed.. The primary endpoint of the trial was suppression of testosterone to

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Oligopeptides; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Outcome

To evaluate the toxicity and efficacy of individualized neoadjuvant androgen deprivation (AD) to maximal response followed by external beam radiotherapy (RT) with continued AD for a total of 9 months in a prospective phase II trial.. One hundred twenty-three patients received a total of 9 months of flutamide and luprolide combined with RT. RT initiation was individualized to begin after maximum response to AD as assessed by monthly digital rectal examination and prostate-specific antigen (PSA). The neoadjuvant phase was restricted to no more than 6 months.. Median time to initiation of RT was 4.7 months. Indications to begin RT (and their rates) were undetectable PSA (28%), PSA unchanged from one month to the next (46%), PSA rising from one month to the next (10%), 6 months of AD (14%), and other (2%). Five-year outcomes were biochemical disease-free survival, (DFS) 63% +/- 7%; clinical DFS, 75% +/- 5%; cancer-specific survival, 99% +/- 1%; and overall survival, 89% +/- 3%. Patients initiating RT after 6 months of AD had significantly lower biochemical and clinical DFS. Those patients whose testosterone recovered to normal after completion of AD had a significantly superior survival rate. Of those patients potent before treatment, 65% remained so at last follow-up.. The combination of 9 months of AD and RT, with initiation of RT individualized on the basis of maximum response to AD, achieves disease control rates comparable with past studies, while preserving potency in many patients. Further studies are warranted to determine the optimal combination of AD and RT in this patient population.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease-Free Survival; Flutamide; Humans; Leuprolide; Male; Neoadjuvant Therapy; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy; Risk; Time Factors; Treatment Outcome

To assess the early histological effects of pharmacological androgen deprivation (AD), which have been assessed only over longer periods, as surgical castration leads rapidly to diminished cell proliferation and enhanced cell death within the prostate.. With Institutional Review Board approval, 35 patients were randomly assigned (seven in each group) to receive 0, 7, 14, 21 and 28 days of AD (flutamide, 250 mg orally three times/day, and one injection with leuprolide acetate 7.5 mg) before radical prostatectomy. The surgical specimens were assessed by conventional histology and immunohistochemistry, while macroarray analysis and quantitative real-time polymerase chain reaction (QRT-PCR) were used to examine gene expression.. There were morphological changes within the prostatic tissues as early as 7 days after initiating AD, similar to the response to castration. There was tumour cell vacuolization indicating cellular injury, glandular atrophy and mononuclear cell infiltration as prominent and progressive effects but, by contrast with castration studies, there were no changes in epithelial proliferation or apoptosis. Macroarray analysis, validated by QRT-PCR and immunohistochemistry, showed up-regulation of numerous and potentially counter-effective genes involved in the cell cycle and apoptosis.. Pharmacological AD induces significant involution within prostatic tissues over 7-28 days, but allows the persistence of some viable tumour cells capable of proliferation.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Flutamide; Humans; Leuprolide; Male; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Biochemical results from a prospective Phase II trial of intermittent androgen suppression for recurrent prostate cancer after radiotherapy were analyzed for correlations to the onset of hormone-refractory disease.. Patients with histologically confirmed adenocarcinoma of the prostate and a rising serum prostate-specific antigen (PSA) level after external beam irradiation of the prostate were treated intermittently with a 36-week course of cyproterone acetate and leuprolide acetate. Then, patients were stratified according to their serum PSA range at the start of each cycle and were followed with further biochemical testing until disease progression was evident.. The mean PSA reduction was 95.2% irrespective of stratification group. A baseline serum PSA level <10 microg/L and a serum PSA nadir or=7.5 nmol/L was observed in 75%, 50%, 40%, and 30% of men in Cycles 1 to 4, respectively, and was sufficient to normalize the level of hemoglobin in each cycle, which dropped by an average of 10.8 g/L during treatment (P < .0001).. The length of the off-treatment interval during cyclic androgen withdrawal therapy was related inversely to baseline and nadir levels of serum PSA. Nadir PSA was a powerful predictor of early progression to androgen independence.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cyproterone Acetate; Humans; Leuprolide; Male; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy; Testosterone

The safety, efficacy and pharmacokinetics of LA-2585, a new 6-month subcutaneous depot of leuprolide acetate (Atrix Laboratories, Fort Collins, Colorado) were investigated in patients with prostate cancer.. In this 12-month, open label, multicenter study 111 patients with adenocarcinoma of the prostate were administered 45.0 mg LA-2585 subcutaneously once every 6 months. The primary efficacy parameter was serum testosterone 50 ng/dl or less. Leuprolide acetate pharmacokinetics were analyzed in a subset of 28 patients.. Of the 111 enrolled patients 103 (93%) completed the 12-month study. Eight patients withdrew due to nonmedical reasons in 1, disease progression in 5 and cardiovascular disease in 2. By day 28, 108 of the 109 remaining patients (99%) achieved testosterone suppression, while 1 who never attained suppression was withdrawn at day 85. Mean time to castrate suppression was 21.2 days (median 21). At study completion 102 of 103 patients (99%) were below medical castrate testosterone levels of 50 ng/dl (mean +/- SE 12.3 +/- 2.1 ng/dl) with 91 of 103 (88%) at less than 20 ng/dl. Mean luteinizing hormone decreased from 6.98 +/- 0.48 mIU/ml at baseline to 0.23 +/- 0.14 mIU/ml at month 12. Luteinizing hormone was consistently below 1 mIU/ml. Mean prostate specific antigen decreased 97% from 39.8 +/- 21.5 ng/ml at baseline to 1.2 +/- 0.3 ng/ml at 12 months. No clinically significant flare reactions were observed. The most common treatment related adverse event was mild to moderate hot flashes.. LA-2585 (45.0 mg depot) consistently produced and maintained safe and effective serum testosterone suppression with total serum testosterone well below the medical castrate level of less than 50 ng/dl.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Drug Delivery Systems; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Subcutaneous Tissue; Time Factors

To clarify the optimal duration and methods for adjuvant endocrine therapy after external beam radiation therapy (EBRT) in patients with locally advanced prostate cancer.. Between 2001 and 2003, 215 patients with locally advanced prostate cancer were enrolled in the study. Patients were registered as primary candidates of the study and were treated with 6 months of LHRH agonist, with short-term of antiandrogen treatment for flare-up prevention. Patients with PSA levels below 10 ng/ml after the 6-month endocrine treatment were randomly divided into two arms. Then, a total dose of 72 Gy was given to the prostate. After 14 months of the protocol treatment, patients were treated with continuous androgen ablation (arm 1) or intermittent androgen ablation (arm 2).. A total of 188 cases (87%) remained in the protocol. The median PSA level at entry was 25.3 ng/ml. The Gleason score was 2-6 in 32 cases (16%), 7 in 94 cases (48%), and 8-10 in 68 cases (35%). The median PSA level showed a remarkable decrease to 1.1, 0.2, and 0.1 ng/ml, after 6, 8, and 14 months of the protocol treatment, respectively. Of the 157 cases treated with EBRT, 153 cases (97.5%) had no biochemical failure in the mean follow-up of 17.3 months.. The present study may reveal the possibilities of intermittent endocrine therapy after EBRT. However, the follow-up interval is short and little can be said about the results observed so far, exception of acute tolerance and patient acceptance of the protocol.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Brachytherapy; Chlormadinone Acetate; Combined Modality Therapy; Disease-Free Survival; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Treatment Outcome

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

To assess the effect of neoadjuvant hormone treatment before radical prostatectomy on: tumor/prostate volume, prostate-specific antigen (PSA) and testosterone levels, surgical margin status and tumor stage, and the ease of surgery following treatment.. Patients with clinically localized prostatic carcinoma were randomized to receive leuprolide acetate depot 3.75 mg once a month for 3 months and cyproterone acetate 300 mg once a week for 3 weeks prior to surgery (group A). A control group of patients had surgery without any pretreatment (group B).. 167 patients were evaluated for the efficacy parameters. In group A, 31% of patients had a reduction in tumor/prostate volume following hormone therapy. PSA and testosterone levels were significantly reduced (p = 0.0001) in patients in group A compared to basal values. Centralized histopathological data evaluated in 145 patients (group A and 75 group B) showed that more patients in group B had tumors at stages T3A and T3B than in group A; this difference was close to significance (p = 0.057). Positive surgical margins were more common in group B (60% of patients) compared to group A (39% of patients). Similarly lymph node involvement was more common in group B compared to group A (11 versus 3%). There was little difference between the 2 study groups for the other surgical parameters assessed (ease of dissection, duration of surgery, blood loss).. Neoadjuvant hormone therapy before radical prostatectomy has some effects in the treatment of prostate cancer. However, long-term follow-up of patients is needed to assess the impact of this therapy on morbidity and mortality.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Cyproterone Acetate; Delayed-Action Preparations; Humans; Leuprolide; Male; Middle Aged; Preoperative Care; Prostatectomy; Prostatic Neoplasms

To clarify the effect of intermittent androgen suppression on the time to androgen-independent progression and changes in quality of life (QOL).. Patients with locally advanced or metastatic prostate cancer were treated with a combination of leuprolide acetate and flutamide for 36 weeks. When the serum prostate-specific antigen (PSA) levels at 24 and 32 weeks were less than 4.0 ng/mL, treatment was withheld until the PSA level reached 15 ng/mL or the pretreatment level. This cycle of on-treatment and off-treatment was repeated until PSA failure (three consecutive increases in PSA level greater than 4.0 ng/mL during the on-treatment period) or symptomatic progression was observed. Changes in QOL were assessed by a self-assessment questionnaire.. Forty-nine patients (26 with T3N0M0, 8 with T2-T3N1M0, 2 with T4N0M0, and 13 with T2-T3N0M1) were enrolled. The mean follow-up period was 136.5 weeks. Thirty-one patients finished cycle 1, six finished cycle 2, and three finished cycle 3. The mean off-treatment duration in cycles 1, 2, and 3 was 46.1, 36.9, and 23.3 weeks, respectively. In the off-treatment period, statistically significant improvements in the QOL score were observed in the categories of potency (11.4 versus 2.4) and social/family well-being (20.3 versus 16.1) compared with those in the on-treatment period. PSA failure occurred in 6 patients (3 with T3N0M0 and 3 with T2-T3N1M0), and all patients were alive at last follow-up.. Our interim analysis indicated that QOL is remarkably improved during the off-treatment period. Intermittent androgen suppression would be a viable option for treatment of advanced prostate cancer, although a randomized controlled study is required to determine whether intermittent androgen suppression prolongs the time to androgen-independent cancer. We will continue follow-up in this study to a minimum of 3 years.

Topics: Adenocarcinoma; Aged; Androgens; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Disease Progression; Drug Administration Schedule; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Pilot Projects; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Surveys and Questionnaires; Testosterone; Treatment Failure

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

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

Patients with clinical T3 or T4 prostate cancer or with elevated serum prostate-specific antigen (PSA) levels greater than 40 ng/ml are at high risk of failure with primary treatment. Chemotherapy administered at the time of diagnosis may decrease the risk of recurrence. Patients with high risk localized prostate cancer were treated with two cycles of liposomal doxorubicin (Doxil) at 50 mg/m2 every 28 days. Patients were assessed for response by digital rectal examination (DRE), PSA, and endorectal magnetic resonance imaging (MRI) (erMRI). Patients were then treated with androgen ablative therapy and prostate radiotherapy. Seven patients were treated. Three patients had T3 disease, and 4 patients had T2b disease with either PSA greater than 40 ng/ml or erMRI evidence of seminal vesicle involvement or extracapsular disease. Median PSA was 29.4 ng/ml. None of the seven patients experienced a significant response, as measured by changes in DRE, PSA, or erMRI. Toxicity was significant, with 4 of 7 patients developing skin toxicity. All seven patients responded to androgen ablative therapy and prostate irradiation. Neoadjuvant liposomal doxorubicin demonstrates no apparent activity and significant toxicity. New strategies are needed to improve outcomes in high-risk prostate cancer.

Topics: Adenocarcinoma; Androgen Antagonists; Anilides; Antibiotics, Antineoplastic; Antineoplastic Agents, Hormonal; Doxorubicin; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Middle Aged; Neoadjuvant Therapy; Nitriles; Pilot Projects; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds

The safety, efficacy and pharmacokinetics of a unique 3-month subcutaneous depot of leuprolide acetate were investigated in patients with prostate cancer.. This open label, noncomparative, 6-month multicenter study enrolled 117 patients diagnosed with adenocarcinoma of the prostate. LA-2550 (22.5 mg. depot) (Atrix Laboratories, Fort Collins, Colorado) was administered subcutaneously once every 3 months. The primary efficacy parameter was serum testosterone 50 ng./dl. or less. Pharmacokinetics were analyzed in a subset of 22 patients.. Of the 117 enrolled patients 111 (98%) completed the 6-month study. Five patients withdrew for nontreatment related events and 1 was withdrawn because he received less than a full dose of the study drug. By day 28, 98% of patients had serum testosterone 50 ng./dl. or less and 84% had achieved 20 ng./dl. or less. By day 35 all patients had 50 ng./dl. or less testosterone. A patient with a breakthrough response after testosterone suppression on day 49 (112 ng./dl.) regained suppression (27 ng./dl.) 14 days after the second injection (day 98). At study completion all patients had 50 ng./dl. or less testosterone (mean plus or minus standard error of mean 10.1 +/- 0.07) and 104 of the 111 (94%) had 20 ng./dl. or less. From baseline to month 6 mean luteinizing hormone decreased from 9.2 +/- 1.1 to 0.08 +/- 0.01 mIU/ml. and mean prostate specific antigen decreased more than 98%. No flare reactions were observed and patient assessments of bone pain and urinary symptoms were unchanged. The most common treatment related adverse event was hot flashes, which were mild in 57% of cases, moderate in 12% and severe in 0%.. LA-2550 (22.5 mg. depot) produced and maintained safe and effective suppression of serum testosterone to well below the medical castrate level of 50 ng./dl. or less.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Humans; Injections, Subcutaneous; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

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

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

The safety, efficacy, and pharmacokinetics of monthly subcutaneous injections of a new leuprolide acetate (LA) depot formulation were investigated in patients with advanced prostate cancer.. The 2-part, 6-month (168-day), open-label, multicenter study enrolled male patients diagnosed with adenocarcinoma of the prostate (Jewett stage C or D). LA-2500 7.5-mg (a new subcutaneous depot formulation containing 7.5 mg of LA) injections were administered at monthly (28-day) intervals. The primary efficacy parameter was total serum testosterone level. A breakthrough response was defined as a single testosterone measurement > 50 ng/dL after achieving castration testosterone levels. Testosterone was isolated from sera by alumina column chromatography and measured by radioimmunoassay (RIA). LA was purified by solid-phase extraction and high-performance liquid chromatography and was then quantitated by RIA.. One hundred seventeen of the 120 enrolled patients completed the 6-month study. Three patients withdrew for reasons not related to treatment. LA had a mean (SD) maximal concentration of 26.3 (12.6) ng/mL at 4.66 (1.44) hours and was detected for a mean of 37 days (range, 28-49 days). By day 28, 94.1% (112/119) of the patients achieved medical castration (serum testosterone < or = 50 ng/dL). By day 42, 100.0% (118/118) of the patients remaining in the study had serum testosterone levels < or = 50 ng/dL and 97.5% (115/118) had levels < or = 20 ng/dL. At study completion, the mean (SD) serum testosterone level was 6.12 (4.3) ng/dL (range, 3.0-27.0 ng/dL). No breakthrough or acute-on-chronic responses were reported throughout the study. From baseline to month 6, mean (SD) luteinizing hormone level decreased from 8.0 (7.3) mIU/mL to 0.09(0.1) mIU/mL, and mean (SD) prostate-specific antigen level decreased from 32.9 (86.3) ng/mL to 3.2 (12.0) ng/mL. Treatment-related adverse events were reported by 74.2% (89/120) of patients, the most common being hot flashes (56.7%).. This 6-month, open-label, noncontrolled study showed LA-2500 7.5-mg depot was well tolerated and maintained testosterone suppression (< or = 50 ng/dL) in the patients completing the study without any testosterone breakthrough responses.

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

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

Flare-up phenomena, such as an increase in prostate-specific antigen (PSA) and/or deterioration of symptoms, are observed in some patients undergoing gonadotropin-releasing hormone (GnRH) agonist therapy. This study was carried out to determine the optimal time for starting the administration of flutamide to prevent flare-up phenomena.. Twenty-six patients with prostate cancer and elevated serum levels of PSA were randomly assigned to 5 groups. Group A patients (n = 6) were treated with a subcutaneous injection of 3.75 mg leuprorelin acetate depot alone. Group B, C, D and E patients (5 patients in each group) were treated with 375 mg/day of orally administered flutamide combined with leuprorelin. Flutamide was initiated on the day of leuprorelin injection in group B, and at 1, 2 and 4 weeks before leuprorelin injection in groups C, D and E, respectively. Serum PSA and testosterone levels were measured in each patient.. Pretreatment with flutamide increased the serum testosterone level, but the testosterone surge after leuprorelin administration was almost the same in all 5 treatment groups. In patients who had been treated with flutamide in combination with leuprorelin, the mean PSA level did not exceed the pretreatment levels after leuprorelin administration. The rate of decrease in PSA in the group receiving simultaneous administration of flutamide with leuprorelin showed a decline comparable to that during the period before leuprorelin administration in the flutamide pretreatment groups.. Simultaneous administration of flutamide with a GnRH agonist is sufficient to prevent flare-up phenomena.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Time Factors

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

This prospective, randomized, multicenter comparative trial studied the effect of neoadjuvant hormonal treatment (NHT) prior to radical, prostatectomy.. Histopathologic tissue specimens were obtained from 91 consecutive patients (aged 60-70 years) who underwent a radical prostatectomy for stage B prostate adenocarcinoma. The patients had received NHT for three months. Specimens were compared with those from 48 age-matched control patients who underwent similar surgery for stage B disease without receiving preoperative therapy.. Treated tumors with an acinar pattern were distinguishable from the untreated tumors by neoplastic acini that appeared shrunken and areas of individual infiltrating tumor cells separated by an abundant interglandular connective tissue. The epithelial tumor cells had inconspicuous nucleoli, nuclear shrinkage, chromatin condensation and pyknosis, cytoplasmic clearing, and enlargement by coalescence of vacuoles and rupture of cell membranes. No mitotic figures were seen in any treated tumors.. Preliminary results show a benefit for patients receiving NHT in regard to the histologic indicators that we evaluated.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Cyproterone Acetate; Diagnosis, Differential; Humans; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Prospective Studies; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms

Intermittent androgen suppression (IAS) has been suggested as a means of attenuating the androgen deprivation syndrome in men with incurable prostate cancer. Laboratory data suggest that intermittent therapy may prolong the duration of androgen dependence.. Since October 1993, 54 patients have entered a Phase II protocol consisting of 8 months of total androgen blockade (TAB) using leuprolide (Lupron) depot and nilutamide (Anandron) followed by an off-treatment interval of variable length. Eleven patients had biopsy-proven local failure after radiotherapy, 4 had biochemical failure, 24 had distant metastases (fewer than six axial sites on bone scan), 11 had combined local and distant failure, and 4 were treated as primary management for nodal disease. Mean prostate-specific antigen (PSA) at entry was 37 ng/mL (range 3.8 to 196). After 8 months of TAB, hormonal therapy was discontinued for those patients whose PSA was less than 4.0 ng/mL and stable or decreasing and was resumed (cycle 2) when PSA increased to greater than 10 ng/mL.. As of April 1 998, mean follow-up was 33 months (range 14 to 53). Patients have completed at least one, and up to five treatment cycles. The mean time to nadir PSA in cycle 1 was 20 weeks, and the mean time off was 35 weeks (31 weeks for those with metastatic disease versus 39 for local or biochemical failure). In cycle 2, the mean time to PSA nadir was 17 weeks, and the mean time off was 30 weeks (28 weeks for metastatic disease and 38 weeks for local or biochemical failure). In cycle 3, the time to PSA nadir was 19 weeks. Full testosterone data are available for 40 patients in cycle 1. Normal levels were achieved during the off-treatment interval in 73% by a mean of 18 weeks (median 9). Testosterone normalization in cycle 2 was achieved in 71% at a mean time of 17 weeks (median 14).. TAB can be used intermittently, and appears to be more appropriate for patients with local or biochemical failure. Testosterone recovery is not universal in the off-treatment intervals. IAS needs to be investigated in a randomized trial to determine the effect on overall survival and quality of life.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Follow-Up Studies; Humans; Imidazoles; Imidazolidines; Leuprolide; Male; Prostatic Neoplasms

