leuprolide and Carcinoma

Topics: Age Factors; Carcinoma; Clinical Trials as Topic; Disease Models, Animal; Female; Follicle Stimulating Hormone; Gonadotropins; Goserelin; Humans; Leuprolide; Luteinizing Hormone; Menopause; Middle Aged; Ovarian Neoplasms; Receptors, LHRH; Remission Induction; Risk Factors; Survival Rate; Treatment Outcome; Triptorelin Pamoate

Metastatic prostatic cancer can be present in a variety of different ways. The authors describe the differences among stages D-0, D-1, and D-2 disease and present the treatment options for each of the substages. They summarize and integrate the clinical evidence that bears on the potential efficacy of each treatment.

Topics: Acid Phosphatase; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma; Castration; Clinical Trials as Topic; Combined Modality Therapy; Diethylstilbestrol; Estrogens; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms; Radioisotope Teletherapy

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

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

The investigational objectives of this open, noncomparative phase I study were to determine the pharmacokinetic profile of a single dose of 11.25 mg leuprorelin acetate, the effective duration of the chemical castration (serum testosterone < or = 1.73 nmol/l) and safety in patients with locally advanced and/or metastatic carcinoma of the prostate foreseen for chemical castration, in the hope that such a dose of leuprorelin acetate may be suitable as a depot formulation to be administered 3-monthly to these patients.. A total of 24 males up to 85 years old with histologically proven advanced carcinoma of the prostate were enrolled in the study to obtain 18 eligible patients. Each patient was given 11.25 mg of leuprorelin acetate in a depot formulation subcutaneously after reconstitution in 2 ml of a special suspension vehicle. The study period lasted 24 weeks. Patients whose serum testosterone levels reincreased prior to the end of the observation period of 24 weeks were withdrawn from the study and received the monthly depot formulation of 3.75 mg of leuprorelin acetate.. The 3M-depot formulation of leuprorelin acetate ensured continuous and constant drug release and effective suppression of testosterone serum levels to castration range for at least 13 weeks. After an initial rise, 5 alpha-dihydrotestosterone as well as the gonadotropin serum levels of luteinizing hormone and follicular stimulating hormone reflected the testosterone serum pattern.. The results of this study show that the 3M-depot preparation of leuprorelin acetate is effective in suppressing the serum testosterone levels to the castration range for a targeted period of at least 13 weeks.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Carcinoma; Delayed-Action Preparations; Dihydrotestosterone; Evaluation Studies as Topic; Follicle Stimulating Hormone; Humans; Injections, Subcutaneous; Leuprolide; Linear Models; Luteinizing Hormone; Male; Middle Aged; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatic Neoplasms; Severity of Illness Index; Statistics, Nonparametric; Testosterone; Treatment Outcome

To determine median survival time, median time to tumor progression and maintenance of testosterone suppression (i.e. < or = 50 ng/dl) during long-term treatment with subcutaneous injections of leuprorelin acetate 3-month depot (LAD-3M). In Germany 62 patients with advanced prostate cancer participated in a prospective, randomized, multicenter phase II trial as part of a European study. Of these, 37 patients entered the follow-up study.. Standard clinical investigations and methods were employed in the study.. Twenty-five of the 62 (40.3%) patients died during the course of the study. No death had a causal relationship with the study drug. Median survival time, median time to tumor progression and median period of progression-free survival were 1,149 (3.1 years), 1,015 (2.8 years) and 680 days (1.9 years), respectively. Adequate suppression of testosterone serum levels to the castration range was confirmed. Objective and subjective response as well as the safety profile were comparable to previously published results with LAD-3M, LAD-1 M and other LHRH analogues.. The results of this follow-up study confirm long-term efficacy and safety of LAD-3M for treatment in advanced prostate cancer. LAD-3M is a suitable alternative to the established shorter-acting LHRH-a depot formulations.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Neoplasms; Carcinoma; Delayed-Action Preparations; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Europe; Follow-Up Studies; Germany; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Testosterone; Time Factors

Leuprolide acetate (Lupron, TAP Pharmaceuticals, North Chicago), a gonadotropin-releasing hormone analogue, was administered subcutaneously at a 1-mg dose for a minimum of 8 weeks to 23 patients with refractory epithelial ovarian cancer. Eighteen of these patients were evaluable. There were no complete responses. Four patients (17%) had a partial response, with a median duration of 52 weeks. Three of six patients with grade 1 carcinomas had a partial response and two had stabilized disease. There was only one response among 15 patients with grade 2 or 3 disease. Therapy was well tolerated, with three patients complaining of hot flashes and two of mild pedal edema. Leuprolide acetate thus shows evidence of antitumor activity against refractory grade 1 epithelial adenocarcinoma of the ovary. Further trials with larger numbers of patients should be conducted.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma; Clinical Trials as Topic; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Middle Aged; Ovarian Neoplasms

Luteinizing hormone releasing hormone agonists presently are being evaluated in the treatment of patients with metastatic prostatic cancer. To determine the comparative benefits of a specific luteinizing hormone releasing hormone agonist [6-leu (1-9) luteinizing hormone releasing hormone nonapeptide ethylamide] relative to conventional estrogen therapy 23 patients with stage D2 prostatic cancer were randomized to receive either 1 mg. luteinizing hormone releasing hormone agonist daily (12) or 3 mg. diethylstilbestrol per day (11). Both agents were effective in inducing a remission in all patients, although diethylstilbestrol was slightly faster. The early phase of treatment with the luteinizing hormone releasing hormone agonist was dominated by a transient reversible deterioration (the flare) of the patient, which was believed to be related to the agonist-induced increase in serum androgens. At 1 year of followup adverse effects in both groups have been minor but the proportion of patients with progression in the luteinizing hormone releasing hormone agonist group (6 of 12) was significantly higher than that in the diethylstilbestrol group (0 of 11). Further investigation is required to determine the role of luteinizing hormone releasing hormone agonist in the treatment of patients with advanced prostatic cancer.

Topics: Aged; Antineoplastic Agents; Carcinoma; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Prostatic Neoplasms

Metastatic prostatic cancer can be present in a variety of different ways. The authors describe the differences among stages D-0, D-1, and D-2 disease and present the treatment options for each of the substages. They summarize and integrate the clinical evidence that bears on the potential efficacy of each treatment.

Topics: Acid Phosphatase; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Brachytherapy; Carcinoma; Castration; Clinical Trials as Topic; Combined Modality Therapy; Diethylstilbestrol; Estrogens; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Lymph Node Excision; Lymphatic Metastasis; Male; Neoplasm Staging; Prostatectomy; Prostatic Neoplasms; Radioisotope Teletherapy

BACKGROUND Salivary duct carcinoma (SDC) is a rare, aggressive head and neck cancer with frequent metastases. Current treatment options for recurrent or metastatic SDC include targeted anti-androgen therapy, HER2-targeted therapy, or systemic chemotherapy. We report the first use of a combination chemohormonal strategy. CASE REPORT A 68-year-old male who had never smoked with a past medical history of two-vessel coronary artery disease and systolic heart failure presented with a parotid mass and underwent surgical resection. Biopsy of the mass revealed high-grade, androgen receptor-positive and Erb-B2 receptor tyrosine kinase-2 (ERBB2)-amplified positive SDC. He subsequently received adjuvant radiation therapy. Four months after completion of adjuvant radiation therapy, recurrence with symptomatic pleural effusion and nodes, hepatic metastases, and boney metastases occurred. Due to significant symptomatic tumor, a rapid treatment response was desired. Combination chemohormonal therapy (CHT) was initiated with carboplatin area under the curve 4 and paclitaxel, 200 mg/m² in 21-day cycles along with combined androgen blockade using leuprolide, 45 mg subcutaneously every 6 months and bicalutamide, 50 mg daily. The treatment was well tolerated with fatigue as the main adverse event. Positron emission tomography-computed tomography at 3 and 6 months after treatment initiation showed good partial response. The patient experienced uveal progression after 8 months and alternate treatment was started. CONCLUSIONS Combination CHT with carboplatin, paclitaxel, and combined androgen deprivation may be a good treatment option in androgen receptor-positive recurrent or metastatic SDC if rapid treatment response is desired. Combination chemotherapy with androgen deprivation for validation through clinical trials.