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

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

To evaluate the efficacy of chemoendocrine therapy for the initial treatment of stage D2 prostate cancer, we conducted a prospective randomized study which compared combined androgen blockade alone to that combined with UFT. Twenty-one patients received LH-RH agonist and flutamide (Group-A), and 23 patients received LH-RH agonist, flutamide and UFT (Group-B). The overall response rate and the PSA response rate of Group-A was 71.4% and 100% respectively, against 65.2% and 90%, respectively in Group-B. The median follow-up period was 24 months. The 2-year progression-free survival rate of Group-A was 7.4% and that of Group-B was 15.9%. The response rate and progression-free survival rate did not differ significantly between the 2 groups. Liver dysfunction due to flutamide was common in both groups, and a total of 4 patients did not continue the treatment because of this adverse effect. We conclude that in patients with stage D2 prostate cancer, treatment with combined androgen blockade and UFT is not superior to treatment with combined androgen blockade alone.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antimetabolites, Antineoplastic; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Flutamide; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Prostatic Neoplasms; Tegafur; Treatment Outcome; Uracil

An unblinded, multicenter study to evaluate the efficacy and safety of a long-acting depot formulation of leuprolide (30 mg injected intramuscularly every 16 weeks) was carried out in 49 patients with Stage D2 prostate cancer.. Clinical evaluations were performed every 16 weeks, and serum testosterone levels were monitored biweekly or weekly for 32 weeks.. The mean serum testosterone level for the 45 evaluable patients fell to the castrate range (50 ng/dL or less) by week 3 after the initial depot injection and remained at that level throughout the initial 32-week treatment period. The median time to the onset of castrate levels was 22 days (range 9 to 43). Onset of castrate levels of testosterone was achieved within 4 weeks of the initial depot injection in 96% of patients. One patient (2%) experienced a transient "escape" (testosterone levels greater than 50 ng/dL on two consecutive determinations). Delay of an injection by up to 3 weeks did not have an effect on testosterone suppression. Objective tumor response (no progression) occurred in 90% of patients at week 16 and in 80% at week 32. Prostate-specific antigen and prostatic acid phosphatase decreased by 50% or more at week 32 in 97% and 76% of patients, respectively. Assessment of local disease status and overall performance status showed improvement or stability in most patients. The most common adverse events were hot flashes (45%), back pain (16%), and arthralgia (14%).. The 30-mg depot formulation of leuprolide, which acts in a manner similar to the 7.5- and 22.5-mg depot formulations (given monthly and every 3 months, respectively) is effective in lowering serum testosterone to castrate levels in all patients and demonstrates a favorable response in 80% of the patients with advanced prostate cancer for the 32-week observation period. The drug was well tolerated in all patients.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Delayed-Action Preparations; Disease Progression; Drug Administration Schedule; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

In the last few years, the role of neoadjuvant hormonal treatment (NHT) prior to radical prostatectomy has been largely debated and investigated in randomized multicenter trials as well as in large single-institution studies. We have initiated a prospective randomized comparative trial with parallel groups in patients with clinically limited disease to contribute to the clarification of the possible role of NHT; to evaluate the efficacy of NHT with leuprolide plus cyproterone acetate in 'maintaining' the stage of the disease; to reduce the percentage of pathological overstaging, and mainly to accurately assess the pathological modifications induced by NHT. The present paper is an interim report of the results.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoma in Situ; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cyproterone Acetate; Delayed-Action Preparations; Diagnosis, Differential; Disease-Free Survival; Drug Administration Schedule; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Prostatectomy; Prostatic Diseases; Prostatic Hyperplasia; Prostatic Neoplasms

To establish the pharmacodynamic and safety equivalence between 2 sustained-release forms of leuprorelin 11.25 mg and 3.75 mg, in the treatment of metastatic prostatic carcinoma.. 44 patients received subcutaneous injections of leuprorelin for 9 months (randomization: 2/l): either 11.25 mg every three months (n = 29) or 3.75 mg monthly (n = 15). Main criterion: centralized monthly assay of plasma testosterone (T).. The equivalence of the 2 forms in terms of mean plasma testosterone was demonstrated (p = 0.002): 1 month: T = 0.19 +/- 0.03 ng/ml; 3 months: T = 0.27 +/- 0.04 ng/ml. Exploratory analysis did not reveal any significant difference between the groups for the number of patients castrated at each visit or for the number of patients with all T values < or = 0.5 ng/ml, or for clinical responses or safety.. The 2 forms have a comparable efficacy and safety.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Chemistry, Pharmaceutical; Delayed-Action Preparations; Humans; Leuprolide; Male; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Therapeutic Equivalency; Treatment Outcome

Comparative efficacy and safety of 2 LHRH analogues in metastatic prostatic carcinoma.. 68 patients received monthly injections for 6 months (randomization): either subcutaneous leuprolide 3.75 mg LP (n = 36), or intramuscular triptorelin 3.75 mg LP (n = 32). (Flare-up prevention: nilutamide). Parameters re-evaluated at 1.3 and 6 months: centralized assays of plasma testosterone (T), LH and serum PSA; clinical symptoms. Main criterion: proportion of patients with T < or = 0.5 ng/mL.. The percentages of patients with T < or = 0.50 ng/mL was not significantly different between the two groups and were equal to 100 and 90%, 97 and 100%, and 100 and 96% at the 3 study times, for leuprolide or triptorelin, respectively. The difference was significant at 1 month on complementary analysis at the limit of T < 0.30 ng/mL: 86% with leuprolide versus 60% with triptorelin (p = 0.02) and for mean plasma testosterone: 0.16 +/- 0.10 ng/mL versus 0.33 +/- 0.44 ng/mL, respectively (p = 0.02). The clinical subjective efficacy was not significantly different.. Both treatments were effective, although plasma testosterone fell more rapidly with leuprolide. No conclusion about the possible clinical or survival benefits can be formulated. Overall safety was satisfactory.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Data Interpretation, Statistical; Drug Tolerance; Humans; Imidazoles; Imidazolidines; Injections, Intramuscular; Injections, Subcutaneous; Leuprolide; Male; Middle Aged; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Time Factors; Triptorelin Pamoate

Thanks to earlier detection of clinically significant prostatic adenocarcinoma by measurement of serum prostate-specific antigen (PSA) levels, increasing numbers of patients are undergoing radical prostatectomy. However, the curative potential of this procedure is seriously limited by clinical understaging, which results in positive surgical margins and a marked increase in disease progression. In a multicenter study, histopathologic evaluation of radical prostatectomy specimens showed that presurgical androgen deprivation with leuprolide plus flutamide reduced the incidence of surgical margin involvement by 62%. In patients who received androgen deprivation therapy, characteristic and recognizable histopathologic changes in nontumor glands included atrophy, basal cell prominence, vacuolated luminal cell layers, and squamous and transitional cell metaplasia. Androgen deprivation markedly reduced the incidence of prostatic intraepithelial neoplasia (PIN) to 35%. The effects of androgen deprivation on prostatic carcinoma included smaller tumor glands, pyknosis and empty glandular spaces, and vacuolization and degeneration of tumor cells with an inflammatory response. Similar but less pronounced changes with no decrease in PIN were observed in finasteride-treated patients. It is important for pathologists to be aware of these histological changes and process tissue appropriately, because the changes affect the recognition and histological grading of tumors in radical prostatectomy specimens.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Flutamide; Humans; Leuprolide; Male; Neoplasm Staging; Premedication; Prostatectomy; Prostatic Neoplasms

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

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

To compare the 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

A prospective evaluation of neoadjuvant hormonal downsizing in patients with localized carcinoma of the prostate was undertaken to assess its effect on normal tissue irradiation. Twenty patients with stage T1 or T2 (A, B) carcinoma of the prostate received 3 months of Lupron prior to definitive radiotherapy. The volumes of the prostate, seminal vesicles, bladder, and rectum from both the pre- and posthormone treatment planning CT were entered onto a 3-D treatment-planning system. The treatment planning parameters were standardized to facilitate comparison of the pre- and posthormonal volumes. Following the three monthly injections of Lupron, the average volume of the prostate was reduced by 37%. As a consequence, the volume of the bladder receiving at least 40, 52, and 64 Gy was reduced by an average of 15, 18, and 20%, respectively. In addition, the volume of the rectum receiving at least 40, 52, and 64 Gy was reduced by an average of 13, 20, and 34%, respectively. In conclusion, in patients with localized prostate cancer, downsizing of the prostate resulted in a reduction in the volume of bladder and rectum receiving high radiation doses. This approach may result in an improvement in the therapeutic ratio by reducing the morbidity of treatment.

Topics: Adenocarcinoma; Chemotherapy, Adjuvant; Humans; Leuprolide; Male; Neoplasm Staging; Prospective Studies; Prostate; Prostatic Neoplasms; Rectum; Tomography, X-Ray Computed; Urinary Bladder

Evaluation of the prognostic value of prostatic markers with regard to disease progression after endocrine therapy in patients with prostate carcinoma. A total of 51 patients (21 stage C, 5 stage D1 and 25 stage D2). Endocrine therapy consisted in complete hormonal blockade with flutamide and an LH-RH analog depot (leuprolide). PSA-PAP levels were determined both pre-treatment and during follow-up of patients using radioimmunometric techniques. Follow-up extended for 13 to 62 months (mean 30 months). Death due to progression happened in 24 of 51 patients. Previous PSA levels did not correlate to progression. Changes in PSA levels during treatment and time scope when they occurred were associated to subsequent evolution. Patients with PAP higher than 10 ng/ml at the beginning of therapy experienced higher progression rates (p < 0.05). Decrease of PSA levels by a percentage greater than 80% during the first quarter of treatment relative to initial figures was related to lower progression rates (p < 0.01). Maintenance of high levels in the first six months of treatment predicted a higher progression rate (p < 0.001). The study suggests a better prognosis for patients wit decreased serum PSA rates by a percentage of around 80% after one to three months treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Flutamide; Follow-Up Studies; Humans; Leuprolide; Male; Prognosis; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms

Seventy-two patients were admitted in a multicentre trial with the purpose of assessing the clinical efficacy and safety of the hormonal control and tolerance of leuprolide acetate in a once-a-month depot injection formulation for the treatment of disseminated prostate cancer. During a 1-year follow-up, there were ten withdrawals for different reasons. At baseline and at 6 months of treatment the following parameters were evaluated: clinical examination, routine blood analysis, PAP, PSA, LH and testosterone, as well as bone scan. LH and testosterone determinations were repeated at 2, 4, 8, 12, 16, 20 and 24 weeks. Testosterone reached castration levels within the second week and was maintained until the end of the study. In agreement with the NPCP criteria, 65 patients were assessed as: complete response 3%, partial response 40%, disease stabilization 36%, and progression 21%. In summary, a once-a-month injection of leuprolide acetate offers a safe and effective alternative to surgical castration.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Delayed-Action Preparations; Drug Administration Schedule; Follow-Up Studies; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms

Prostatic intraepithelial neoplasia (PIN) is considered the most likely precursor of prostatic adenocarcinoma. The effect of androgen deprivation therapy on the prevalence of PIN is unknown.. We undertook a case-control study of radical retropubic prostatectomies from 24 treated patients and a control group of 24 untreated patients matched for age and clinical stage (all T3). Androgen deprivation therapy included LHRH agonist leuprolide and flutamide (18 patients), diethylstilbestrol (DES) (2 patients), DES with leuprolide and flutamide (1 patients), and orchiectomy (3 patients). Prostatectomy specimens were evaluated for the presence and extent of high-grade PIN according to the number of high-power microscopic fields, and nuclear tumor grade (1 to 4 scale) and Gleason score were also determined.. The prevalence of high-grade PIN in pretreatment transrectal needle biopsies was similar in the treated and untreated groups. The prevalence and extent of high-grade PIN were lower in cases treated with androgen deprivation therapy than controls. Nuclear tumor grade was also lower in treated patients, but there was a paradoxical increase in the Gleason score. The prevalence of aneuploidy in the cancers was similar in both groups.. These findings suggest that androgen deprivation therapy decreases the prevalence and extent of high-grade PIN.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Carcinoma in Situ; Case-Control Studies; Combined Modality Therapy; Diethylstilbestrol; Flutamide; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary; Orchiectomy; Prevalence; Prostatectomy; Prostatic Neoplasms

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leuprolide; Male; Middle Aged; Pancreatic Neoplasms; Tamoxifen

This report describes the effects of neoadjuvant hormonal therapy on 16 patients (mean age = 65 y) with clinical stage C adenocarcinoma of the prostate (CaP) who underwent radical prostatectomy from December 1991 to June 1993 at the University of Colorado Health Sciences Center. Staging of CaP was determined by digital rectal exam, transrectal ultrasonography (TRUS), radionuclide bone scanning, abdominal and pelvic computed tomography scanning, transrectal coil magnetic resonance imaging, and serum acid phosphatase. Most patients underwent a laparoscopic lymph node dissection to rule out micrometastasis. Every patient was treated for 4 months with a combination of a gonadotrophin-releasing hormone (GnRH) agonist (Lupron) and an anti-androgen (flutamide, Eulexin). Serial prostate-specific antigen (PSA) levels, post-treatment prostate volume measured by TRUS, and whole-mount sectioning of the surgical specimen were studied. The PSA levels decreased from a mean of 39.1 ng/ml (Hybritech method) to a mean of 0.43 ng/ml; (p < 0.0001). Prostate volumes in all patients demonstrated a mean decrease of 52% (p < 0.0001), and pathological effects of hormonal deprivation were observed in all patients. By whole-mount sectioning of the radical prostatectomy specimens, 3 patients had organ-confined disease (stage B), 6 showed invasion of the capsule with surgical margins free of tumor (stage C1), 3 had extracapsular extension with positive surgical margins (stage C2), and 4 had extracapsular extension with seminal vesicle involvement (stage C3). We conclude that by downsizing and markedly decreasing serum PSA values, neoadjuvant hormonal therapy offers an alternative treatment for stage C carcinoma of the prostate.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Flutamide; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Pilot Projects; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Although the only opportunity to cure prostate cancer is treatment at an early stage, radical prostatectomy has remained relatively unpopular because 40-50% of prostate cancers estimated at diagnosis as confined to the prostate are found to be at a more advanced stage following histopathological analysis of the surgical specimen. This first prospective, randomized trial investigated the potential advantages of 3-month neoadjuvant combination therapy with flutamide and lupron before radical prostatectomy vs. prostatectomy alone in early stage prostate cancer. Cancer-positive margins were reduced from 38.5% (25 of 65) in control patients to only 13.0% (10 of 77) in men who received neoadjuvant combination therapy with the antiandrogen flutamide and the luteinizing hormone-releasing hormone (LHRH) super-agonist Lupron before radical prostatectomy (p = 0.006). Moreover, comparison of the final stage determined by histopathological examination of the surgical specimen with that estimated at diagnosis showed that a more advanced stage (upstaging) was found in 53.8% of controls, but patients who received combination therapy had an opposite effect: a more favorable stage than expected at diagnosis was found in 23.4% of cases (downstaging), a 77.2% advantage of neoadjuvant combination therapy. The concern about radical prostatectomy, underestimation of stage, is thus markedly improved by 3-month neoadjuvant therapy with flutamide and a LHRH superagonist. Cancer-negative margins are expected to be accompanied by a life expectancy not different from that of men of similar age with no prostate cancer; therefore, the present data, combined with efficient detection of early stage prostate cancer, offer the basis for dramatic improvement in the morbidity and mortality of prostate cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Flutamide; Follow-Up Studies; Humans; Leuprolide; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms

In a recent intergroup study under the auspices of the National Cancer Institute, 603 eligible patients with newly diagnosed disseminated adenocarcinoma of the prostate were prospectively randomized in a double-blinded clinical trial to receive either a gonadotropin-releasing hormone analogue (leuprolide) and a nonsteroidal antiandrogen (flutamide) or leuprolide and placebo. Of the 603 eligible patients, 300 were in the leuprolide and placebo arm and 303 were in the leuprolide and flutamide arm. At the time of disease progression, the code was broken: Those patients in the placebo arm were given the opportunity to receive flutamide, and the patients in the flutamide arm were treated at their physician's discretion. There was no survival time distribution difference, based on survival measured from the progression data, between the patients who were received flutamide after progression and those who were treated at their physician's discretion after progression. Furthermore, the addition of flutamide to leuprolide at the time of disease progression resulted in a survival-time distribution that is similar to other treatments of hormone-refractory prostate cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Flutamide; Humans; Leuprolide; Male; Neoplasm Metastasis; Prospective Studies; Prostatic Neoplasms; Regression Analysis; Survival Rate

To determine the efficacy of recombinant human leukocyte alpha-interferon (IFL-RA) in advanced hormone-refractory prostate cancer, the authors treated 40 patients with IFL-RA administered intramuscularly at a dose of 10 x 10(6) U/m2 three times weekly. Toxicity was substantial and necessitated at least a 50% dose reduction in all but five patients during the first 1-2 months of therapy. No responses were observed in patients with bone metastases, but complete and partial regression of nodal disease were observed in two patients with extraosseous disease (overall response rate, 5%; 95% confidence interval, 0.64-17.75%). The authors conclude that IFL-RA cannot be recommended at this dose and schedule in patients with advanced prostate cancer, but additional study of its use in patients with nodal disease may be warranted.

Topics: Adenocarcinoma; Aged; Clinical Protocols; Humans; Interferon-alpha; Leuprolide; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Recombinant Proteins; Remission Induction

Twenty-five evaluable patients with advanced or recurrent epithelial ovarian carcinoma that was no longer controllable with surgery, radiation therapy, and/or chemotherapy were treated with leuprolide acetate, a gonadotropin-releasing hormone agonist, 1 mg subcutaneously daily. One partial response (4%) was observed among the 25 patients. The upper 95% confidence bound of the response rate is 17.6%. Fifteen patients (60%) exhibited stable disease for at least 8 weeks, and 9 patients (36%) developed progressive cancer while receiving treatment. The regimen was well tolerated with no patient experiencing life-threatening toxicity. Mild toxicities included leukopenia in 2 patients (8%), thrombocytopenia in 2 patients (8%), gastrointestinal toxicity in 5 patients (20%), anemia in 4 patients (16%), hot flashes in 1 patient (4%), and facial swelling in 1 patient (4%). Thus, leuprolide acetate was well tolerated but has insignificant activity in treating patients with chemotherapy-refractory ovarian adenocarcinoma.

Topics: Adenocarcinoma; Aged; Drug Evaluation; Female; Humans; Leuprolide; Ovarian Neoplasms

Fifteen patients with previously untreated metastatic prostate cancer were treated on a pilot trial with a combination of maximal androgen blockade plus intermittent cytotoxic therapy after androgen priming to stimulate cell division. Androgen blockage was carried out using a gonadotropin-releasing hormone analog (leuprolide) plus a nonsteroidal antiandrogen (flutamide). Carboplatin (CBDCA) (800 mg/m2) was given intravenously every 28 days, preceded for 3 days and followed for 3 days by androgen treatment with fluoxymesterone (5 mg orally twice a day), during which time flutamide was discontinued. Three patients (20%) achieved a complete response (CR), and eight patients (53.3%) achieved a partial response (PR). Four patients (26.7%) had stable disease (SD). The median progression-free survival (PFS) time was 31 months. Nine of 15 patients (60%) remain alive with a median follow-up time of 42+ months (range, 22 to 54 months). Grade 4 thrombocytopenia and Grades 3 or 4 leukopenia were experienced in 87% and 80% of patients, respectively, requiring dose reductions of CBDCA in 85% of the cycles. Six of 15 patients experienced a flare in bone pain with androgen priming. There were no associated spinal cord compressions; however, exclusion of impending spinal cord compression was required before entrance on study.