Topics: Aged; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma; Humans; Leuprolide; Male; Nitriles; Paclitaxel; Salivary Ducts; Salivary Gland Neoplasms; Tosyl Compounds

Topics: Androgen Antagonists; Anilides; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Clinical Trials, Phase II as Topic; Disease-Free Survival; Humans; Leuprolide; Nitriles; Receptors, Androgen; Salivary Gland Neoplasms; Signal Transduction; Tosyl Compounds; Treatment Outcome

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

Residual cancer morphology in radical prostatectomies (RPs) after neoadjuvant hormone therapy includes inconspicuous cytology, and treated tumour cells can be difficult to identify in lymph nodes. The aim of this study was to evaluate the role of immunohistochemistry (IHC) in identifying occult lymph node metastases following neoadjuvant hormone treatment of prostate cancer.. One hundred and twenty-eight lymph nodes from 24 patients treated with neoadjuvant hormone therapy, including abiraterone acetate alone or combined with leuprolide, were stained with antibodies against keratin AE1/AE3, prostate-specific antigen (PSA), prostate-specific acid phosphatase (PrAP), androgen receptor (AR), and NKX3.1. IHC slides were scored 'blind', and then retrospectively compared with haematoxylin and eosin (H&E)-stained slides and pathology reports. IHC identified carcinoma in six lymph nodes from three patients. All metastases were positive for NKX3.1 and AR, five of six were positive for AE1/AE3, and three of six were positive for PSA; PrAP was negative in all metastatic foci. All six lymph node metastases had been identified by H&E staining at the time of RP.. These findings suggest that routine use of IHC on lymph nodes from neoadjuvant-treated prostate carcinomas is not necessary. Nevertheless, for suspicious small foci of atypical cells in neoadjuvant-treated lymph nodes, NKX3.1 and AR appear to have the greatest sensitivity.

Topics: Abiraterone Acetate; Aged; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma; Follow-Up Studies; Humans; Immunohistochemistry; Leuprolide; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Pelvis; Prostate; Prostatectomy; Prostatic Neoplasms; Retrospective Studies

Pituitary apoplexy is a rare complication of the initial administration of leuprolide acetate.. We present the case of a 63-year-old man who experienced headache, blurred vision, and loss of consciousness after initial leuprolide treatment for prostate carcinoma. Neuroimaging showed pituitary hemorrhage.. Clinicians should be aware of this rare but known complication of leuprolide injection so that prompt diagnosis and treatment initiation are performed in patients with leuprolide-associated pituitary apoplexy.

Topics: Antineoplastic Agents, Hormonal; Carcinoma; Cerebral Hemorrhage; Chemotherapy, Adjuvant; Humans; Leuprolide; Magnetic Resonance Imaging; Male; Middle Aged; Pituitary Apoplexy; Prostatectomy; Prostatic Neoplasms

Gonadotropin‑releasing hormone (GnRH), or its analogues have been demonstrated to exhibit anti‑proliferative effects on tumour cells in ovarian, endometrial and breast cancer through GnRH‑receptors (GnRH‑R). However, the role of GnRH in nasopharyngeal carcinoma (NPC) remains to be elucidated. In order to investigate the effects of GnRH in NPC, the present study examined the expression of the GnRH‑R transcript in NPC and investigated the phenotypic changes in HK1 cells, a recurrent NPC‑derived cell line, upon receiving GnRH treatment. Firstly, the GnRH‑R transcript was demonstrated in the NPC cell lines and four snap frozen biopsies using reverse transcription‑quantitative polymerase chain reaction. In addition, immunohistochemistry revealed the expression of GnRH‑R in two of the eight (25%) NPC specimens. Treatment with GnRH induced a rapid increase in intracellular ionised calcium concentration in the NPC cells. GnRH and its agonists, triptorelin and leuprolide, exerted anti‑proliferative effects on the NPC cells, as determined using an MTS assay. GnRH did not induce any cell cycle arrest in the HK1 cells under the conditions assessed in the present study. Time‑lapse imaging demonstrated a reduction in cell motility in the GnRH‑treated cells. In conclusion, GnRH, or its analogues may have antitumour effects on NPC cells. The consequences of alterations in the levels of GnRH on the progression of NPC require further examination.

Topics: Antineoplastic Agents, Hormonal; Carcinoma; Cell Line, Tumor; Cell Movement; Cell Proliferation; Gonadotropin-Releasing Hormone; Humans; Immunohistochemistry; Leuprolide; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Receptors, LHRH; Triptorelin Pamoate

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

Leuprorelin acetate is an agonist of gonadotropin-releasing hormone, used as a first choice treatment in patients with prostate carcinoma. The impact of leuprorelin therapy in liver function and metabolism is largely unknown. We report about a patient who had been treated for 32 months with leuprorelin acetate, who developed a nonalcoholic fatty liver disease (NAFLD), associated with a focal lesion at the IV hepatic segment where histologic features appeared to be more severe. The patient, in addition to NAFLD, presented a marked iatrogenic hypotestosteronemia and full-criteria meeting the diagnosis of metabolic syndrome, including insulin resistance. The radiologic and clinical findings, the histopathologic features, and the absence of any hepatic abnormalities before treatment, support a causal role of leuprorelin in inducing metabolic derangement that, most likely secondary to androgen-deprivation, were, in turn, responsible for the development of NAFLD. In conclusion, this is the first case report of NAFLD with focal fatty liver associated with leuprorelin therapy. Patients in leuprorelin should be carefully monitored for the development of liver disease.

Topics: Aged; Antineoplastic Agents, Hormonal; Carcinoma; Fatty Liver; Humans; Hypogonadism; Insulin Resistance; Leuprolide; Liver; Male; Prostatic Neoplasms; Testosterone

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma; Fatal Outcome; Flutamide; Humans; Leuprolide; Liver Neoplasms; Male; Prostatic Neoplasms; Tumor Lysis Syndrome

Topics: Antineoplastic Agents, Hormonal; Carcinoma; Drug Resistance, Neoplasm; Humans; Leuprolide; Male; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Failure

The use of complementary/alternative medicine (CAM) has recently received considerable attention throughout the world. We evaluated the prevalence and predictors of CAM use among Japanese patients with localized prostate cancer.. A total of 177 patients with localized prostate carcinoma underwent radical retropubic prostatecotomy or external beam radiation therapy between January 1994 and January 2001. Of them, 138 (78%) answered a self-administered questionnaire on CAM use and were eligible for this study. The overall prevalence, types of CAM used, and costs of CAM were assessed. The effects of age, prostate-specific antigen (PSA) level, clinical stage, pretreatment Gleason score, patients' income, patients' final educational status, and general health-related quality of life at baseline and 1 year after treatment, as estimated using the European Organization for Research and Treatment of Cancer Prostate Cancer Quality of Life Questionnaire on the prevalence of CAM use, were evaluated.. Twenty-seven patients (20%) had once used or had been using some types of CAM. Herbal medicine and vitamins were the most common types of CAM used. Preoperative Gleason score was significantly associated with CAM use, as determined by the chi(2) test ( P = 0.0198), and PSA level and posttreatment physical function domain were marginally associated with CAM use, as determined by the Mann-Whitney U-test ( P = 0.0734 and P = 0.0597, respectively). Patient age, income, and final educational status had no impact on CAM use.. A relatively small proportion of Japanese patients with localized prostate cancer have tried CAM compared with the proportions of patients described in previous reports from Western countries.

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Carcinoma; Complementary Therapies; Cross-Sectional Studies; Follow-Up Studies; Hormone Replacement Therapy; Humans; Japan; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Predictive Value of Tests; Prevalence; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiotherapy, Computer-Assisted; Surveys and Questionnaires; Treatment Outcome

Serum concentrations of luteinizing hormone (LH), testosterone, prostatic acid phosphatase (PAP) and prostatic specific antigen (PSA) were measured in 16 patients with advanced prostatic cancer before and after treatment with luteinizing hormone-releasing hormone (LHRH) analogue. An initial rise of serum LH and testosterone levels was observed on day 2 of the treatment. Subsequently, serum concentrations of PAP and PSA showed a transient increase on day 5 of the treatment. This indicates that LHRH analogues had better be given in combination with antiandrogens in patients with metastatic carcinoma of the prostate.

Topics: Acid Phosphatase; Aged; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Neoplasms; Carcinoma; Follow-Up Studies; Humans; Immunoenzyme Techniques; Injections, Subcutaneous; Leuprolide; Luteinizing Hormone; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Radioimmunoassay; Testosterone; Treatment Outcome