Topics: Adenocarcinoma; Aged; Androgens; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Drug Evaluation; Fluoxymesterone; Flutamide; Humans; Leuprolide; Male; Middle Aged; Neoplasms, Hormone-Dependent; Pilot Projects; Prostatic Neoplasms; Remission Induction; Survival Analysis

A study carried out in 470 patients with metastasized adenocarcinoma of the prostate confirmed the efficacy of 3.75 mg leuprorelin acetate depot given subcutaneously once monthly. Bone pain was rapidly decreased and the general condition of patients and urinary signs improved. Sexual activity was maintained in 50% of patients. After 3 months' treatment, there was no progression in 95% of patients, complete regression in 39% and partial regression in 49%; 17% of cases were stabilized. Improvement in clinical signs was directly related to a decline in amounts of prostate-specific antigen and was associated with a decline in serum testosterone concentrations within 3-4 weeks of starting treatment. Leuprorelin acetate depot was well tolerated and was easy to store and use.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Antineoplastic Agents; Bone Neoplasms; Clinical Trials as Topic; Delayed-Action Preparations; France; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Lymphatic Metastasis; Male; Middle Aged; Multicenter Studies as Topic; Prostate-Specific Antigen; Prostatic Neoplasms; Sexual Behavior

Combined therapy, the treatment of advanced adenocarcinoma of the prostate by total androgen suppression, is still a controversial subject today. Some studies performed during the 1980s support the value of this therapeutic approach, while others have found it to be no more effective than surgical or chemical castration alone. Recently, the results of a randomized, controlled, multicenter intergroup study of combined therapy sponsored by the U.S. National Cancer Institute (NCI) became available. These results suggest that combined therapy offers some advantages over monotherapy in the treatment of advanced prostate cancer. A variety of drugs are available to suppress adrenal androgens. However, the value of these agents in prostate cancer therapy continues to be hotly debated.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents; Combined Modality Therapy; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Orchiectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic

Leuprolide is a new, potent analogue of gonadotropin-releasing hormone which, after an initial transient stimulation, causes a profound suppression of serum gonadotropins and testosterone. One hundred eighteen patients with advanced carcinoma of the prostate have undergone treatment with leuprolide in a multi-institutional trial. Minimal evidence of objective response was seen in patients who had failed prior endocrine therapy with orchiectomy or estrogens. In patients without previous hormonal treatment, leuprolide induced an objective disease response (72%) comparable to alternative primary endocrine therapy. Considering the lack of significant side effects seen with long-term GnRH agonists, compounds such as leuprolide may prove to be the preferred initial endocrine therapy for selected patients with metastatic carcinoma of the prostate.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Castration; Clinical Trials as Topic; Diethylstilbestrol; Dihydrotestosterone; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Testosterone

In a controlled, prospective, randomized clinical trial, we evaluated the safety and efficacy of leuprolide, a superactive analog of luteinizing hormone releasing hormone, given in a single subcutaneous injection dose of 1 mg per day, versus diethylstilbestrol (DES) 3 mg per day by mouth in patients with previously untreated Stage D2 prostatic adenocarcinoma. Eleven leuprolide patients and 10 DES patients were evaluated for therapeutic response. Eighty per cent of patients in each group experienced subjective improvement in bone pain and urinary obstructive signs and symptoms. Although the pooled percentages of complete, partial, and stable objective responses were greater for the leuprolide group than the DES group, the sums of the percentages of complete and partial objective responses were comparable for both treatment groups during the first forty-eight and sixty weeks of the study, respectively. In addition, patients not responding to leuprolide generally experienced no benefit with crossover to DES, and vice versa. Serious adverse reactions were more common in the DES group and included fatal myocardial infarction, arrhythmia, deep venous thrombosis, and gynecomastia. Vasomotor flushing, disease flare, and injection site irritation occurred most often in leuprolide patients, but did not require modification or discontinuation of treatment.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Agents; Clinical Trials as Topic; Diethylstilbestrol; Dihydrotestosterone; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Prostate; Prostatic Neoplasms; Random Allocation; Testosterone; Time Factors

Potent synthetic analogs of gonadotropin-releasing hormone produce parodoxical antireproductive effects when administered chronically. These compounds are minimally toxic and may exhibit no plateau of the dose-response curve even at very high doses. These considerations served as the basis for our systematic evaluation of [D-leucine6-desarginine-glycine-NH2(10)]gonadotropin-releasing hormone (GnRH-A) proethylamide in the very high dose range (i.e., 10-fold larger amounts than previously used). In rats given the analog for 12 wk, prostate, testis, and seminal vesicle weights were suppressed to a greater extent with 200 micrograms q.d. than with 40 micrograms q.d. (P less than 0.01 prostate, less than 0.01 testis, less than 0.01 seminal vesicles), indicating dose-response effects in the very high dose range. 200 micrograms of [D-Leu6-des-Gly-NH2(10]-GnRH-A consistently suppressed leutinizing hormone (LH) values at 6 and 12 wk (basal 71 +/- 9.5; 6 wk 34 +/- 3.8; 12 wk 28 +/- 5 ng/ml) whereas 40 micrograms suppressed LH variably (basal 33 +/- 3.8; 6 wk 17 +/- 3.9; 12 wk 32 +/- 5.2). Testosterone fell to 15 +/- 2.4 and 19 +/- 2.0 ng/100 ml in response to 200 micrograms q.d. and to 27 +/- 6.4 and 22 +/- 7.4 ng/100 ml with the 40-micrograms dose. These findings in the rodent prompted treatment of stage D prostate cancer patients with similarly high doses of [D-Leu6-des-Gly-NH2(10)]-GnRH-A. After treatment for 11 wk with 1,000 or 10,000 micrograms/d of the analog, testosterone and dihydrotestosterone levels transiently rose and then fell into the surgically castrate range (testosterone 19 +/- 4.4 ng/100 ml [D-Leu6-des-Gly-NH2(10)]-GnRH-A vs. surgically castrate 11 +/- 0.9 ng/100 ml, P = NS; dihydrotestosterone 15 +/- 1.7 ng/100 ml GnRH-A vs. surgically castrate 15 +/- 4.1 ng/100 ml. P = NS). However, unlike the chronic stimulatory effect on the pituitary at lower doses, very high dose therapy resulted in profound suppression of plasma and urine LH. Plasma levels fell to the limit of assay detectability, whereas the more sensitive urinary assay detected prepubertal levels of excretion (i.e., 64 +/- 8.4 mlU/h). The highly sensitive rat interstitial cell testosterone bioassay for LH also demonstrated a marked decline in LH to undetectable levels in 17/19 subjects. Clinical results with [D-Leu6-des-Gly-NH2(10)]-GnRH-A simulate those achieved by surgical castration in men with prostatic cancer as suggested by available preliminary data.

Topics: Adenocarcinoma; Adult; Animals; Castration; Clinical Trials as Topic; Dihydrotestosterone; Dose-Response Relationship, Drug; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Leuprolide; Luteinizing Hormone; Male; Prostatic Neoplasms; Rats; Testis; Testosterone

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

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

The roles of estrogen receptors (ERs) and the efficacy of anti-estrogen (E2) therapies in pancreatic cancer stay controversial. The main objectives of this study were to investigate the potential roles of ERs in tumor progression and endocrine therapies.. The ER expression status in PANC-1 and SW1990 pancreatic cancer cell lines was determined. SRB assay, colony formation assay and proliferation assay were used to investigate the responses of these cells to E2. ERα-selective agonist propylpyrazoletriol (PPT), ERβ-selective agonist diarylpropionitrile (DPN), ERα over-expressed SW1990 cells, ERα knock-out PANC-1 cells and patient-derived xenografts (PDX) were applied to investigate the potential roles of ERα in pancreatic cancer. The phosphorylation of ERα-related signaling molecules extracellular regulated protein kinases (ERK1/2) and protein kinase B (AKT) were investigated. The in vivo anti-tumor efficacy and safety of letrozole (LTZ) combined with leuprorelin acetate (LA) and gemcitabine (GEM) were also preliminarily studied.. PANC-1 cells expressed much more ERα than SW1990 cells, and ERβ level was with less diversity. Accordingly, the proliferation of PANC-1 rather than SW1990 cells could be stimulated by E2, and only PANC-1 could respond to LTZ endocrine therapy in female but not male mice. The phosphorylation of ERK1/2 but not AKT was altered by over-expressed or knocking out of ERα with or without the addition of E2 and LTZ. The combination therapy of LTZ and GEM showed acceptable efficacy and safety.. This study showed the important roles of ERα in tumor progression and endocrine therapies of pancreatic cancer in women.

Topics: Adenocarcinoma; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Deoxycytidine; Estradiol; Estrogen Receptor alpha; Estrogen Receptor Modulators; Female; Gemcitabine; Gene Expression; Gene Knockout Techniques; Humans; Letrozole; Leuprolide; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Pancreatic Neoplasms; Xenograft Model Antitumor Assays

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Agents, Hormonal; Arm; Delayed-Action Preparations; Granuloma, Foreign-Body; Humans; Injection Site Reaction; Injections, Subcutaneous; Leuprolide; Male; Microspheres; Neoplasm Grading; Prostatic Neoplasms; Skin

An 83 year-old male with Gleason score 4+3 prostatic adenocarcinoma status post brachytherapy developed obstructive voiding symptoms 9 years after brachytherapy. Prostate-specific antigen was 0.67. Cystoscopy noted multiple papillary urethral tumors concerning for primary urethral carcinoma. Immunophenotype of biopsies supported diagnosis of Gleason score 4+4 prostatic adenocarcinoma. Androgen deprivation therapy was started. Cystoscopy performed 4 years later, for microhematuria workup, noted complete resolution of the urethral tumors. We present a patient with little serum Prostate-specific antigen change with urethral prostatic adenocarcinoma metastasis that resolved after androgen deprivation therapy.

Topics: Adenocarcinoma; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Humans; Leuprolide; Male; Nitriles; Prostatic Neoplasms; Remission Induction; Tosyl Compounds; Urethral Neoplasms

Topics: Adenocarcinoma; Administration, Topical; Aged; Antineoplastic Agents, Hormonal; Carcinoma; Collagen Diseases; Glycation End Products, Advanced; Humans; Japan; Leuprolide; Male; Neoplasm Metastasis; Prostatic Neoplasms; Skin Diseases, Genetic; Steroids; Treatment Outcome; Ultraviolet Therapy

Gonadotropin-releasing hormone (GnRH) agonists are widely used in hormone therapy for prostate cancer. We report a patient with pituitary apoplexy following this therapy as a rare complication and review the related literature. A 62-year-old man presented with elevated prostate specific antigen. Transrectal ultrasound guided biopsy of the prostate gland revealed adenocarcinoma. Whole-body (18)F-fluorodeoxyglucose (FDG) positron emission tomography/CT scan showed FDG-uptake in the pituitary region. MRI also demonstrated a pituitary tumor, diagnosed as an incidental non-functioning adenoma. The patient received his first dose of GnRH agonist (leuprolide 11.25mg) against prostate cancer. He complained of a severe headache 10 minutes after leuprolide administration and suffered from right third nerve palsy in the next 48 hours. MRI demonstrated a high intensity area on T1-weighted images, diagnosed as pituitary apoplexy. The patient underwent transsphenoidal surgery. Pathology revealed predominantly necrotic tissue and a gonadotropin secreting pituitary adenoma. Overall, 15 patients, including ours, have been reported with pituitary apoplexy after GnRH agonists with pathologic gonadotropin secreting adenoma. Fourteen of 15 patients were male. Pituitary apoplexy developed within 4 hours after administration of the agents in 8/15 patients. The combined data suggest that GnRH agonists have the potential to precipitate pituitary apoplexy in men with gonadotropin secreting adenoma. Therefore, prior to GnRH agonist therapy for prostate cancer, a known pituitary adenoma should be treated. Otherwise, the patients should be cautiously observed for any symptomatic change following drug administration.

Topics: Adenocarcinoma; Adenoma; Antineoplastic Agents, Hormonal; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Apoplexy; Pituitary Neoplasms; Prostatic Neoplasms

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Agents, Hormonal; Biopsy; Humans; Leuprolide; Male; Phlebography; Positron-Emission Tomography; Prostatic Neoplasms; Superior Vena Cava Syndrome; Tomography, X-Ray Computed; Treatment Outcome; Vascular Neoplasms

The authors describe a male patient who developed a large intracranial meningioma during the hormone therapy for pre-existing prostate cancer. A 70-year-old man received a brain check-up, and no intracranial abnormality was detected. Five months later, prostate cancer was diagnosed, and he underwent prostatectomy. Leuprorelin acetate, a luteinizing hormone-releasing hormone (LH-RH) agonist, was subsequently administered to the patient once a month for 3 years. After that he presented with a large parasagittal mass, which was excised. The tumor was histologically diagnosed as meningothelial meningioma, and LH-RH receptors were verified immunohistochemically in the cytoplasm of the tumor cells. Leuprorelin acetate may accelerate the rapid growth of meningioma in this patient.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Gastrectomy; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Meningeal Neoplasms; Meningioma; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Neoplasms, Second Primary; Nitriles; Prostatectomy; Prostatic Neoplasms; Receptors, LH; Stomach Neoplasms; Tosyl Compounds

Topics: Adenocarcinoma; Anilides; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Bone Neoplasms; Diagnosis, Differential; Fatigue; Glucocorticoids; Humans; Leuprolide; Male; Middle Aged; Nitriles; Plasma Exchange; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Purpura; Purpura, Thrombotic Thrombocytopenic; Thoracic Vertebrae; Tomography, X-Ray Computed; Tosyl Compounds; Treatment Outcome

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Brachytherapy; Diphosphonates; Humans; Imidazoles; Leuprolide; Male; Prostatic Neoplasms; Quality of Life

Cockatiels (Nymphicus hollandicus) are commonly diagnosed with ovarian neoplasia. However, there is very little information regarding medical management of this disease condition and subsequent patient response. Long-term medical therapy of 2 cockatiels eventually diagnosed with ovarian neoplasia is described along with responses to the treatment regimens. Each bird had initial signs consistent with reproductive disease (chronic egg laying, ascites, and lethargy) and respiratory distress. The diagnosis of ovarian adenocarcinoma was confirmed on postmortem examination of both birds. The birds were conservatively managed by periodic coelomocentesis and gonadotropin-releasing hormone (GnRH) agonist administration for 9 and 25 months, respectively. A positive response to GnRH agonist therapy was documented in 1 of the 2 birds. These 2 cases demonstrate that periodic coelomocentesis with or without GnRH agonist therapy may be a viable option for the long-term management of ovarian neoplasia and reproductive-organ-associated ascites in cockatiels.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Hormonal; Bird Diseases; Cockatoos; Female; Leuprolide; Ovarian Neoplasms

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Flutamide; Humans; Leuprolide; Male; Prostatic Neoplasms

Androgen deprivation therapy (ADT) for prostate cancer causes an increase in fasting insulin and adverse changes in body composition and serum lipid profile. It is unknown what other metabolic alterations are caused by ADT. To better characterize the metabolic effects of ADT, we measured changes in plasma metabolomic profile at baseline and after the first 3 months of therapy.. Fasting plasma samples were drawn from 36 subjects at baseline and after 3 months of gonadotropin releasing hormone (GnRH) agonist therapy. Extracted samples were split into equal parts for analysis on the gas chromatography-mass spectrometry and liquid chromatography/tandem mass spectrometry platforms.. Of the 292 identified metabolites, 56 changed significantly (P < 0.05) from baseline to 3 months. Notable changes were grouped as follows: (i) Multiple steroids were lower at 3 months, consistent with the effect of therapy on gonadal androgen synthesis. (ii) Most bile acids and their metabolites were higher during treatment. Cholesterol levels changed very little. (iii) Markers of lipid beta-oxidation (acetyl-carnitines and ketone bodies) and omega-oxidation were lower at 3 months. (iv) Two previously identified biomarkers of insulin resistance (2-hydroxybutyrate and branch chain keto-acid dehydrogenase complex products) were stable to lower at 3 months.. Unbiased metabolomic analyses revealed expected, novel, and unexpected results. Steroid levels fell, consistent with the effects of ADT. Most bile acids and their metabolites increased during ADT, a novel finding. Biomarkers of lipid metabolism and insulin resistance fell, unexpected given that ADT has been shown to increase fasting insulin.

Topics: 3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide); Adenocarcinoma; Antineoplastic Agents, Hormonal; Bile Acids and Salts; Gonadotropin-Releasing Hormone; Humans; Hydroxybutyrates; Insulin Resistance; Leuprolide; Lipid Metabolism; Male; Metabolome; Oxidation-Reduction; Prospective Studies; Prostatic Neoplasms; Steroids

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antithrombins; Atrial Fibrillation; Benzimidazoles; beta-Alanine; Bone Neoplasms; Brain Ischemia; Comorbidity; Dabigatran; Hematuria; Humans; Kidney Failure, Chronic; Leuprolide; Male; Prostatic Neoplasms; Pulmonary Disease, Chronic Obstructive; Secondary Prevention; Thrombophilia; Urinary Retention

Superior vena cava (SVC) syndrome is an uncommon complication of malignant disease caused by the obstruction of venous blood flow in the SVC. When present, a diagnosis of lung cancer or lymphoma will be made in approximately 95% of cases. Although other malignant diseases are occasionally associated with SVC, its occurrence in patients with prostate cancer is rare. We present a case of a patient presenting with SVC obstruction who was subsequently diagnosed with prostate adenocarcinoma. The patient has been successfully treated with GnRH agonist. This case reflects the importance of a full clinical assessment and pathological confirmation of suspected tumour prior to treatment.

Topics: Adenocarcinoma; Antineoplastic Agents; Biopsy; Diagnosis, Differential; Diphosphonates; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Lumbar Vertebrae; Lymph Nodes; Lymphatic Metastasis; Magnetic Resonance Imaging; Male; Mediastinal Neoplasms; Middle Aged; Prostatic Neoplasms; Spinal Neoplasms; Superior Vena Cava Syndrome; Thoracic Vertebrae; Tomography, X-Ray Computed

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Choroid Neoplasms; Humans; Injections, Intramuscular; Leuprolide; Male; Prostatectomy; Prostatic Neoplasms; Ultrasonography; Visual Acuity

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Brachytherapy; Diphosphonates; Humans; Imidazoles; Leuprolide; Male; Prostatic Neoplasms; Quality of Life; Zoledronic Acid

To report an unusual presentation of metastatic prostate cancer to the orbit in an immunosuppressed patient, who received a novel palliative treatment regimen.. A 56 year old HIV+ man presented with proptosis and unilateral blindness. The diagnosis, work up, and treatment are outlined.. Metastatic prostate cancer to the orbit is diagnosed, and the treatment with IMRT and hormone ablation is explored.. We outline the literature and current thinking surrounding prostate cancer metastases to the orbit. HIV+ patients currently enjoy longer life expectancies, with the caveat that their immunosuppressed status may lead to more unusual metastatic presentations. Treatments and palliation will continue to evolve as these new cases emerge.

Topics: Adenocarcinoma; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; HIV Seropositivity; Humans; Immunocompromised Host; Leuprolide; Male; Middle Aged; Nitriles; Orbital Neoplasms; Palliative Care; Prostatic Neoplasms; Radiotherapy, Intensity-Modulated; Tosyl Compounds

Disseminated carcinomatosis of the bone marrow is caused by metastasis to the bone marrow and can cause disseminated intravascular coagulation (DIC), leucoerythroblastosis, and microangiopathic hemolytic anemia (MHA). The prognosis of this syndrome is poor. We report herein two rare cases of disseminated carcinomatosis of the bone marrow in association with prostate cancer. Case 1 involved a 61-year-old man admitted to our department with elevated prostate-specific antigen (PSA) levels. Prostate biopsy revealed prostate cancer, and imaging studies were performed. Under a diagnosis of prostate cancer (T3N1Mx), the patient was treated using hormonotherapy, but died 2 months after admission due to gastrointestinal bleeding of unknown cause, refractory DIC, and cachexia. Bone marrow biopsy after his death revealed metastasis of the prostate cancer to the bone marrow. Case 2 involved a 68-year-old man admitted to our department with gross hematuria. Cystoscopy revealed non-papillary tumor in the prostatic urethra. Transurethral biopsy was performed and histology identified prostate cancer. Treatment was initiated with hormonotherapy and zoledronate. After 8 months, he complained of general fatigue and blood testing identified anemia and thrombocytopenia. Bone marrow biopsy revealed adenocarcinoma in the bone marrow. Alternative androgen therapy and chemotherapy with docetaxel was started, and the patient recovered from pancytopenia and general fatigue.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Bone Marrow Neoplasms; Carcinoma; Diphosphonates; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Fatal Outcome; Humans; Imidazoles; Leuprolide; Male; Middle Aged; Nitriles; Prostatic Neoplasms; Tosyl Compounds; Treatment Outcome; Zoledronic Acid

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Biopsy; Bone Neoplasms; Chemotherapy, Adjuvant; Humans; Leuprolide; Male; Middle Aged; Neoplasm Recurrence, Local; Osteoporosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

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

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

Prostate adenocarcinoma can manifest as a fairly indolent tumor or as a very aggressive cancer with significant invasive and metastatic potential. Common metastatic sites include bone, liver, lymph nodes, and adrenal glands. Dermatologic manifestations are rare. We present a case of a man who presented with breast skin changes that mimicked inflammatory breast carcinoma with specialized testing ultimately giving a diagnosis of metastatic prostatic adenocarcinoma. A 78-year-old man presented with left breast redness and swelling. Examination revealed an erythematous rash with subcutaneous edema over the left hemithoracic area. A breast ultrasound showed no focal mass, and a breast core biopsy had no evidence of tumor. A skin biopsy showed metastatic carcinoma in dermal lymphatics, and the tumor was found to have no estrogen or progesterone receptors or HER2 expression. Computed tomography scans, positron emission tomography, and a nuclear bone scan revealed widespread skeletal metastases. The patient received a 3-month course of capecitabine and cyclophosphamide with no improvement in his skin lesions. Subsequent immunohistochemical staining on the tumor specimen was positive for prostate-specific antigen (PSA) and alpha-methyl-CoA-racemase, confirming a diagnosis of metastatic prostatic adenocarcinoma. He received leuprolide and bicalutamide and demonstrated significant improvement with near-complete resolution of his skin lesions and a decrease in his PSA level. Prostatic adenocarcinoma presenting initially as a breast malignancy is a rarely recognizable clinical event. Undoubtedly, increased awareness and recognition of the rare entity described herein will allow for the prompt initiation of specific therapies, which might be of benefit to many patients.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms, Male; Capecitabine; Carotid Stenosis; Coronary Artery Disease; Cyclophosphamide; Deoxycytidine; Diabetes Mellitus; Fluorouracil; Humans; Immunohistochemistry; Leuprolide; Male; Nitriles; Osteoarthritis; Positron-Emission Tomography; Prostate-Specific Antigen; Prostatic Neoplasms; Pulmonary Disease, Chronic Obstructive; Tomography, X-Ray Computed; Tosyl Compounds

Platelet derived growth factor receptor inhibitor therapy improves the efficacy of taxane chemotherapy in preclinical models of prostate cancer. Men with high risk localized prostate cancer were treated with platelet derived growth factor receptor inhibitor therapy, docetaxel and hormone ablation in the preoperative setting, and clinicopathological outcomes were evaluated.. A total of 36 men with cT2 or greater disease, Gleason grade 8-10, serum prostate specific antigen more than 20 ng/ml or cT2b and prostate specific antigen more than 10 ng/ml and Gleason 7 disease, without radiological evidence of metastases, were scheduled to receive intramuscular leuprolide, 600 mg daily oral imatinib and 30 mg/m(2) weekly docetaxel x 4 every 42 days for 3 cycles before radical prostatectomy (beta [0.02, 1.98] prior on the possibility of pathological complete remission). Unresectable disease, postoperative prostate specific antigen 0.2 ng/ml or greater, or administration of postoperative radiation or hormones were defined as treatment failure.. A total of 39 men were registered over 15 months. Median patient age was 57 years (range 44 to 71). Risk factors included T3 disease (22 of 39), Gleason 8-10 disease (31 of 39) and prostate specific antigen more than 20 ng/ml (12 of 39). Three men were ineligible or declined therapy, 29 of 36 (81%) received 3 cycles of therapy and 7 of 36 (19%) discontinued therapy related to toxicity. Grades 3-4 toxicity included rash (4), diarrhea (4), fatigue (6) and neutropenia (1). The surgical approach was feasible, without excessive or unusual complications such as wound dehiscence. No pathological complete remissions were defined. At a median followup of 39 months 53% were free from progression.. Evidence for a favorable impact of platelet derived growth factor receptor inhibitor therapy on the efficacy of neoadjuvant docetaxel and hormonal ablation in high risk localized prostate cancer was not obtained.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Benzamides; Disease-Free Survival; Docetaxel; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Humans; Imatinib Mesylate; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Piperazines; Prostatic Neoplasms; Pyrimidines; Receptors, Platelet-Derived Growth Factor; Risk Factors; Survival Rate; Taxoids

Castration-resistant prostate cancer (CRPC) is an incurable disease with limited treatment options. Herbal supplements are unconventional treatments for a variety of diseases. Active hemicellulose compound (AHCC) is a Japanese supplement discovered by hybridizing several mushrooms used in traditional healing for the purpose of maintaining 'super immunity'. We report on a 66-year-old gentleman with CRPC with an excellent serologic response to AHCC. This case hypothesizes that AHCC may have potential activity against CRPC.

Topics: Adenocarcinoma; Anilides; Animals; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Basidiomycota; Combined Modality Therapy; Drug Resistance, Neoplasm; Humans; Leuprolide; Lumbar Vertebrae; Male; Nitriles; Phytotherapy; Plant Extracts; Polysaccharides; Prostate-Specific Antigen; Prostatic Neoplasms; Radioisotopes; Remission Induction; Samarium; Self Medication; Spinal Neoplasms; Tosyl Compounds

Ghrelin is a natural growth hormone segretagogue (GHS), involved in the biology of a number of diseases such as lung cancer and prostate cancer. The aim of this study is to assess the relationship existing between ghrelin and testosterone, insulin, and PSA in prostate adenocarcinoma.. A patient population and a control population were studied. The former consisted of 18 individuals, age range 50-75 years, with a primary histological diagnosis of prostate adenocarcinoma that were divided into two equal groups of 9 patients each. The control population consisted of 40 normogonadic healthy males aged between 23 and 77 years (average age 43). The first group was treated with oral bicalutamide with a daily dose of 150 mg, while the second group was treated with an intramuscular injection of 11.25 mg of leuprorelin every three months. Total ghrelin was measured with a radio immunological direct method using Phoenix's ghrelin human RIA kit. Intra-assay variance was 8.2% and inter-assay variance was 11.4% . Acylated-ghrelin was measured by applying an extraction method using C18 columns followed by radio immunological dosage with antibody and peninsula tracer. Intra-assay variance was 6.1% and inter-assay variance was 8.7% . All other blood parameters were analysed at the central laboratory of the S. Orsola-Malpighi Polyclinic in Bologna. PSA and testosterone were used to assess response to treatment. The PSA monitoring was achieved with a chemio-luminescence assay method (Roche Modular analytics E 170). Free T was also measured using a direct RIA kit (Diagnostic Systems Laboratories, Inc.).. In the four months during which patients underwent pharmacological treatment, testosterone values varied significantly (p<0.05) in both groups. No variations (p>0.05) were found for ghrelin, acylated-ghrelin and insulin.. It is concluded that in patients with prostate neoplasms there is no correlation between the variations of circulating levels of ghrelin and those of testosterone.

Topics: Acylation; Adenocarcinoma; Adult; Aged; Ghrelin; Humans; Insulin; Leuprolide; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

The incidence of, and mortality from, prostate cancer (PCa) has increased in Asian countries over the past decades, partly due to a change in dietary habits. Recent reports have revealed differences in the molecular basis of PCa among people of differing racial or ethnic backgrounds. PCa xenograft models established from Asian patients would be useful for understanding the basis of PCa in Asian populations; we therefore established and characterized a novel PCa xenograft model, JDCaP, from a metastatic skin lesion of a Japanese hormone-refractory prostate cancer (HRPC) patient.. Skin metastatic tissue derived from poorly differentiated prostatic adenocarcinoma in a 61-year-old Japanese male was transplanted to nude mice and JDCaP was established by serial passage. Expression of androgen receptor (AR) and prostate-specific antigen (PSA) was evaluated by immunohistochemistry and the AR sequence was analyzed. Hormone sensitivity of JDCaP was investigated in vivo by orchiectomy followed by administration of steroid hormones, including testosterone, estradiol, progesterone, and hydrocortisone. Therapeutic effects of leuprorelin acetate, bicalutamide, flutamide, diethylstilbestrol (DES), and estradiol were investigated.. JDCaP expressed wild-type AR and PSA and showed androgen dependence. Only testosterone administration maintained tumor proliferation after orchiectomy. Administration of leuprorelin acetate, bicalutamide, and flutamide inhibited tumor growth. DES and estradiol also demonstrated significant antitumor effects.. JDCaP expresses wild-type ARs and exhibits androgen dependence despite its origin from a HRPC patient. The model may be useful to elucidate the molecular basis of PCa in Asian populations and to develop prevention and therapeutic strategies.

Topics: Adenocarcinoma; Animals; Antigens, Neoplasm; Antineoplastic Agents, Hormonal; Asian People; Diethylstilbestrol; Humans; Leuprolide; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; Neoplasm Transplantation; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Receptors, Androgen; Skin Neoplasms; Specific Pathogen-Free Organisms; Transplantation, Heterologous

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Agents, Hormonal; Biopsy; Drug Eruptions; Humans; Injections; Leuprolide; Male; Patch Tests; Prostatic Neoplasms

A 74-yr-old man with prostatic adenocarcinoma underwent magnetic resonance 1H-spectroscopic imaging (1H-MRSI) of the prostate. Based on the results, he was treated with combination therapy using complete androgen blockade (leuprorelin acetate 3.75 mg every 4 wk plus bicalutamide 50 mg daily) and a somatostatin analogue (lanreotide acetate 60 mg every 4 wk). Serum prostate-specific antigen and chromogranin A levels steadily decreased over a 12-mo follow-up period, at which time the patient is alive without disease progression and with a complete objective and symptomatic response.

Topics: Acromegaly; Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents; Diagnosis, Differential; Drug Therapy, Combination; Follow-Up Studies; Humans; Leuprolide; Magnetic Resonance Spectroscopy; Male; Peptides, Cyclic; Prostatic Neoplasms; Severity of Illness Index; Somatostatin; Time Factors

Topics: Adenocarcinoma; Aged, 80 and over; Breast Neoplasms, Male; Fertility Agents, Female; Genes, BRCA2; Humans; Leuprolide; Male; Mutation; Prostatic Neoplasms

A 63-year-old man with a T1c adenocarcinoma of the prostate, Gleason score of 7 (4+3), and a pretreatment prostate-specific antigen (PSA) level of 9.5 ng/mL was treated with external-beam radiation therapy (45 Gy) and 2 magnetic resonance imaging-guided high-dose rate brachytherapy boosts (10 Gy each.) The patient also received neoadjuvant, concurrent, and adjuvant hormonal treatment with leuprolide for 7 months total. Without any further intervention the patient had 2 separate and prolonged PSA increases and decreases 12-35 months after therapy. His PSA nadir was <0.2 ng/mL and rose slowly over several months to 4.2 ng/mL, resolved, and then rose 2.3 ng/mL before again slowly resolving. After prostate irradiation, many patients experience a transient rise in serum PSA levels and a subsequent decline without any treatment. This is known as a PSA "bounce" or "bump." Some patients experience a second transient rise in PSA levels after irradiation. To our knowledge, this case report is the first documentation of a second PSA bump in a patient treated with external-beam radiation therapy and high-dose rate boost therapy and provides context to address concerns and therapeutic decisions confronting physicians and patients.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Brachytherapy; Follow-Up Studies; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Radiotherapy, Conformal; Treatment Outcome

Androgen deprivation therapy (ADT) is a commonly used treatment for metastatic prostate cancer. A 78-year-old patient with metastatic prostate cancer had transfusion-dependent anemia develop while on ADT. The patient also had hereditary hemorrhagic telangiectasia (HHT), with chronic gastrointestinal blood loss. Blood transfusions were required every 3 weeks for 4 months to keep hemoglobin levels above 8 g/dL, despite discontinuation of ADT. The anemia, which had been well managed with iron therapy before ADT, was worsened by the loss of bone marrow-stimulating testosterone effects. The case highlights testosterone's important role in erythrocyte production. Practitioners should monitor hemoglobin levels in patients undergoing ADT.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anemia; Antineoplastic Agents, Hormonal; Blood Transfusion; Gastrointestinal Hemorrhage; Hemoglobins; Humans; Leuprolide; Male; Prostatic Neoplasms; Telangiectasia, Hereditary Hemorrhagic

We report the case of a T3 prostate cancer in a 70-year-old white man. Hormone therapy represents a prominent branch in the treatment of locally advanced and metastatic prostate cancer. Gonadotropin-releasing hormone agonists have been proven to have a double effect on androgen metabolism: an initially stimulating, followed by an inhibitory, effect on the pituitary gland. This phenomenon may be noxious in the case of gonadotroph adenoma, with subsequent symptoms of intracranial hypertension. Gonadotropin-releasing hormone antagonists (abarelix), by avoiding the flare-up reaction, might be used in such instances.

Topics: Adenocarcinoma; Adenoma; Aged; Antineoplastic Agents, Hormonal; Biopsy; Diagnosis, Differential; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Pituitary Neoplasms; Prostatic Neoplasms; Tomography, X-Ray Computed

We report a case in a 70-year-old patient indicated to have a metastatic lesion from a chest X-ray taken during a medical examination. His blood prostatic specific antigen level was very high at 100 ng/ml (normal, less than 4.0 ng/ml). Palpation of the prostate disclosed enlargement to hen's egg size with an irregular surface and indurations bilaterally. Transrectal sextant needle biopsy of the prostate was performed, revealing moderately differentiated adenocarcinoma. Computed tomography (CT) scan and bone scintigraphy showed intrapelvic lymphnode adenopathy and metastasis to the right pubic bone. Under a diagnosis of stage D2 prostate cancer, we initiated endocrine therapy (luteinizing hormone-releasing hormone analogue depot every 4 weeks and bicalutamide). Androgen blockage was very effective and after 6 months, the PSA level had decreased markedly to below 0.2 ng/ml. Sixteen months later, pulmonary metastasis completely disappeared. He is currently free from recurrence and progressing well.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Drug Administration Schedule; Humans; Leuprolide; Lung Neoplasms; Male; Neoplasm Staging; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Tomography, X-Ray Computed; Tosyl Compounds

Gonadotropin-releasing hormone (GnRH) agonists have become the treatment of choice for locally advanced and metastatic prostate cancer. We report a case of prostate cancer in which this treatment led to severe symptoms of intracranial hypertension due to the concomitant presence of an asymptomatic functional pituitary adenoma. A 70-year-old white man was initially evaluated for a multifocal adenocarcinoma, Gleason score 6 (3+3) with perineural invasion suggesting an extracapsular extension. A conformational external beam radiation (74 Gy) with a concomitant GnRH agonist (leuprolide) was initiated. Almost 10 days after the administration of leuprolide the patient complained of visual disturbance, diplopia and other symptoms of intracranial hypertension. Magnetic resonance imaging (MRI) of the brain demonstrated a large sella mass lesion. To relieve the patient's symptoms, a transsphenoidal subtotal tumorectomy was necessary. The histopathological examination revealed an invasive gonadotroph pituitary adenoma. Two years later, there is no sign of progression either on his prostatic disease (prostate-specific antigen of 0.21 ng/mL) or on his pituitary disease (FSH, 4.7 UI/L, LH, 3.1 UI/L and total testosterone, 627 ng/dL) with values of the hypothalamic-pituitary axis in the normal range. We advocate that a high index of suspicion of pituitary tumor must be considered in any case of intracranial hypertension following the administration of GnRH agonist. Abarelix could have a place in such cases.

Topics: Adenocarcinoma; Adenoma; Aged; Antineoplastic Agents, Hormonal; Diagnosis, Differential; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Neoplasms, Multiple Primary; Pituitary Neoplasms; Prostatic Neoplasms; Tomography, X-Ray Computed

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 effects of leuprorelin acetate, a luteinizing hormone-releasing hormone agonist (LHRH-A), on prostate carcinogenesis in probasin/SV40 Tag transgenic rat was investigated. Fifteen weeks after administration of 0.28 and 2.8 mg/kg leuprorelin, prostate weights and serum testosterone levels were significantly decreased compared to values for transgenic controls. Histopathological findings revealed that the incidence of prostatic adenocarcinomas was significantly reduced in ventral, dorsal and lateral lobes of the prostate, correlating with decreased expression of SV40 Tag oncoprotein as well as inhibition of DNA synthesis and proliferation of epithelial cells in neoplastic lesions of the ventral prostate. Microarray analysis further showed leuprorelin acetate to significantly inhibit testicular steroidogenesis, suppressing the expression of SV40 Tag oncoprotein and altering the expression of a large number of genes which might be involved in the inhibition of prostate cancer progression in this rat model.

Topics: Adenocarcinoma; Androgen-Binding Protein; Animals; Animals, Genetically Modified; Antigens, Polyomavirus Transforming; Antineoplastic Agents, Hormonal; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Immunohistochemistry; Leuprolide; Luteinizing Hormone; Male; Oligonucleotide Array Sequence Analysis; Prostate; Prostatic Neoplasms; Rats; Receptors, Androgen; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Seminal Vesicles; Testosterone

The concept of a prostate-specific antigen (PSA) "nadir" has been used as a predictive marker for treatment success in patients treated with radiotherapy for localized prostate carcinoma. However, this approach is not applicable in patients who are concomitantly treated with short-term hormonal therapies. To address this, the authors sought to develop a new predictive marker in such patients after prostate brachytherapy (BT).. Between March 1997 and November 2002, 194 men with clinical Stage T1A-T3N0M0 prostate carcinoma (according to the 1992 International Union Against Cancer/American Joint Committee on Cancer TNM classification system) were treated with interstitial palladium (103Pd3) BT and androgen ablation therapy with or without external beam radiotherapy (EBRT). Based on tumor characteristics, 127 patients received an antiandrogen, finasteride, and BT whereas 67 received an antiandrogen, leuprolide, and EBRT followed by a BT boost. Hormonal therapy was initiated 2-3 months before any radiotherapy for a total duration of 8-9 months. Follow-up included physical examination and determining the PSA level at 3-month intervals. Postoperative serum testosterone was evaluated in preoperatively potent patients with erectile dysfunction > 6 months after therapy. A PSA level < or = 0.06 ng/mL or < or = 0.20 ng/mL detected during a 6-12-month window after the implant were evaluated as predictors of biochemically disease-free survival (DFS), defined as the time to a PSA level > or = 1.0 ng/mL.. Of the 194 patients, 163 were available for analysis. The median length of follow-up was 48 months. In those patients with a PSA level < or = 0.20 ng/mL at 6-12 months, the DFS at 48 months after the implant was 96% (95% confidence interval [95% CI], 91-99%) compared with the remainder of the patients, whose DFS decreased to 80% (95% CI, 65-89%) (P < 0.001). When a PSA level < or = 0.06 ng/mL was used as an indicator, the 48-month DFS was 99% (95% CI, 91-100%) compared with that for patients with a PSA level > 0.06 ng/mL, in whom the DFS was 85% (95% CI, 74-92%) (P = 0.004). Furthermore, because testosterone levels may occasionally remain low after the cessation of luteinizing hormone-releasing hormone agonist therapy and result in erectile dysfunction and an artificially low PSA level, the authors reviewed the serum testosterone levels in 23 patients who were so treated and were experiencing erectile dysfunction. None had PSA values below the lower limit of normal.. A PSA level < or = 0.20 ng/mL or < or = 0.06 ng/mL measured at 6-12 months after BT appears to be a useful predictive marker for detecting early success in patients with prostate carcinoma who are treated with neoadjuvant androgen ablation and BT. These markers may be used to identify those patients who are at an increased risk of biochemical failure and may be useful in stratifying patients for closer follow-up, long-term adjuvant therapies, or clinical trials. A longer follow-up period will be needed to verify whether these are predictive of long-term cancer control.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Brachytherapy; Combined Modality Therapy; Enzyme Inhibitors; Finasteride; Humans; Leuprolide; Male; Neoadjuvant Therapy; Neoplasm Staging; Palladium; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radioisotopes; Risk Factors; Survival Rate; Testosterone; Treatment Outcome; Ultrasonography, Interventional

We report a case of interstitial pneumonitis induced by bicalutamide and/or leuprorelin acetate given as therapy for prostate cancer, in which the pneumonitis was successfully managed by steroid treatment. Steroids were given promptly on the day following onset of pneumonitis, and the patient (72 years old) recovered almost completely within one and a half months. Interstitial pneumonitis, induced by hormone treatment given for prostate cancer, is a reversible condition and a quick diagnosis followed by prompt, proper treatment is important to ensure a successful recovery. The patient had been free of interstitial pneumonitis for 14 months, but died of pneumothorax.