There has been a resurgence of interest in cryosurgical ablation of the prostate for the treatment of carcinoma. This is due to recent advances in cryosurgical technology, which have resulted in relatively lower morbidity. The objective of this study was to evaluate the effectiveness of ultrasound-guided cryosurgical ablation of prostate carcinoma.. Eighty-three patients who had biopsy-proven prostate carcinoma underwent cryosurgical ablation of their entire prostate gland. The initial group of 12 patients had their procedures performed under ultrasound guidance only. The other 71 patients had cryosurgery performed with temperature monitoring in combination with ultrasound guidance. Twelve patients who had positive biopsies underwent a second cryosurgical procedure. All patients had prostate specific antigen (PSA) levels measured at 3, 6, 12, 18, 24, and 30 months after cryosurgery. Ultrasound-guided sextant biopsies were performed at 3-6, 12-18, and 24 months.. The median PSA dropped by 95%, from a preoperative value of 4.3 ng/mL to 0.2 ng/mL 30 months after cryosurgery. The authors experienced a high failure rate (positive biopsies) of 83% for the initial group of 12 patients who did not have temperature monitoring during the cryosurgical procedure. This was in contrast to a success rate of 90% (negative biopsies) for the next 71 patients, who did have temperature monitoring (P < 0.05, chi-square test). Twelve patients underwent a second cryosurgery, and the success rate for this group was 91% (11 of 12 patients). The combined success rate for both the first cryosurgery and the second was 94% (62 of 77 patients). Complications included urethral sloughing, urinary incontinence, impotence, bladder neck contracture, and bladder contracture. The majority of patients recovered rapidly from their cryosurgical procedures and were able to resume normal activities 3-4 weeks afterward.. These preliminary results demonstrate that cryosurgical ablation of the prostate is a viable treatment option for prostate carcinoma. In the authors' experience, ultrasound alone may not be adequate for monitoring the entire cryosurgical procedure. The authors found that temperature monitoring shortened their learning curve, enabled them to freeze prostate tissue more aggressively, and may have contributed to their overall success.

Topics: Aged; Carcinoma; Cryosurgery; Erectile Dysfunction; Humans; Leuprolide; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Thermometers; Urethral Diseases; Urinary Bladder Diseases; Urinary Incontinence

It has been reported that blocking of testosterone production inhibits bladder carcinogenesis in various animal models. We investigated how testosterone acts on rat bladder carcinogenesis using an antiandrogen, flutamide, and a 5 alpha-reductase inhibitor, finasteride.. Experiment 1: we administered 0.05% BBN [N-butyl-N-(4-hydroxybutyl)nitrosamine] orally to 117 Wistar rats for 10 weeks, divided them into seven groups-control, surgical castration, finasteride (2 mg/kg), luteinizing hormone releasing hormone (LH-RH) agonist (1 mg/kg) flutamide (50 mg/kg), LH-RH agonist plus finasteride, and LH-RH agonist plus flutamide-, and then cystectomized them to investigate the incidence of bladder cancer on week 21; experiment 2: we administered 0.05% BBN to 154 Wistar rats for 7 weeks, divided them into seven groups-control, finasteride 2, 4, and 8 mg/kg, and flutamide 50, 100, and 200 mg/kg-, and then we cystectomized them to investigate the dose-dependent influence on bladder carcinogenesis of these drugs on week 20, and experiment 3: we investigated the presence of androgen receptors in rat and mouse normal bladder mucosa using a monoclonal antibody.. Experiment 1: Surgical castration and LH-RH agonist treatment significantly reduced the occurrence of carcinomas. There was no significant additive effect of coadministered finasteride or flutamide with LH-RH agonist. Finasteride or flutamide monotherapy showed no statistically significant effects on the results of experiment 1 at the doses used. Experiment 2: Flutamide showed a dose-dependent effect on reducing the number of rats with bladder cancer, and at a dosis of 200 mg/kg twice a week, the difference was statistically significant when compared with the control group, whereas finasteride had no statistically significant suppressing effect at any dose. Experiment 3: Mouse and rat bladder urothelium expressed the androgen receptor. Our results indicate that testosterone itself might have a more potent action on bladder carcinogenesis rather than its converting form, 5 alpha-dihydrotestosterone.

Topics: Administration, Oral; Androgen Antagonists; Animals; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Butylhydroxybutylnitrosamine; Carcinogens; Carcinoma; Cholestenone 5 alpha-Reductase; Disease Models, Animal; Enzyme Inhibitors; Finasteride; Flutamide; Gonadotropin-Releasing Hormone; Immunohistochemistry; Leuprolide; Male; Mice; Mice, Inbred C3H; Oxidoreductases; Rats; Rats, Wistar; Urinary Bladder Neoplasms

The use of suramin, a polysulfonated naphthylurea, in the treatment of advanced prostate cancer currently is being investigated. A 52-year-old man developed acute renal dysfunction after receiving nine doses of suramin. His suramin therapy was discontinued, but his serum creatinine level continued to rise to 10.8 mg/dl during the next 6 days. The patient was not rechallenged with suramin, and his renal function returned to baseline within the next 3 weeks. Future investigators of this drug should be aware of the possibility of such a reaction with parenteral administration.