Topics: Adenocarcinoma; Aged; Anilides; Anti-Inflammatory Agents; Antineoplastic Agents, Hormonal; Bone Neoplasms; Humans; Leuprolide; Lung Diseases, Interstitial; Male; Methylprednisolone Hemisuccinate; Nitriles; Prostatic Neoplasms; Tosyl Compounds

To evaluate, in a pilot study, the tumor control outcomes of our approach and define the pretreatment characteristics that predict a response to therapy. Patients with advanced clinically localized prostate cancer have a high likelihood of prostate-specific antigen (PSA) failure 3 to 5 years after initial treatment. We adopted trimodality therapy (neoadjuvant and adjuvant androgen ablation, external beam radiotherapy [RT], and a brachytherapy boost) to augment biochemical disease-free survival in this patient population.. From 1997 to 2000, 93 patients with clinical Stage T2b or greater, or PSA level greater than 10 ng/mL, or Gleason score 7 or greater were treated with external beam RT followed by palladium-103 brachytherapy. Two to three months before external beam RT, an 8 to 9-month regimen of leuprolide and an oral antiandrogen was initiated. Patients were followed up at 3 to 4-month intervals with PSA determination and digital rectal examination. Perineural invasion, the percentage of cancer in biopsy cores, pretreatment PSA level, clinical T stage, and Gleason score were analyzed as prognostic factors for biochemical failure defined by both the American Society for Therapeutic Radiology and Oncology (ASTRO) criteria and PSA level greater than 0.2 ng/mL.. The median length of follow-up was 45 months. The overall probability of biochemical failure using a PSA level greater than 0.2 ng/mL at 4 years was 79% (95% confidence interval 69% to 89%). With the ASTRO criteria, the overall failure rate at the same point was 77% (95% confidence interval 68% to 87%). Gleason score (P = 0.07) showed a trend toward predicting biochemical failure using the PSA level greater than 0.2 ng/mL criterion.. Trimodality RT offers excellent tumor control in patients with poor prognosis who often relapse early. Longer follow-up will be important to determine whether these results are durable over time.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Brachytherapy; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Humans; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Palladium; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radioisotopes

GnRH analogs have antiproliferative and/or apoptotic effects on prostate cancer cells. Also, neurotrophin receptors TrkA and p75 have been reported in normal prostate suggesting a role in the gland growth control. In prostate cancer, TrkA receptors seem to be overexpressed and p75 receptors show a decreased expression. These changes in neurotrophin receptors may be related with unbalanced growth in malignant cells. In the present study we investigate the effects of GnRH analogs (leuprolide and cetrorelix) on the expression of TrkA and p75 neurotrophin receptors in primary cultures of human prostate cancer cells.. Tissue was obtained from radical prostatectomies due to prostate adenocarcinoma. Cells were isolated after sequential enzyme digestion and cultured in defined media. Nerve growth factor (NGF) receptors in untreated cultures were estimated by immunofluorescence. Cultures were treated with leuprolide (agonist) or cetrorelix (antagonist) and expression of TrkA and p75 receptors were evaluated by semi quantitative RT-PCR (polymerase chain reaction) and western blot. Cell proliferation was estimated by MTT method and apoptosis through COMET assay.. Both leuprolide and cetrorelix induced a significant increase in p75 receptor gene and protein expression at a concentration that induce apoptosis and decrease proliferation. TrkA receptors showed no changes in presence of GnRH analogs.. GnRH analogs, leuprolide, and cetrorelix, change the ratio between neurotrophin receptors TrkA and p75 by increasing gene and protein expression of p75 receptor. Considering that TrkA receptor is related with proliferation and p75 with apoptosis, we suggest that our findings may explain, in part, the effect of GnRH analogs on prostate cancer growth.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Apoptosis; Blotting, Western; Cell Proliferation; Comet Assay; Epithelial Cells; Formazans; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Prostatic Neoplasms; Receptor, Nerve Growth Factor; Receptor, trkA; Receptors, Nerve Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; Tetrazolium Salts

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Humans; Insulin Resistance; Leuprolide; Male; Nitriles; Prostatic Neoplasms; Tosyl Compounds

Pure red cell aplasia (PRCA) is characterized by anemia with reticulocytopenia but with normal leukocyte and platelet counts, and a bone marrow with a selective absence of erythroid precursor cells. Drug-induced PRCA is a rare secondary form of PRCA, and is usually acute and fully reversible by the withdrawal of the causative drugs. We report a rare case of PRCA in a prostate cancer patient treated with combined androgen blockade (CAB) consisted of leuprolide acetate as a luteinizing hormone-releasing hormone agonist and chlormadinone acetate as an antiandrogen. This case demonstrated that these drugs could be a cause of PRCA, and suggests that regular close monitoring for anemia is needed in prostate cancer patients treated with these drugs.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chlormadinone Acetate; Drug Therapy, Combination; Erythrocyte Transfusion; Humans; Leuprolide; Male; Prostatic Neoplasms; Radiotherapy, Adjuvant; Red-Cell Aplasia, Pure

Once metastatic, prostate cancer was regarded as a systemic disease that is not amenable to surgical therapy. We present a case of a solitary pulmonary recurrence of prostate cancer after radical prostatectomy that was resected, resulting in 12 years of biochemical remission without additional therapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Combined Modality Therapy; Cough; Disease-Free Survival; Dyspnea; Flutamide; Follow-Up Studies; Humans; Leuprolide; Lung Neoplasms; Male; Neoplasm Proteins; Pneumonectomy; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Remission Induction

To better understand bone metabolism and predict bone loss in treatment using gonadotropin-releasing hormone agonist for patients with prostate cancer.. The changes in bone mineral density and blood levels of bone metabolism markers and the level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen, a specific marker of bone resorption, and carboxy-terminal pro-peptide of human type I procollagen, a specific marker of bone formation, were examined in 27 consecutive patients with prostate cancer without bone metastasis.. After 2 years of gonadotropin-releasing hormone treatment, the bone mineral density was significantly lower (median 0.937 g/cm2) than before treatment. Pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen began to increase significantly 6 months after the start of treatment (3.0 to 8.3 ng/mL, median 4.6, at baseline versus 3.4 to 8.2 ng/mL, median 5.2, after 6 months). Carboxy-terminal pro-peptide of human type I procollagen began to show a significant rise 1 year after the start of treatment (from 72.8 to 221.5 ng/mL, median 102.0, at baseline to 82.7 to 293.4 ng/mL, median 132.0, at 1 year).. Functional coupling between bone resorption and formation was noted, and a decrease in bone mass, even in men, owing to androgen deficiency, was biochemically demonstrated. Fluctuations in these two bone metabolism markers preceded the decrease of bone mineral density. Therefore, these markers might be a predictor of bone loss.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Density; Bone Remodeling; Bone Resorption; Collagen Type I; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Peptide Fragments; Peptides; Procollagen; Prostatic Neoplasms; Testosterone

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Biopsy; Combined Modality Therapy; Disease-Free Survival; Drug Resistance, Neoplasm; Humans; Leuprolide; Male; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radionuclide Imaging; Radiotherapy, Conformal; Spinal Neoplasms; Tomography, X-Ray Computed

We describe a prostate cancer patient whose initial symptom was intermittent double vision. Intracranial magnetic resonance imaging demonstrated a pituitary mass extending to the cavernous sinus, which caused the double vision. After hormonal therapy for prostate cancer, the pituitary mass disappeared, and double vision was completely resolved without local therapy for the brain. In the 19 months of follow-up after hormone treatment, the prostate cancer remained stable, and the patient remained neurologically intact.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Chlormadinone Acetate; Diplopia; Humans; Leuprolide; Magnetic Resonance Angiography; Male; Pituitary Neoplasms; Prostatic Neoplasms; Remission Induction

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Electromyography; Humans; Leuprolide; Male; Muscular Diseases; Prostatic Neoplasms; Time Factors

Topics: Adenocarcinoma; Graft Rejection; Heart Transplantation; Hormone Replacement Therapy; Humans; Leuprolide; Male; Prostatic Neoplasms; Risk Factors; Stroke Volume; Testosterone; Ventricular Function, Left

Prostate carcinoma presenting initially as multiple pulmonary nodules in an asymptomatic patient without previous prostate carcinoma is unusual. Whether the incidence of prostate carcinoma is significantly increased in patients treated previously for germ cell tumors is unclear. We report such a patient, who responded to combination androgen blockade therapy.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cisplatin; Combined Modality Therapy; Etoposide; Flutamide; Humans; Leuprolide; Lung Neoplasms; Male; Neoplasms, Germ Cell and Embryonal; Neoplasms, Multiple Primary; Neoplasms, Second Primary; Orchiectomy; Postoperative Complications; Prostatic Neoplasms; Radiography; Testicular Neoplasms

Macro CK (creatine kinase) as a reason for high CK values has been known since 1979. Even in the era of troponin determination for the diagnosis of myocardial infarction, an elevated CK value can still cause confusion, especially as CK-MB rises earlier than troponin. The case report should remind us of this often forgotten differential diagnosis of elevated CK.. A 73-year-old patient was treated with leuprorelin hormone therapy for prostate cancer (stage pT1c G2). In addition, he received percutaneous radiation therapy of the prostate and high-dose-rate brachytherapy twice with 10 Gy each. Close to 1 year later, he complained for the first time of dyspnea on exertion and thoracic tightness. Serum CK was 232 U/l, and CK-MB 62 U/l, which was confirmed by several controls. Troponin T test was negative, and GOT, GPT, LDH, and PSA were all within the normal range. Acute myocardial infarction was ruled out on clinical grounds and by six sequential ECGs. Subsequently, the patient remained without further cardiac complaints and in good condition. Isoenzyme electrophoresis finally solved the problem and revealed CK-BB-IgG complex type 1 (macro CK-1).. High CK-MB values in cardially healthy patients should remind us of the possibility of macro CK which is seen in approximately 0.5% of cases and should be included in the differential diagnosis.

Topics: Adenocarcinoma; Aged; Antigen-Antibody Complex; Antineoplastic Agents, Hormonal; Brachytherapy; Chest Pain; Combined Modality Therapy; Creatine Kinase; Creatine Kinase, MB Form; Diagnosis, Differential; Electrocardiography; Humans; Immunoglobulin G; Isoenzymes; Leuprolide; Macromolecular Substances; Male; Myocardial Infarction; Neoplasm Staging; Prostatic Neoplasms; Radiotherapy, Adjuvant

Malignancies may cause cholestatic jaundice through well-recognized mechanisms (e.g., bile duct obstruction or widespread hepatic infiltration). Paraneoplastic syndromes associated with malignancy, particularly with renal cell carcinoma (Stauffer's syndrome) and malignant lymphoproliferative diseases, can induce a reversible form of cholestasis through an unclear pathogenetic mechanism. Prostate cancer presenting initially with cholestatic jaundice without any obvious cause (i.e., obstruction or infiltration) has been reported in 2 cases in the medical literature. We report a patient who presented with pruritus and cholestatic jaundice. During the diagnostic work-up, prostate cancer was diagnosed. Conjugated bilirubin and alkaline phosphatase levels were increased markedly with modest increases of gamma-glutamyltranspeptidase and transaminase levels. The results of appropriate investigations performed during the patient's hospitalizations indicated no evidence of hepatic metastases or extrahepatic biliary obstruction. After treatment with flutamide and leuprolide, the patient's symptoms and the laboratory abnormalities reversed rapidly. We regard the cholestatic jaundice of this patient as part of a paraneoplastic syndrome; the cause of cholestasis remains an enigma. Patients with unexplained cholestasis should be investigated for malignancies, including prostate cancer.

Topics: Adenocarcinoma; Aged; Alkaline Phosphatase; Antineoplastic Agents, Hormonal; Bilirubin; Biomarkers, Tumor; Cholangiopancreatography, Endoscopic Retrograde; Diagnosis, Differential; Flutamide; gamma-Glutamyltransferase; Humans; Jaundice, Obstructive; Leuprolide; Male; Paraneoplastic Syndromes; Prostatic Neoplasms; Pruritus; Tomography, X-Ray Computed; Transaminases

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Diagnosis, Differential; Granuloma; Humans; Injections; Leuprolide; Male; Neoplasm Recurrence, Local; Prostatic Neoplasms; Skin Diseases; Skin Neoplasms

Disseminated intravascular coagulation (DIC) revealing a prostatic adenocarcinoma is rare. Most of the case are limited to biological abnormalities. We report a case of a 73 year old man with metastatic prostatic carcinoma and CIVD. The patient consulted for epistaxis and ecchymosis with thrombocytopenia and low coagulate factors. The prostatic specific antigen was 2200 ng/ml and fine needle aspiration of bone marrow biopsy detected metastatic cells. The patients received hormonotherapy, heparine and antithrombine III with a good follow up. About this case, we discuss the management of the patient with metastatic prostatic cancer and CIVD.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anticoagulants; Antithrombin III; Bone Neoplasms; Disseminated Intravascular Coagulation; Fibrinolysis; Follow-Up Studies; Heparin; Humans; Injections, Subcutaneous; Leuprolide; Male; Prostatic Neoplasms; Sternum; Time Factors

The effect of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy (RP) on pathological downstaging of prostate cancer and biochemical relapse of serum prostate specific antigen (PSA) level was evaluated.. Twenty selected patients with prostate cancer, who were treated with hormonal therapy and demonstrated biochemical downstaging by reduction of PSA prior to RP and bilateral pelvic node dissection at the Tohsei National Hospital between January 1997 and August 2001, are reported on. The complete RP specimens of these 20 men were used for accurate evaluation of the pathological stage. All 20 patients received NHT; ten patients were treated with leuprolide plus flutamide and 10 received leuprolide plus chlormadinone acetate (CMA).. Decreases in serum PSA values were demonstrated from a pre-hormonal average of 49.7 ng/ml to an average of 0.52 ng/ml after NHT. Of the three clinical stages, A2-C, for cancer patients, two of the 20 patients had stage A2, two had stage B1, nine had stage B2, and seven had stage C. Of the 20 patients with biochemical downstaging, two had pathological stage B1, seven had pathological stage B2, eight had pathological stage C, and three had positive pelvic lymph nodes. Ten (50%) of the 20 patients were reported to have positive surgical margins. Seminal vesical extension was observed in two cases, and penetration was not observed. Positive nodes were identified in three (15%) patients. Among the seven clinical stage C patients, one had pathological stage B1 disease and two had pathological stage B2. Four of nine patients with clinical stage B2 prostatic cancer had pathological stage C disease. The actuarial incidence of a rising PSA at 3 years for the leuprolide plus CMA group was 28.9% compared with 37.5%for the group receiving leuprolide plus flutamide. The cases of biochemical relapse did not necessarily indicate a high stage and had no tendency to be high for baseline PSA level, positive margin rates or Gleason scores.. A significant decrease in the rate of penetration could be observed after NHT, though it was not so effective for pathological downstaging, and changes in the preoperative PSA level did not predict those patients who might have a favorable result.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chlormadinone Acetate; Flutamide; Humans; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

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

Hormone therapy with leuprolide acetate (Lupron) is frequently used to treat prostate cancer, a common malignancy expected to be diagnosed in >180,000 men in the United States this year. In addition, testosterone supplementation is frequently recommended for adult men with reduced libido or impotence and decreased serum levels of testosterone. Although these hormone therapies are generally considered benign, we describe 3 cases of acute cardiac rejection temporally associated with the use of these drugs in men who have undergone cardiac transplantation. To our knowledge, this is the first such description of this phenomenon in the literature.

Topics: Acute Disease; Adenocarcinoma; Aged; Graft Rejection; Heart Transplantation; Hormone Replacement Therapy; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Risk Factors; Stroke Volume; Testosterone; United States; Ventricular Function, Left

We assessed the degree of prostate downsizing using androgen deprivation, and determined its relation to clinical and pathological variables.. From June 1994 to January 2000, 107 patients with prostate cancer received androgen deprivation before interstitial brachytherapy at our hospital. All charts were reviewed for clinical, pathological and treatment related variables. Prostate volume was measured using transrectal ultrasound. All variables were analyzed with regard to the degree of prostate downsizing.. Mean percent volume reduction of the prostate was 33% after a 3.7-month average duration of androgen deprivation. Larger prostate volume before androgen deprivation and longer deprivation duration statistically correlated with mean percent volume reduction. Simple linear and multiple regression analyses revealed that these 2 variables remained significant predictors of percent volume reduction. Subgroup analysis indicated that a significant difference was seen in patients who received androgen deprivation with luteinizing hormone releasing hormone agonists alone versus those who received treatment with total androgen blockade (luteinizing hormone releasing hormone agonists plus antiandrogens 30% versus 35%, p = 0.04), and when prostate volume before androgen deprivation was less than 50 cc versus larger volumes (30% versus 35%, p = 0.01). Of patients with an initial prostate volume of greater than 50 cc 82% achieved a volume of less than 50 cc after androgen deprivation therapy.. Androgen deprivation therapy before brachytherapy is a method of downsizing the prostate to overcome anatomical limitations, including larger gland volume and pubic arch interference.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Brachytherapy; Combined Modality Therapy; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostate; Prostatic Neoplasms; Regression Analysis; Ultrasonography

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Disease Progression; Drug Resistance, Neoplasm; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Androgen Antagonists; Antineoplastic Agents, Hormonal; Estradiol; Flutamide; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Testosterone

After the initiation of androgen suppression in men with prostate cancer, the serum prostate-specific antigen (PSA) level generally declines. A subsequent PSA rise during that suppression usually reflects the presence of a significant component of hormonally refractory prostate cancer. We report a patient with a rising PSA level and elevated testosterone level after depot leuprolide in whom the PSA level subsequently declined with administration of bicalutamide.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anilides; Antineoplastic Agents; Delayed-Action Preparations; Humans; Injections, Intramuscular; Leuprolide; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Tosyl Compounds; Treatment Outcome

Topics: Adenocarcinoma; Adult; Antineoplastic Agents, Hormonal; Follow-Up Studies; Humans; Leuprolide; Male; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms; Treatment Failure; Treatment Outcome

Topics: Adenocarcinoma; Anticarcinogenic Agents; Carotenoids; Drug Resistance, Neoplasm; Humans; Leuprolide; Lycopene; Male; Middle Aged; Prostatic Neoplasms

We report here a case of a patient affected by endometrial cancer and treated primarily with leuprolide, the surgical approach being unfeasible due to her compromised conditions. The therapy was continued for more than 6 years, and no progression of the disease was observed. During this period, some histological and immunohistochemical evaluations of the tumour (morphology, grading, proliferation and apoptotic index, E-cadherin expression) were performed. Furthermore, the expression of m-RNA for luteinizing-hormone releasing hormone (LHRH) receptors was determined. The results showed a discrepancy between some biological parameters of the tumour and its clinical characteristics. In fact, despite features suggestive of a progression of the cancer (such as the increase of both tumour grading and proliferating capacity (MIB-1), and a fall in the reparative process (appearance of mutated p53, reduced expression of both bcl-2 and c-erb-2) being detected, neither local invasion nor metastatic lesions were clinically observed. This discrepancy might be due to the maintenance of high levels of E-cadhezin. Moreover, since this tumour was shown to express mRNA for LHRH receptors, new evidence is provided about the favourable impact of LHRH analogue treatment in patients affected by endometrial cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Disease Progression; Disease-Free Survival; Endometrial Neoplasms; Female; Humans; Leuprolide; Neoplasm Proteins; Receptors, LHRH; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

We report endometrial adenocarcinoma in two patients shortly after suspending GnRH-agonist treatment for menometrorrhagia and uterine fibromata.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Female; Humans; Injections, Intramuscular; Leiomyoma; Leuprolide; Metrorrhagia; Middle Aged; Myometrium; Neoplasms, Second Primary; Triptorelin Pamoate; Uterine Neoplasms

Permanent androgen ablation has been the mainstay of treatment for advanced prostate cancer. However, the favorable outcome seen in recent pilot studies of intermittent androgen ablation raises the possibility of overtreatment.. This study included 35 Japanese men with advanced prostate cancer. Initial androgen ablation continued for 2 months after PSA levels decreased to <4.0 ng/ml, then was withdrawn. Androgen ablation was reinstituted 2 months after PSA reached levels >10 ng/ml, when indicated clinically or on patient request. Cycling continued until androgen independence was reached.. Mean follow-up was 21.0 months, representing an average of 2.5 cycles. Nine patients developed androgen independence at an average of 16.0 months following androgen ablation; three of these have died. Six of the nine patients with early biochemical progression had elevated alkaline phosphatase levels at entry; five of these exhibited a flare in alkaline phosphatase activity after initiation of androgen ablation. Mean bone mineral density (BMD) in the lumbar spines of 17 patients was 81.5 mg/cm3 at 23 months following therapy. The BMD of 10 of these patients was normal for their age. Four patients suffered bone fractures, none pathological.. Intermittent androgen ablation may be an option for patients with advanced prostate cancer and may be especially beneficial for those with initially low BMD levels. Patients with elevated alkaline phosphatase levels at entry or a flare in its activity may not be ideal candidates. Whether prolonging time to androgen independence will provide benefit remains to be investigated in a randomized, prospective study.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Disease Progression; Drug Administration Schedule; Flutamide; Follow-Up Studies; Fractures, Bone; Goserelin; Humans; Leuprolide; Lumbar Vertebrae; Male; Middle Aged; Pilot Projects; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Survival Rate; Testosterone; Treatment Outcome

Patients scheduled for prostatectomy often receive androgen deprivation therapy to make malignant tumors more amenable to resection and improve the postoperative course. These hormonal therapies may significantly alter the histomorphology of carcinoma of the prostate detected on subsequent needle biopsies.. Needle specimens were obtained from resected prostates harboring biopsy-proven carcinoma previously treated with leuprolide. The tissue was examined by light microscopy to note architectural and cytologic characteristics.. A high proportion of treated carcinomas had an atrophic, infiltrative appearance. Nuclear and nucleolar enlargement were consistently observed. Macronucleoli, blue-tinged mucin, and intraluminal pink amorphous material was frequently identified.. The markedly atrophic nature of the cells and glands may result in either overgrading of prostate carcinoma or failure to recognize the more subtle patterns of this malignant neoplasm. It is imperative that clinicians convey a history of hormone treatment to pathologists when core biopsies of the prostate are submitted for histologic evaluation.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Biopsy, Needle; Communication; Humans; Interprofessional Relations; Leuprolide; Male; Middle Aged; Military Medicine; Military Personnel; Pathology, Clinical; Physician's Role; Prostatectomy; Prostatic Neoplasms

To assess the effectiveness of palladium-103 brachytherapy in stage T1 and T2 adenocarcinoma of the prostate.. The charts of 1048 patients treated between 1991 and 1999 with transperineal realtime ultrasound-guided (103)Pd (Theraseed) implants were reviewed to assess the effects on serum prostate specific antigen (PSA) values and tissue (biopsy). Of the 1048 patients, 780 had sufficient data for this report. Preoperative total androgen blockade (leuprolide and flutamide) was used selectively in patients whose prostate size was >50 cc and those whose tumors had a Gleason score of >7.. At 1 year, 86% of the evaluable 766 patients had stable PSA concentration <1.5 ng/mL; at 5 years, 86% of the 166 patients with data available had stable PSA values <1.5 ng/mL. Biopsies were negative in 92% of the patients studied at 2 years. Patients with pretreatment PSA values <10 ng/mL had the best outcomes, and those treated with (103)Pd plus hormone ablation achieved PSA reduction more rapidly than those treated with radioisotope monotherapy. There was one disease-related death; the principal morbidity was short-term bladder and bowel irritation without permanent sequelae. Impotence occurred in approximately 15% of patients, and incontinence occurred in 5% of those who had undergone prior transurethral resection of the prostate.. The technique used in this study proved effective in reducing PSA concentrations to <1.5 ng/mL and in producing negative biopsies 1 and 2 years postoperatively. These results are comparable to those of external-beam radiation therapy and radical prostatectomy while demonstrating a significant reduction in morbidity.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Biopsy; Brachytherapy; Combined Modality Therapy; Flutamide; Humans; Leuprolide; Male; Middle Aged; Palladium; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radioisotopes; Ultrasonography

Fine-needle aspiration of prostatic carcinoma usually yields an acinar carcinoma that is immunoreactive for prostatic-specific antigen (PSA) and prostatic acid phosphatase (PAP). We report on two FNAs of metastatic sarcomatoid prostatic carcinoma that were PSA- and PAP-negative. Our methods included a review of the medical records and pathology results. Both cases presented with elevated serum PSA levels and prostate needle biopsies with Gleason score 8 and 9 tumors, respectively. Both cases developed retroperitoneal/pelvic lymphadenopathy, and fine-needle aspirations were performed. These showed high-grade, sarcomatoid tumors with marked anisonucleosis. Immunocytochemical staining for PSA and PAP was negative in both cases. Clinical and radiologic evaluation failed to reveal any other potential primary sites. Metastatic, sarcomatoid, PSA- and PAP-negative prostatic carcinoma is a rare diagnosis of exclusion that should be considered in the characteristic clinical setting.

Topics: Acid Phosphatase; Adenocarcinoma; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Carcinoembryonic Antigen; Flutamide; Humans; Immunohistochemistry; Keratins; Leuprolide; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Sarcoma

Patients with prostate cancer are treated with neoadjuvant, adjuvant and intermittent androgen deprivation therapy. Prostate specific antigen (PSA) is altered during androgen deprivation therapy, and as a result the prognostic significance and accuracy of PSA values measured before serum testosterone has normalized are questionable because the patient is still effectively on androgen deprivation therapy. We determine the time it takes for serum testosterone to return to normal after withdrawal of androgen deprivation therapy.. Serial serum testosterone was prospectively measured at 3-month intervals in 68 men after withdrawal of androgen deprivation therapy. The number of months to return to normal serum testosterone 270 ng./dl. or greater, was calculated for each patient. Patients were stratified according to duration of androgen deprivation, age and type of luteinizing hormone releasing hormone agonist used.. Median patient age was 71 years (range 46 to 88). Median time to normalization of testosterone was 7 months (range 1 to 58). At 3, 6 and 12 months 28%, 48% and 74% of men had normal serum testosterone, respectively. Serum testosterone took significantly longer to return to normal in patients on androgen deprivation therapy for 24 months or greater compared to those on therapy for less than 24 months (log-rank p = 0.0034). There was no statistical significance based on age or type of luteinizing hormone releasing hormone agonist used.. Androgen deprivation has an effect on serum testosterone that extends beyond the cessation of treatment. Serum testosterone should be measured in all men until normalization. These results should be applied to the interpretation of PSA levels after withdrawal of androgen deprivation therapy. In addition, these data have implications regarding dose scheduling and definition of biochemical (PSA) failure after primary therapy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Testosterone; Time Factors

The indolocarbazole analogue CEP-751 is a potent and selective tyrosine kinase inhibitor of the neurotrophin-specific trk receptors that has demonstrated antitumor activity in nine different models of prostate cancer growth in vivo. In the slow-growing, androgen-sensitive Dunning H prostate cancers, which express trk receptors, CEP-751 induced transient regressions independent of effects on cell cycle. Because androgen ablation is the most commonly used treatment for prostate cancer, we examined whether the combination treatment of CEP-751 with castration would lead to better antitumor efficacy than either treatment alone. For a 60-day period, H tumor-bearing rats received treatment with either castration, CEP-751 (10 mg/kg once a day s.c. for 5 days every 2 weeks), a combination of both, or vehicle. Castration caused tumor regression, followed by tumor regrowth in 4-6 weeks, whereas intermittent CEP-751 treatments resulted in tumor regressions during each treatment, which were followed by a period of regrowth between intermittent drug treatment cycles. Overall, both monotherapies significantly inhibited tumor growth compared with the vehicle-treated control group. However, the combination of castration and concomitant CEP-751 produced the most dramatic results: sigificantly greater tumor regression than either therapy alone, with no signs of regrowth. A related experiment using an orally administered CEP-751 analogue (CEP-701), as the trk inhibitor, and a gonadotrophin-releasing hormone agonist, Leuprolide, to induce androgen ablation demonstrated similar results, indicating that these effects could be generalized to other forms of androgen ablation and other trk inhibitors within this class. In addition, when CEP-701 was given sequentially to rats bearing H tumors, which were progressing in the presence of continuous androgen ablation induced by Leuprolide, regression of the androgen-independent tumors occurred. In summary, these data demonstrate that CEP-751 or CEP-701, when combined with surgically or chemically induced androgen ablation, offer better antitumor efficacy than either monotherapy and suggest that each therapy produces prostate cancer cell death through complementary mechanisms.

Topics: Adenocarcinoma; Administration, Oral; Androgens; Animals; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Carbazoles; Combined Modality Therapy; Drug Screening Assays, Antitumor; Drug Synergism; Furans; Indoles; Injections, Subcutaneous; Leuprolide; Male; Neoplasm Proteins; Neoplasm Transplantation; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Proto-Oncogene Proteins; Rats; Receptor Protein-Tyrosine Kinases; Receptor, trkA; Receptors, Nerve Growth Factor

To determine the change in volume of the prostate as a result of neoadjuvant androgen deprivation prior to prostate implant and in the early postimplant period following transperineal ultrasound guided palladium-103 brachytherapy for early-stage prostate cancer.. Sixty-nine men received 3 to 6 months of androgen deprivation therapy followed by treatment planning ultrasound followed 4 to 8 weeks later by palladium-103 implant of the prostate. All patients had clinical and radiographic stage T1c-T2b adenocarcinoma of the prostate. A second ultrasound study was carried out 11 to 13 days following the implant to determine the change in volume of the prostate as a result of the implant. The prehormonal and preimplant volumes were compared to the postimplant volume to determine the effect of hormones and brachytherapy on prostate volume.. The median decrease in prostate volume as a result of androgen deprivation was 33% among the 54 patients with prostate volume determinations prior to hormonal therapy. The reduction in volume was greatest in the quartile of men with the largest initial gland volume (59%) and least in the quartile of men with smallest glands (10%). The median reduction in prostate volume between the treatment planning ultrasound and the follow-up study after implant was 3%, but 23 (33%) patients had an increase in prostate volume, including 16 (23%) who had an increase in volume >20%; 11 of these patients (16%) had an increase in volume >30%. The time course of development and resolution of this edema is not known. The severity of the edema was not related to initial or preimplant prostate volume or duration of hormonal therapy.. Prostate edema may significantly affect the dose delivered to the prostate following transperineal ultrasound guided brachytherapy. The effect on the actual delivered dose will be greater when shorter lived isotopes are used. It remains to be observed whether this edema will affect outcome.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Brachytherapy; Combined Modality Therapy; Dose-Response Relationship, Radiation; Goserelin; Humans; Iodine Radioisotopes; Leuprolide; Male; Palladium; Prostatic Neoplasms; Radiopharmaceuticals; Ultrasonography, Interventional

Neoadjuvant combination endocrine therapy that uses leuprolide and flutamide may result in various histologic changes in nontumoral and cancerous prostatic tissues. Posttreatment pseudomyxoma ovariilike change in prostatic adenocarcinoma is a distinctive alteration that may be the only evidence of regressed tumor and can be potentially confused with mucinous carcinoma. We studied 53 clinically localized prostatic adenocarcinomas after 3 to 5 months of treatment with leuprolide and flutamide. Alterations in prostatic adenocarcinoma in posttreatment radical prostatectomy specimens were assessed and compared with pretreatment needle biopsies. All radical prostatectomy specimens exhibited previously well-characterized therapy-associated changes in benign and malignant elements. Thirteen (20%) cases exhibited a distinctive alteration not seen in pretreatment needle biopsies that consisted of minute to large pools of extravasated secretions that resembled pseudomyxoma ovarii and that dissected through prostatic stroma with an infiltrative appearance when viewed at low power. Associated recognizable tumor was present in 10 of 13 (77%) of these cases. Secretions were basophilic in routine sections and contained occasional degenerated cells. Rare pancytokeratin positive cells were seen at the secretion/stroma interface with uniformly negative staining for the high molecular weight keratin 34 beta E-12. The secretions were periodic acid-Schiff positive after diastase digestion and were mucicarminophilic and reactive with Alcian blue at a pH of 2.5. These foci comprised < 5% of the tumor in 5 cases and 5-40% in 5 cases. In 3 cases, 1-2 foci < 1.0 mm exhibited the pseudomyxoma ovariilike changes and were the only evidence of treated tumor. There was no correlation between the presence of pseudomyxomalike change and dose/duration of neoadjuvant therapy, postprostatectomy clinical follow-up, original or final Gleason pattern/score, or pathologic stage. Pseudomyxoma ovariilike change consists of extravasated acid mucin, lacks prostatic basal cells, often occurs in intimate association with residual prostatic adenocarcinoma in posttreatment radical prostatectomy specimens, and probably represents tumor regression as a result of tumor cell attrition secondary to androgen ablation.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Female; Flutamide; Humans; Leuprolide; Male; Middle Aged; Myxoma; Ovary; Prostate; Prostatic Neoplasms

Combined androgen blockade using a pure antiandrogen in association with a LHRH agonist or surgical castration is the most logical approach. This paper demonstrated that flutamide combined with leuprorelin acetate produced a significant reduction in the growth rate of Dunning R3327-H prostatic adenocarcinoma. Dunning R3327-H prostatic adenocarcinoma, provided by Dr. Norman H. Altmann (University of Miami, USA) was subcutaneously inoculated into the lateral region of male Copenhagen x Fischer F1 hybrid rat abdomen. The efficacy of the tumor growth rate was evaluated by measuring tumor size at 10 weeks after the inoculation. Flutamide was orally administered for 10 weeks and leuprorelin acetate was subcutaneously administered every 4 weeks. The effective dose of flutamide and leuprorelin acetate was determined in preliminary studies, and the following doses were used in the study; 15 mg/kg for flutamide, 0.1 mg/kg or 0.4 mg/kg for leuprorelin acetate. In combination of flutamide with leuprorelin acetate at 0.1 mg/kg and 0.4 mg/kg, the tumor inhibition was 94% and 97%, respectively. In addition, the weight of accessory sex organs coincided with the antitumor effect. Taking the above results into consideration, combined androgen blockade using flutamide and leuprorelin acetate may have some beneficial effect on prostatic cancer.

Topics: Adenocarcinoma; Androgen Antagonists; Animals; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Cell Division; Drug Administration Schedule; Flutamide; Leuprolide; Male; Organ Size; Prostatic Neoplasms; Rats

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Humans; Imidazoles; Imidazolidines; Leuprolide; Lung Diseases, Interstitial; Male; Prostatic Neoplasms

To assess the effectiveness of palladium 103 (Pd-103) brachytherapy in Stage T1 and T2 adenocarcinoma of the prostate.. Charts of 474 patients treated between 1991 and 1996 with transperineal real-time ultrasound-guided Pd-103 implants were reviewed to assess post-treatment prostate-specific antigen (PSA) levels and follow-up biopsy results. Of 474 patients, 434 had sufficient data for this report. The implant technique used allows precise placement of seeds and accurate dose delivery of the entire prostate. Preoperative neoadjuvant leuprolide (Lupron) and flutamide (Eulexin) were given selectively to reduce prostate size greater than 50 cc and for Gleason grade lesions greater than 7.. Of 434 patients, successful cancer control was demonstrated in 81% of patients by a decrease in PSA levels to less than 1.5 ng/mL at 1 year. Biopsies were negative in 88% of patients 1 year after the procedure and in 89% at 2 years. Analysis of the data suggests that patients with pretreatment PSA levels less than 10 ng/mL had the best outcomes. There were no disease-related deaths; the predominant morbidity was short-term bladder and bowel irritation without permanent sequelae. Incontinence occurred in less than 5% of patients who had undergone prior transurethral resection of the prostate. Impotence occurred in less than 15% of patients.. The technique used in this study proved effective in reducing PSA levels to less than 1.5 ng/mL and in producing negative biopsies 1 and 2 years postoperatively. Results are comparable to external-beam radiation therapy, demonstrating a significant reduction in morbidity.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Ambulatory Care; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Brachytherapy; Chemotherapy, Adjuvant; Flutamide; Follow-Up Studies; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Palladium; Prostate-Specific Antigen; Prostatic Neoplasms; Radiation Injuries; Radioisotopes; Radiopharmaceuticals; Radiotherapy Dosage; Retrospective Studies; Treatment Outcome; Ultrasonography, Interventional

Gonadotropin-releasing hormone (GnRH) receptor-bearing tumors undergo apoptosis in vivo and in vitro with GnRH analogs. We recently showed that GnRH stimulation induces intratumoral expression of the apoptosis-inducing Fas ligand in human reproductive tract tumors. To provide a potential association of Fas/Fas ligand system with the antiproliferative signaling process of GnRH receptor, we evaluated a correlation between the Fas ligand expression and the number of viable cells in two types of GnRH receptor-bearing endometrial carcinomas that differ in Fas content. Surgically removed uterine endometrial carcinomas had been screened for the presence of GnRH receptor and Fas before analyses. Fas ligand protein was characterized by immunoblotting of membrane proteins with the specific antibody. After a lag time of 2 days, incubation with a GnRH analog leuprolide (10 microM) induced significant growth inhibition of the Fas- and GnRH receptor-bearing cells (p<0.01). Time course analysis showed that Fas ligand production, which was already observed at day 2 (p<0.01), precedes the onset of reduction in viable cell number. The stimulatory effect of GnRH on Fas ligand expression and reduction of viable cells revealed dose-dependency. The analog at concentration of 10 microM induced up to 90% reduction in cell number. In contrast, the growth of Fas-negative cells was not affected by the analog, although Fas ligand appeared in response to the GnRH analog (p<0.01). These data demonstrate that the co-presence of Fas could be essential for GnRH to promote antiproliferative action in endometrial cancer cells carrying GnRH receptor. The hormone may act through intratumor Fas and Fas ligand system to induced growth inhibition in GnRH-sensitive tumors.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Cell Death; Endometrial Neoplasms; Fas Ligand Protein; fas Receptor; Female; Humans; Leuprolide; Membrane Glycoproteins; Receptors, LHRH; Tumor Cells, Cultured

Topics: Adenocarcinoma; Adenoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Humans; Hypophysectomy; Leuprolide; Luteinizing Hormone; Male; Neoplasms, Multiple Primary; Pituitary Neoplasms; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Failure

We objectively compare the costs associated with the medical and surgical treatment of metastatic prostate cancer.. We analyzed and compared itemized billing statements for 28 men with metastatic adenocarcinoma of the prostate. Half of the men were treated medically with the luteinizing hormone-releasing hormone analogue leuprolide, while the other half underwent bilateral therapeutic orchiectomy. In addition, differences in hospital cost to treat these men were calculated.. During a mean followup of 24 months leuprolide treated patients were charged $500.00 per month of treatment compared to average monthly expenditure of $226.00 for orchiectomy patients during a 23-month interval. By 9 months charges incurred by both groups were equal and by 20 months medically treated patients accumulated urological charges twice that of the surgically treated patients. The true hospital cost to treat these patients followed the same trend, that is the medically treated group cost twice as much to treat by 15 months. For the average stage D2 case leuprolide therapy charges were $9,420, or 63%, more than orchiectomy. Similarly, leuprolide cost the hospital $8,924 more than surgery.. Medical management of metastatic prostate cancer is expensive. With broadening applications and androgen deprivation being initiated earlier in the course of disease, the amount spent on medical therapy will continue to escalate. For patients with a life expectancy of more than 9 months orchiectomy is the most cost-effective treatment option.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Costs and Cost Analysis; Follow-Up Studies; Humans; Leuprolide; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms

Turosteride (FCE 26073) is a new, potent, and selective 5 alpha-reductase inhibitor. We have investigated its effect on tumor growth, organ weight, and serum hormone levels in rats bearing the androgen sensitive Dunning R3327 prostatic carcinoma.. Animals with tumor diameters of 0.5-1.5 cm were treated for 9 weeks with turosteride (50 and 200 mg/kg/day, 6 days a week, orally), flutamide (25 mg/kg/day, 6 days a week, orally), and leuprolide (300 micrograms/rat, every 3 weeks, subcutaneously) or they were castrated.. Turosteride was ineffective at the dose of 50 mg/kg/day, whereas at 200 mg/kg/ day it significantly decreased tumor growth by 45%. Flutamide and leuprolide were highly effective in reducing tumor growth (70 and 77%), although their effect was slightly lower than that of castration (85%). A significant reduction of ventral prostate weight occurred in rats treated with turosteride at 50 and 200 mg/kg/day (53% and 60%). In contrast to leuprolide and castration, the inhibitory effect of turosteride on tumor growth and prostate weight was not associated to any decrease in serum testosterone.. Turosteride has antitumor activity on Dunning prostatic tumor growth and its role in prostatic cancer treatment is worthy of further investigation.