Topics: Acute Kidney Injury; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Combined Modality Therapy; Creatinine; Flutamide; Humans; Hydrocortisone; Kidney; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Suramin

We have previously documented the responsiveness of a cell line of human ovarian epithelial carcinoma (Bowman Gray 1) heterotransplanted in nude mice to treatment with the GnRH agonist Lupron-SR. In this study we used another human ovarian epithelial carcinoma cell line, OVCAR-3, and the human endometrial carcinoma cell line HEC-1A. After a latent period, OVCAR-3 tumors showed significant inhibition of growth on Days 17, 21, and 24 (P < 0.03) compared to controls. The effect was transient and did not persist beyond Day 24. HEC-1A tumors showed no inhibition of growth. Radioreceptor assay studies utilizing native radiolabeled GnRH and [D-Lys6]-GnRH revealed no specific GnRH receptors in any of the tumor samples (BG-1, OVCAR-3, HEC-1A, University of Nebraska cell line, and two fresh human ovarian epithelial tumor samples) compared to male rat anterior pituitary cells. Binding studies and the latency and transience of effect would suggest that the mechanism of action in this animal model may be indirect. This activity may be via altered circulating steroids, gonadotropins, cell-cycle regulatory events, or some other as-yet-undefined action related to GnRH agonist administration or indirectly via effects of the metabolic products of degraded GnRH agonist such as D-amino acids, which are incorporated into the cells by constitutive or adsorptive pinocytosis. This study confirms latency and transience of effect of GnRH agonist therapy on an in vivo model of ovarian cancer.

Topics: Animals; Carcinoma; Disease Models, Animal; Endometrial Neoplasms; Female; Humans; Leuprolide; Male; Mice; Mice, Nude; Neoplasm Transplantation; Ovarian Neoplasms; Pituitary Gland, Anterior; Radioligand Assay; Random Allocation; Receptors, LHRH; Tumor Cells, Cultured

Some patients with recurrent ovarian epithelial cancer respond favorably to treatment with GnRH agonists. This effect was proposed to be mediated by suppression of pituitary gonadotropin release. The present in vitro study investigated effects of human gonadotropin (Pergonal LH/FSH, 1:1) and Lupron, a GnRH agonist, on proliferation of an ovarian cancer cell line, 2774, which is estrogen receptor negative and grows well in serum-free, defined medium. Pergonal, 10 IU/mL or 30 IU/mL, did not enhance cell proliferation, which argues against stabilization of ovarian tumors in vivo due to decreased serum gonadotropin. Lupron, 1.4 micrograms/mL and 140 micrograms/mL, retarded cell division by day 6-8 of culture, in a dose-dependent manner. Flow cytometric cell cycle phase DNA analysis demonstrated Lupron caused a reversible 5-6% increase in the portion of cells in rest phase, G0/G1, compared to controls during log growth, and a corresponding decrease in the portion of cells in DNA synthesis, S phase. However, long-term culture, 3 weeks, with Lupron failed to arrest cells in G0/G1, and experimental cultures plateaued at cell number similar to control cultures. We conclude Lupron's effect on ovarian cancer cell proliferation is independent of gonadotropin and steroid, involves a cell cycle regulatory event, and duration of benefit observed in vivo for some patients may be related to total tumor volume at the time of treatment.

Topics: Antineoplastic Agents; Carcinoma; Cell Division; Cell Transformation, Neoplastic; Culture Media; DNA, Neoplasm; Female; Flow Cytometry; Follicle Stimulating Hormone; G1 Phase; Gonadotropin-Releasing Hormone; Gonadotropins; Humans; Leuprolide; Luteinizing Hormone; Ovarian Neoplasms; Resting Phase, Cell Cycle; S Phase; Tumor Cells, Cultured

Prostate glands exposed to androgen deprivation with leuprolide +/- flutamide were evaluated for pathologic changes which might be related to therapy. Comparing pretreatment and posttreatment tissue by visual discrimination using light microscopic study revealed treatment-related alterations in the size and distribution of neoplastic glands in 60% of cases. Quantitative measurements documented glandular changes in an even greater percentage of cases. Although distinctive, the histologic pattern was not specific for leuprolide/flutamide. The absence of appreciable degeneration and necrosis in tumor cells suggests that this type of androgen deprivation may act through suppression rather than ablation of prostatic cancers. The relationship between treatment-related histologic effects and initial