Topics: 5-alpha Reductase Inhibitors; Adenocarcinoma; Androstenedione; Animals; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Dihydrotestosterone; Enzyme Inhibitors; Finasteride; Flutamide; Leuprolide; Luteinizing Hormone; Male; Organ Size; Pituitary Gland, Anterior; Prostate; Prostatic Neoplasms; Random Allocation; Rats; Seminal Vesicles; Testis; Testosterone

Androgen deprivation therapy with analogues of luteinizing hormone-releasing hormone produces distinctive histological changes in neoplastic and nonneoplastic prostate tissue. Others have described these features in cases in which treatment status was known. To our knowledge the specificity and sensitivity of luteinizing hormone-releasing hormone effects based only on histology and possible reasons for interobserver variation have not been addressed previously.. Slides from 97 prostatectomies performed in a 3-year period were reviewed by 2 observers blinded to knowledge of previous hormonal treatment. The observers evaluated each case, recording the presence or absence of 14 features associated with androgen deprivation therapy, and then made an overall assessment regarding treatment status.. Of the 97 patients 31 had received androgen deprivation therapy with the luteinizing hormone-releasing hormone agonist leuprolide. A luteinizing hormone-releasing hormone effect was identified by the 2 observers in 26 and 28, respectively, of the 31 cases (83.9 versus 90.3% sensitivity and 92.4 versus 80.3% specificity). Including focal changes as consistent with androgen deprivation therapy increased sensitivity but decreased specificity. Of the 14 features 12 had a significant association for predicting treatment status.. Interobserver variations in interpretation occurred although both examiners were experienced in the evaluation of luteinizing hormone-releasing hormone effects and they used exactly the same criteria. These variations were apparently due to differences in the value (mental weight) given by each observer to the features assessed in each case. Predicting treatment status was optimized by noting a luteinizing hormone-releasing hormone effect only when changes were diffuse, improving specificity significantly with only a modest decrease in sensitivity.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Humans; Leuprolide; Male; Middle Aged; Observer Variation; Predictive Value of Tests; Prostatic Neoplasms; Sensitivity and Specificity

Combined androgen blockade (CAB) (medical or surgical castration plus antiandrogen therapy) is considered by many to be the optimal endocrine maneuver for patients with metastatic prostate carcinoma. When progression occurs after CAB, the discontinuation of the antiandrogen is recommended. The authors present a patient that had a clinical complete response to flutamide withdrawal plus hydrocortisone that, at last follow-up, had been maintained for more than 46 months.. A 71-year-old man with a positive family history of prostate carcinoma presented in 1989 with urinary frequency and a suspicious digital rectal examination. He was found to have a poorly differentiated adenocarcinoma (Gleason 4+4). He was started on CAB and his prostate specific antigen (PSA) concentration declined from 96 ng/mL to the normal range and was maintained for the next 24 months. In 1991 his PSA began to rise, and reached 64 ng/mL by 1993. The patient was enrolled on a clinical trial that discontinued the flutamide administration and hydrocortisone was initiated.. Physical examination at the time of enrollment was unremarkable. His PSA declined to below the limits of detection after this maneuver and at last follow-up had been maintained there for more than 46 months. In 1995, the patient underwent a repeat biopsy of the prostate and all six tissue cores were negative for carcinoma. At last follow-up in December 1996, the patient had no evidence of disease and was being followed routinely; however, the authors were continuing treatment with testicular suppression (leuprolide) plus hydrocortisone.. The authors believe the residual androgens and steroids produced by the adrenal cortex play a meaningful role in prostate carcinoma cell proliferation. Based on this case and data from trials supporting the activity of flutamide withdrawal plus adrenal suppression, it appears reasonable to evaluate prospectively the discontinuation of antiandrogen versus antiandrogen withdrawal plus adrenal suppression in individuals failing CAB.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anti-Inflammatory Agents; Antineoplastic Agents, Hormonal; Biopsy; Disease Progression; Disease-Free Survival; Flutamide; Follow-Up Studies; Humans; Hydrocortisone; Leuprolide; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction

Occult dissemination of tumor cells mainly determines the prognosis of patients with primary prostate cancer. The effect of androgen deprivation on micrometastatic tumor cells in these patients is currently unknown. We therefore used an immunocytochemical assay with monoclonal antibodies (MAbs) directed against epithelial cytoskeleton proteins (i.e., cytokeratins) to monitor the concentration of isolated tumor cells in the bone marrow of 36 prostate cancer patients (stage C), who underwent hormonal androgen deprivation with Flutamide and Leuprorelin acetate. Tumor cells in cytologic bone marrow preparations were detected using an assay that employed the MAb CK2 directed against cytokeratin (CK) 18 and the alkaline anti-alkaline phosphatase staining method. Prior to therapy, we detected between 1 and 38 CK-positive cells per sample of 2 x 10(6) nucleated cells in 21 patients, while the remaining 15 patients displayed tumor-free marrow samples. There was no significant correlation between the concentration of CK-positive cells and the volume of hypo-echogenic lesions as an indicator of the primary tumor volume or the serum level of prostate-specific antigen (PSA). After androgen deprivation, 20 of the 21 initially positive patients either became negative (n = 16) or showed at least a reduction in the concentration of CK-positive cells (n = 4). Moreover, only 2 of the 15 patients with negative pre-treatment findings became positive. All of the 7 patients with remaining tumor cells in the bone marrow after therapy showed no detectable amounts of PSA in their serum. Our findings suggest that serum PSA concentration is no indicator of micrometastatic disease in bone marrow. Neoadjuvant androgen deprivation appears to eliminate disseminated CK-positive tumor cells present in bone marrow, a preferred site of overt metastasis in prostate cancer patients.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Neoplasms; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Flutamide; Follow-Up Studies; Humans; Keratins; Leuprolide; Male; Neoplasm Proteins; Prognosis; Prostatectomy; Prostatic Neoplasms; Treatment Outcome; Ultrasonography

Apoptosis in prostate cancer was evaluated after three months of combined endocrine therapy to investigate the association with tumour grade, tumour stage, and the immunohistochemical detection of p53 and bcl-2 in tumour cells before and after therapy.. Twenty six formalin fixed, paraffin wax embedded core biopsies and corresponding prostatectomy specimens, excised after three months of combined endocrine therapy, were analysed for the presence of apoptotic cells by the terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labelling (TUNEL) method, and for p53 and bcl-2 overexpression by immunohistochemistry.. All 26 adenocarcinomas were clinically localised at diagnosis. In biopsies performed before combined endocrine therapy, the apoptotic indices varied between 0.09% and 1.73%, while the tumour grade fell between Gleason score 1 and 8. The mean (SD) apoptotic count pretherapy was 0.71% (0.50). There was a significant association between elevated apoptotic counts and higher Gleason scores in the biopsies (p = 0.005). After three months of therapy, the percentage of apoptotic tumour cells increased independently of tumour stage, while a significant association with Gleason grade was found (p = 0.0018) and all the tumours had Gleason scores of < 7. In eight cases the apoptotic index was more than twice its pretherapy value. The remaining tumours showed less of an increase in the apoptotic index (five cases) or a reduction in the percentage of apoptotic cells. The overall moderate increase in apoptotic index after combined endocrine therapy was not statistically significant (p = 0.8). Immunoreactivity to p53 was absent in all cases, before and after therapy, while a slight increase in the number of cells overexpressing bcl-2 was observed in five of the 13 tumours (38.1%) with reduced apoptotic indices after therapy.. After three months of combined endocrine treatment a minority of clinically localised prostate neoplasms showed regressive epithelial alterations, associated with an increase in apoptotic tumour cells; an increase in cells overexpressing bcl-2 was observed in five of the 13 tumours with reduced apoptotic indices.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Flutamide; Humans; Immunoenzyme Techniques; In Situ Hybridization; Leuprolide; Male; Middle Aged; Neoplasm Proteins; Prostatic Neoplasms; Proto-Oncogene Proteins c-bcl-2

An 81-year-old man on chronic hemodialysis was referred to our hospital with urinary difficulty. Transperineal needle biopsy of a hard nodule in the prostate revealed moderately differentiated adenocarcinoma. He was diagnosed to have stage C prostate cancer. A standard dose of luteinizing hormone-releasing hormone (LH-RH) analogue, leuprorelin acetate (3.75 mg), was administered every 4 weeks for 15 months. No adverse effects were observed throughout the period. The clinical response to LH-RH analogue was excellent, with normalization of serum prostate-specific antigen level and relief of dysuria. Thus the standard dosage of LH-RH analogue is considered to be adequate for hemodialysis patients.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Diabetic Nephropathies; Humans; Leuprolide; Luteinizing Hormone; Male; Prostatic Neoplasms; Renal Dialysis; Testosterone

Suramin has demonstrated modest activity against prostate cancer and is being investigated in clinical trials. We describe a patient with metastatic prostate cancer who developed nonoliguric renal failure during treatment with suramin. Other potential causes of renal failure were not present in our patient and his renal function gradually recovered with the cessation of suramin treatment. Acute renal failure should be recognized as a potential complication of suramin treatment.

Topics: Acute Kidney Injury; Adenocarcinoma; Androgen Antagonists; Anti-Inflammatory Agents; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Flutamide; Humans; Hydrocortisone; Leuprolide; Lumbar Vertebrae; Male; Middle Aged; Prostatic Neoplasms; Sacrum; Spinal Neoplasms; Suramin; Thoracic Vertebrae

Metastatic involvement of the pituitary gland is a very unusual presentation of prostatic cancer. We report a favorable response to medical treatment in such a patient.. A 77-year-old man presented with blindness, ophthalmoplegia in his left eye, and mild impairment of memory and mental status. Neuroradiological studies showed a huge intra- and suprasellar lesion that destroyed the sellar floor and extended into the sphenoid sinus. Transsphenoidal biopsy of the lesion demonstrated a prostatic adenocarcinoma. Postoperative studies revealed an enlarged prostate gland and multiple lytic bone lesions. The patient was treated with a combination of leuprolide acetate plus flutamide. Four months later, the patient exhibited a marked improvement in his neurologic status and regained vision in the right eye (visual acuity 6/20). Repeat magnetic resonance imaging of the sellar region confirmed a striking shrinkage of the prostatic metastasis. The clinical status remained stable for 22 months, after which time the disease progressed and the patient died 25 months after beginning treatment.. A favorable response to combined androgen blockade suggests that medical therapy should be considered the therapy of first choice when surgical removal of the metastatic lesion in the pituitary is impossible or too risky.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Neoplasms; Diagnosis, Differential; Flutamide; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Neoplasm Metastasis; Pituitary Neoplasms; Prostatic Neoplasms; Time Factors

Localized seminal vesicle amyloidosis is an unusual finding in surgical pathology material. Previous studies have demonstrated that the amyloid is directly produced by the seminal vesicle epithelial cells. We investigated the possible association of seminal vesicle amyloid in patients hormonally treated for prostate carcinoma.. Cases were collected from over 200 prostate needle biopsies, seminal vesicle biopsies, and prostatectomy specimens from the surgical pathology files at The Mount Sinai Hospital, New York, NY. None of the patients with seminal vesicle amyloidosis had a chronic inflammatory disorder, serum or urine protein abnormalities, or other identifiable masses.. Six cases of localized seminal vesicle amyloidosis were found in the surgical pathology material examined. Five of the six cases had prostatic carcinoma, and one case was seen in a biopsy for benign prostatic hyperplasia. Four of the five carcinoma cases had prior hormonal treatment (luteinizing hormone-releasing hormone agonist with an antiandrogen agent, and one patient, in addition, had received radiotherapy). The amyloid deposits were limited to the seminal vesicle lamina propria without involvement of vascular walls. The amyloid reacted with Congo red staining that was sensitive to potassium permanganate. Immunohistochemically, all cases were negative for AA amyloid, beta 2-microglobulin, and kappa and lambda light chains.. We raise the possibility that in some instances, prior hormonal therapy may act as a seminal vesicle epithelial stimulant for the elaboration of this protein.

Topics: Adenocarcinoma; Aged; Amyloidosis; Androgen Antagonists; Antineoplastic Agents, Hormonal; beta 2-Microglobulin; Biopsy; Drug Therapy, Combination; Epithelial Cells; Flutamide; Gonadotropin-Releasing Hormone; Humans; Immunoglobulin gamma-Chains; Immunoglobulin kappa-Chains; Immunohistochemistry; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Proteinuria; Seminal Vesicles; Serum Amyloid A Protein; Testicular Diseases

We describe a florid xanthomatous histiocytic reaction in the pelvic lymph nodes of a patient treated with androgen deprivation therapy prior to radical prostatectomy. The xanthomatous reaction was so marked that it nearly obscured the presence of metastatic carcinoma in the same lymph nodes. A similar histiocytic reaction was also present in association with carcinoma in the prostatectomy specimen, a finding that was not identified in pretreatment biopsy specimens. No other known cause of pronounced histiocytic lymph node proliferation was present in this patient. Only one brief description of a xanthomatous reaction in lymph nodes associated with this treatment has been previously recorded in the literature to our knowledge. Other patients from our institution who were treated similarly preoperatively all had lymph nodes negative for tumor, and none demonstrated a xanthomatous tissue reaction, suggesting that this reaction may be a marker for metastatic tumor in the same lymph node.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Flutamide; Histiocytes; Histiocytosis; Humans; Leuprolide; Lymph Nodes; Lymphatic Diseases; Lymphatic Metastasis; Male; Pelvis; Prostatectomy; Prostatic Neoplasms; Xanthomatosis

To determine whether there is a role for endorectal coil magnetic resonance imaging (erMRI) in the prediction of pathologic stage, margin status, and/or postoperative prostate-specific antigen (PSA) failure in patients with clinically organ-confined prostate cancer.. Using erMRI, the radiologic-pathologic correlation of extracapsular extension (ECE) and seminal vesicle invasion (SVI) was evaluated in 445 surgically managed patients. Logistic regression multivariable analysis was applied to the clinical stage, PSA, biopsy Gleason grade, and erMRI findings to assess the outcomes of ECE, SVI, positive surgical margins (PSM), and postoperative PSA failure.. The accuracy of erMRI to predict for ECE and SVI numerically decreased with both increasing PSA and biopsy Gleason score because of the increasing false-negative scans in cases of microscopic transcapsular or seminal vesicle disease. Of patients who could not be categorized into low or high risk for postoperative PSA failure on the basis of clinical stage, preoperative PSA, and biopsy Gleason score, a negative or positive erMRI for ECE or SVI stratified these patients into groups with a 78% versus 21% (P < .0001) 3-year rate of actuarial freedom from PSA failure. In this subgroup, the overall accuracy of the erMRI was 70% +/- 6% and 94% +/- 2% for ECE and SVI, respectively. The most significant predictor on multivariable analysis of PSM was the erMRI finding of ECE (P = .0001).. This initial report suggests that a preoperative erMRI can identify clinically organ-confined prostate cancer patients at high risk for having ECE, SVI, and PSM that otherwise would be missed on the basis of the clinical stage, preoperative PSA, and biopsy Gleason score. Confirmatory studies are needed.

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Biopsy; Combined Modality Therapy; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Predictive Value of Tests; Prognosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Sensitivity and Specificity

Flutamide is a nonsteroidal antiandrogen commonly used in the treatment of prostate cancer. Hepatic toxicity associated with flutamide has been reported with an incidence from less than 1% to about 5%. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been widely used in the treatment of cholesterol gallstones and of several liver diseases, but few data are now available concerning its use in the management of drug-induced hepatitis. The case of a patient who presented severe hepatitis with jaundice following use of flutamide is reported. UDCA treatment was started on admission and, contemporaneously, flutamide was withdrawn. Clinical and biochemical improvement was progressively observed, and the patient was discharged six weeks after the admission. Since fatal flutamide-related hepatitis has been reported, monitoring of serum liver tests is advocated during flutamide administration, and the effectiveness of UDCA in the treatment of drug-induced hepatotoxicity requires further study.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Chemical and Drug Induced Liver Injury; Flutamide; Humans; Leuprolide; Male; Prostatic Neoplasms; Ursodeoxycholic Acid

A spontaneous colonic adenocarcinoma and endometriosis was diagnosed in a 34-year-old female rhesus macaque (Macaca mulatta). The tumor caused partial obstruction of the ascending colon and histologically resembled the commonly described napkin-ring tumors of the descending and sigmoid colon found in humans. Serum levels of CA 125, a high-molecular-weight glycoprotein antigen that has been reported elevated in a variety of pathological conditions of the pelvic cavity in humans, was severely elevated. Both the adenocarcinoma and the endometriosis may have contributed to this finding.

Topics: Adenocarcinoma; Animals; Carcinoembryonic Antigen; Colonic Neoplasms; Endometriosis; Female; Humans; Hysterectomy; Leuprolide; Macaca mulatta; Primate Diseases

An 89-year-old man with bilateral leg edema and a huge abdominal mass was admitted for further evaluation. CT scan showed a hugh prostatic mass which occupied the whole pelvis cavity accompanying multiple pelvic bone metastases. Suprapubic needle biopsy revealed that the mass was well differentiated adenocarcinoma of prostate origin. The treatment was initiated by 500 mg per day of estramustine phosphate combined with injectable LH-RH analogue 2 months later. The serum levels of tumor markers were markedly elevated at the first visit; PSA 210ng/ml, PAP 110ng/ml, gamma-Sm 800ng/ml. They became normalized 3 months after the initiation of the treatment, and the mass was reduced to 11.5% of the initial size, which lead to removal of indwelling urethral catheter. The patient and his family, however, refused further treatment and the patient died of disseminated disease 8 months later.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Neoplasms; Estramustine; Humans; Leuprolide; Male; Prostatic Neoplasms

We report an unusual case of bilateral choroidal masses developing in a patient with metastatic prostate cancer. Visual symptoms resolved and ocular mass lesions regressed after initiating total androgen deprivation. The natural history and management of choroidal metastatis originating from prostate cancer is discussed.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Hormonal; Choroid Neoplasms; Flutamide; Humans; Leuprolide; Male; Prostatic Neoplasms

The introduction of the endorectal coil magnetic resonance imaging (MRI) technique has improved the accuracy of preoperative staging for prostate cancer. This study quantifies the improvement in the ability to identify clinically unsuspected extraprostatic disease with the use of the endorectal coil MRI.. A retrospective review of the pathologic findings of 347 patients with prostate cancer treated with a radical retropubic prostatectomy was performed. The preoperative clinical indicators including prostate specific antigen (PSA), clinical stage, Gleason score, and endorectal coil MRI data were employed in a multivariate analysis to identify patients who were at high risk for seminal vesicle invasion (SVI) or extracapsular extension (ECE). The sensitivity, specificity, and positive and negative predictive values for predicting SVI and ECE were calculated using the significant clinical indicators found on the multivariate analysis.. The clinical factors identified on multivariate analysis as significant predictors of SVI include the endorectal coil MRI data (P < 0.0001), PSA (P = 0.0096), and the Gleason score (P = 0.012). Endorectal coil MRI data (P < 0.0001), PSA (P = .0001), and Gleason score (P < .0001) were significant predictors of ECE. In the patient subgroup with PSA (> 10-20 ng/ml) and Gleason score of 5 to 7, the addition of the endorectal coil MRI data enabled an additional 71 and 27% of patients with SVI and ECE, respectively, to be correctly identified. These patients would have been missed based on the prediction obtained from the PSA and Gleason score alone.. The use of the endorectal coil magnetic resonance imaging data, in addition to prostate specific antigen and Gleason score, provides a more accurate prediction of the pathologic outcome of seminal vesicle invasion and extracapsular extension than the PSA and Gleason score alone for the patient subgroup with a PSA of greater than 10 to 20 ng/ml and Gleason score of 5 to 7.

Topics: Adenocarcinoma; Combined Modality Therapy; Forecasting; Genital Neoplasms, Male; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Staging; Predictive Value of Tests; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Rectum; Retrospective Studies; Risk Factors; Seminal Vesicles; Sensitivity and Specificity

A Cox regression multivariate analysis was done to determine the clinical and pathological indicators that predict for prostate specific antigen (PSA) failure in 347 patients who underwent radical prostatectomy for clinically localized prostate cancer between 1989 and 1993. In the patient subgroups (PSA less than 20 ng./ml. and biopsy Gleason sum 5 to 7 or PSA more than 10 to 20 ng./ml. and biopsy Gleason sum 2 to 4) not classifiable into those at high and low risk for postoperative PSA failure using PSA and biopsy Gleason sum, the status of the seminal vesicles and prostatic capsule on endo-rectal coil magnetic resonance imaging (MRI) allowed for this categorization. Specifically, 2-year actuarial PSA failure rates were 84% versus 23% in patients with and without seminal vesicle invasion, respectively, on MRI (p < 0.0001) and 58% versus 21% in those with and without extracapsular extension, respectively (p = 0.0001). In patients with extracapsular extension but without pathological involvement of the seminal vesicle(s) or poorly differentiated tumors (pathological Gleason sum 8 to 10), the 2-year actuarial PSA failure rates were 50% (margin positive), 28% (margin negative with established extracapsular disease) and 9% (margin negative with focal microscopic extracapsular disease). Therefore, endo-rectal coil MRI showing seminal vesicle invasion or extracapsular extension when the PSA level is less than 20 ng./ml. and the biopsy Gleason sum is 5 to 7 or the PSA level is more than 10 but less than 20 ng./ml. and the biopsy Gleason sum is 2 to 4 predicted for PSA failure. In patients with extracapsular extension who had pathological Gleason sum less than 8 disease with uninvolved seminal vesicles, the margin status and extent of extracapsular disease predicted for PSA failure.

Topics: Actuarial Analysis; Adenocarcinoma; Biopsy; Chemotherapy, Adjuvant; Follow-Up Studies; Forecasting; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Staging; Preoperative Care; Prognosis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Risk Factors; Seminal Vesicles; Treatment Failure

To evaluate the efficacy of combined radiation and hormonal therapy in patients with prostate cancer metastatic to the pelvic lymph nodes.. Fifty consecutive patients with node-positive prostate cancer were evaluated by the Departments of Urology and Radiation Oncology at the University of Pennsylvania and offered combined hormonal and radiation therapy. All patients received pelvic radiation to 45 Gy, with a boost dose to the prostate to 65 to 71 gy. Forty-five of the patients were treated with concurrent hormonal therapy consisting of diethylstilbestrol (2 patients), orchiectomy (18 patients), leuprolide (5 patients), or combined androgen blockade (20 patients); the other 5 patients declined hormonal therapy. Patients represented a group with locally advanced disease with a high incidence of T3 tumors (66%), high grade (74%; Gleason score more than 7), high prostate-specific antigen (PSA) (40%; more than 30.0 ng/mL), and a high incidence of gross (36%) or bilateral (30%) adenopathy and a high incidence of multiply involved lymph nodes (62%).. Median follow-up of patients is 42 months (range, 10 to 102). All 5 patients declining hormonal therapy relapsed within 18 months and only 1 patient survived longer than 3 years. Among patients treated with combined hormonal and radiation therapy, the 6-year survival rate is 82%, the clinical disease-free survival at 6 years is 71%, and the probability of survival free of recurrence, with a PSA less than 0.2 ng/mL, is 62%. Only two PSA recurrences occurred, both in patients who elected to discontinue hormone therapy. There was no synergistic toxicity observed as a result of combined therapy.. Combined hormonal and radiation therapy offers the potential for extended disease-free survival and may represent an effective treatment option for patients with locally advanced prostate cancer.

Topics: Adenocarcinoma; Aged; Combined Modality Therapy; Diethylstilbestrol; Disease-Free Survival; Flutamide; Follow-Up Studies; Humans; Leuprolide; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Orchiectomy; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage; Time Factors

We report a primary squamous cell carcinoma of the prostate that developed in a 57-year-old man, 3 years after treatment with leuprolide and flutamide for Stage D1 adenocarcinoma of the prostate. This is the first case that describes this transformation from adenocarcinoma to squamous cell carcinoma following the use of luteinizing hormone agonists.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Cell Transformation, Neoplastic; Flutamide; Humans; Leuprolide; Male; Middle Aged; Neoplasms, Second Primary; Prostatic Neoplasms

A massive, locally extensive adenocarcinoma of the prostate (2,246 ccm) presenting as constipation and a palpable abdominal mass, was treated with androgen deprivation resulting in a 94 percent reduction in tumor size, and relief of symptoms. Serum prostate-specific antigen was reduced from 4,029 to 0.4 ng/mL, after hormonal therapy was combined with radiation treatments for local disease control.

Topics: Adenocarcinoma; Aged; Combined Modality Therapy; Constipation; Flutamide; Humans; Leuprolide; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy Dosage

To determine whether hormonal therapy prior to radical prostatectomy (neoadjuvant hormonal therapy) leads to improved results in patients with stage C prostate cancer.. Thirty patients received neoadjuvant hormonal therapy for stage C carcinoma of the prostate. Eighteen patients who responded to treatment subsequently underwent extirpative surgery.. Fourteen of the 30 patients (47%) were diagnosed as being downstaged to clinical stage B disease following therapy. No major complications occurred. Pathology staging revealed only three patients (10%) to have organ-confined disease after radical prostatectomy.. Neoadjuvant hormonal therapy prior to radical prostatectomy offers little probability of rendering patients with clinical stage C carcinoma of the prostate free of disease. Further investigation of the efficacy of this treatment should be accomplished in randomized trials.

Topics: Adenocarcinoma; Aged; Chemotherapy, Adjuvant; Diethylstilbestrol; Flutamide; Humans; Leuprolide; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms

Metastases to the meninges from prostatic cancer are rare, accounting for less than 0.5% of all solid tumor cases. Management for patients with leptomeningeal metastases of various histologic types includes intrathecal chemotherapy and radiation therapy, but the prognosis is poor. Therefore, the identification of selected patients for whom effective therapy exists is of paramount importance.. A patient with adenocarcinoma of the prostate presented with leptomeningeal metastases as his first manifestation of metastatic disease.. Androgen blockade was initiated with flutamide and ketoconazole. After 5 days of therapy, leuprolide acetate depot was substituted for ketoconazole. The patient responded to therapy and remained asymptomatic with a normal serum prostate-specific antigen levels at 16-plus months with no further evidence of malignant cells in spinal fluid from repeated lumbar punctures.. Patients with hormone-naive metastatic prostatic carcinoma manifested as carcinomatous meningitis should be considered for hormonal ablative therapy. This is preferred to the use of intrathecal chemotherapy, which has limited efficacy.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Flutamide; Follow-Up Studies; Humans; Ketoconazole; Leuprolide; Male; Meningeal Neoplasms; Meningitis; Prostatic Neoplasms

A 73-year-old man presented with dyspnea, right-sided pleural effusion, and bilateral pulmonary infiltrates. The pleural fluid revealed adenocarcinoma cells that stained positively for prostatic specific antigen (PSA), which confirmed this uncommon metastatic involvement from prostate cancer. The dyspnea, effusion, and infiltrates disappeared after therapy with flutamide and leuprolide was started. This report demonstrates both the usefulness of immunocytochemical staining for PSA in ascertaining the origin of malignant pleural effusion in men and the effectiveness of the aforementioned endocrine therapy in such setting.

Topics: Adenocarcinoma; Aged; Flutamide; Humans; Leuprolide; Male; Pleural Effusion, Malignant; Pleural Neoplasms; Prostatic Neoplasms

A case of prostatic cancer treated with an LH-RH analogue depo-preparation was found to have a mediastinal thymoma which was later removed by surgery. The association of thymoma and prostatic cancer has not been documented in the world literature, and it remains to be elucidated whether the occurrence of the both tumors is a coincidence or etiologically inter-related.

Topics: Adenocarcinoma; Aged; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Neoplasms, Multiple Primary; Prostatic Neoplasms; Remission Induction; Thymoma; Thymus Neoplasms

Six patients with advanced prostatic cancer who had been treated by long-term administration of LH-RH agonistic preparations (Buserelin or Leupron) were tested for their pituitary-testicular endocrine functions. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), prolactin (PRL), estradiol (E2) and dihydrotestosterone (DHT) were measured consecutively. In all medically castrated patients, serum levels of LH, FSH, T, DHT and E2 were suppressed and particularly serum T levels were below the castration level of 1.0 ng/ml. On the other hand, serum PRL levels were unchanged after the long-term treatment with the agonists. Serum LH and FSH levels failed to respond to LH-RH stimulation after the treatment, whereas serum T responded to stimulation by human chorionic gonadotropin (hCG) to various degrees. It was remarkable that, in 4 out of 6 medically castrated patients treated up to more than 3 years, serum T response levels above 1.0 ng/ml were noted. It is suggested that testicular endocrine function to secrete T and DHT in patients under treatment with long-term LH-RH agonist administration are still preserved in response to hCG stimulation.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Buserelin; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Testis; Testosterone

A luteinizing hormone-releasing hormone (LH-RH) analogue was administered for 3 to 32 months to 15 prostatic cancer patients in stage B-D (B:3, C:8, D:4). Intratesticular, intratubular and prostatic androgen levels were measured by radioimmunoassay before and after LH-RH analogue therapy. The measurement of serum prostatic acid phosphatase (PAP) and prostatic specific antigen (PA) levels was also conducted. Thereafter, we assessed the effect of the LH-RH analogue on androgen levels and the relation of prostatic tissue 5 alpha-dihydrotestosterone (DHT) level to the clinical response. The results were as follows: 1) Johnsen's mean germinal epithelium count was significantly decreased from 7.7 +/- 2.1 (mean +/- S.D.) to 4.3 +/- 2.3, and the wall thickness of seminiferous tubules was increased from 5.93 +/- 1.31 to 11.9 +/- 3.64 microns. 2) Plasma testosterone (T), intratesticular and intratubular androgen levels were significantly decreased (plasma T: from 4.40 +/- 1.84 to 0.61 +/- 0.32 ng/ml, intratesticular T: from 335.3 +/- 170.3 to 4.6 +/- 3.8 ng/g.t.w., DHT: from 25.3 +/- 11.7 to 3.7 +/- 2.7 ng/g.t.w., intratubular T: from 50.8 +/- 36.6 to 0.10 +/- 0.99 ng/g.t.w. and DHT: 7.54 +/- 3.20 to 0.63 +/- 0.90 ng/g.t.w.). 3) Crude nuclear DHT levels in prostatic tissue fell from 15.3 +/- 9.3 (N = 8) to 0.37 +/- 0.54 pg/mg protein (N = 3) and the level was non-detectable in 5 of 8 cases. 4) Complete remission was achieved in 1 patient, partial response in 5, objective stable in 8, and objective progression in 1 patient, according to Shimazaki's criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgens; Antineoplastic Agents; Buserelin; Dihydrotestosterone; Drug Evaluation; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Remission Induction; Testosterone

The R-3327 prostatic tumor implanted in the male Copenhagen x Fischer F1 rat continues to grow because androgen is being supplied from an endogenous source. It follows that regimens which decrease the availability of androgen will retard the growth rate of the tumor. These experiments showed that castration, the antiandrogen flutamide, and the luteinizing hormone-releasing hormone (LHRH) agonist leuprolide inhibited tumor growth. Adrenalectomy alone had no significant effect on tumor size and did not further retard the growth of the tumor in castrated rats. Further, under the conditions of this study, there was no significant difference in tumor growth rates between the groups of rats treated with either flutamide alone or flutamide combined with leuprolide. Total ablation of androgen may not be needed for maximal inhibition of tumor growth.

Topics: Adenocarcinoma; Adrenalectomy; Anilides; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Evaluation, Preclinical; Flutamide; Gonadotropin-Releasing Hormone; Leuprolide; Male; Neoplasm Transplantation; Orchiectomy; Prostatic Neoplasms; Rats; Rats, Inbred F344; Time Factors

Twenty-two patients with prostatic cancer were treated for 12 to 52 weeks with the luteinizing hormone-releasing hormone agonist, (D-Leu6)-des Gly-NH2 10-LHRH ethylamide (leuprolide). The clinical efficacy of leuprolide was evaluated at 12 weeks according to NPCP criteria. All seven patients with Stage B and C disease demonstrated a partial objective regression. The objective response rate in 12 previously untreated Stage D patients was 92% (partial regression: 5; stable disease: 6). In three relapsing Stage D patients, one demonstrated stable disease and two failed to respond to leuprolide therapy. Even though the dose of leuprolide used in this study was high, no serious side effects were observed in any patients. There was a large increase in serum FSH and LH levels during the first few days of treatment, but serum FSH and LH levels fell below the initial levels by 1 and 2 weeks, respectively. Serum testosterone fell to less than 1 ng/ml within 3 weeks, and at 12 weeks it was 7.99% of the initial level. The present study shows that chronic administration of leuprolide in high doses can safely and effectively reduce the level of serum testosterone in patients with prostatic cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Biopsy; Bone Neoplasms; Carcinoma; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Prostatic Neoplasms; Testosterone; Time Factors

Leuprolide (Lupron, TAP Pharmaceuticals), a potent agonist analogue of GnRH, has been shown to suppress testicular androgen production in animals. In order to determine the potential of leuprolide as an alternative to surgical castration in human males with prostatic cancer, this agent was administered to castrate and noncastrate males with carcinoma of the prostate. Baseline and treatment levels of LH, FSH, testosterone and dihydrotestosterone were determined serially. Leuprolide suppressed pituitary production of LH and FSH and, consequently, testicular production of testosterone and dihydrotestosterone. This agent simulates the results achieved with surgical castration.

Topics: Adenocarcinoma; Antineoplastic Agents; Castration; Dihydrotestosterone; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Luteinizing Hormone; Male; Prostatic Neoplasms; Testis; Testosterone

Current management techniques for metastatic prostatic cancer have given rise to controversies regarding the optimal timing, form, and degree of androgen deprivation. Low-dose diethylstilbestrol (DES) or orchiectomy decrease serum testosterone levels while posing less cardiovascular risk than high-dose DES. LH-RH analogues, such as leuprolide or buserelin, also inhibit testosterone production. Some studies suggest that some tumor cells may be relatively, rather than absolutely, androgen dependent. This has been the rationale for the combined use of a pure antiandrogen and an LH-RH agonist. Unfortunately, while this combination has been found effective in previously untreated patients, it has not been equally effective in those who have undergone prior therapy and demonstrated disease progression.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Castration; Cyclophosphamide; Diethylstilbestrol; Estramustine; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Male; Neoplasm Metastasis; Prostatic Neoplasms

Luteinizing hormone releasing hormone (LHRH) analogs have been shown to be an effective alternative endocrine treatment of metastatic prostatic carcinoma. After a transient stimulation of testosterone (T) and dihydrotestosterone (DHT) during the first week of therapy, continued administration of LHRH analogs has reliably suppressed serum androgens to castrate levels. About 10 per cent of previously untreated patients begun on LHRH therapy will experience transient worsening of disease symptoms corresponding to the initial rise in androgen levels. In an attempt to eliminate the early rise of T and DHT, 9 patients with metastatic prostatic carcinoma were pretreated with diethylstilbestrol (DES), 3 mg/day, for one week prior to the initiation of LHRH therapy. Following this, both DES and LHRH were given concomitantly for a week, after which DES was discontinued. LHRH was then continued as long as patients experienced clinical benefit. T and DHT levels were performed pre-study and on days 4, 8-11, 13, 15, and 29 of study. Results indicate that pretreatment with DES did not completely prevent the rise in T and DHT seen during the first week of LHRH therapy, although T and DHT levels rose to only slightly above baseline during the first four days. T and DHT levels then markedly decreased, and castrate levels were achieved by day 29 of treatment.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Diethylstilbestrol; Drug Administration Schedule; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Male; Prostatic Neoplasms; Testosterone; Time Factors

Ketoconazole is a potent inhibitor of the P450 series of enzymes that are essential for the production of androgens. In order to determine the effects of ketoconazole on androgen production and androgen dependent tissues in the rat, adult male rats were administered varying doses of ketoconazole every 12 hours. Serum testosterone declined to unmeasurable levels at ketoconazole doses of greater than 4 mg. This dose was sufficient to completely inhibit the testosterone surge induced by the administration of a potent luteinizing releasing hormone agonist. The ventral prostate weight of normal rats and the volume of the Dunning R3327H androgen dependent prostatic cancer declined at the same rate in animals treated with ketoconazole or castration. Ketoconazole may be an effective agent to treat androgen dependent diseases.

Topics: Adenocarcinoma; Animals; Castration; Depression, Chemical; Gonadotropin-Releasing Hormone; Half-Life; Ketoconazole; Leuprolide; Male; Neoplasms, Hormone-Dependent; Organ Size; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testosterone

At least 80 per cent of prostatic tumors exhibit some degree of hormone responsiveness. The preferred method of hormonal alteration has yet to be determined because new agents are currently undergoing clinical trials. The compounds tested have included cyproterone acetate, a progestational agent; flutamide, an antiandrogen that blocks the DHT-receptor complex in the tumor cell; and aminoglutethimide, which inhibits adrenal steroid production and, therefore, might further lower the level of circulating androgen following bilateral orchiectomy. The introduction of potent, synthetic analogues of gonadotropin-releasing hormone (GnRH) has provided another method of reducing the level of circulating androgen. A recent report on the efficacy of one of these analogues--leuprolide--in men with newly diagnosed metastatic prostatic cancer has revealed an initial response rate of 76 per cent (4% complete remissions, 32% partial remissions, and 40% stable) using National Prostatic Cancer Project criteria.

Topics: Adenocarcinoma; Aminoglutethimide; Androgen Antagonists; Bone Neoplasms; Buserelin; Flutamide; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Megestrol; Megestrol Acetate; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms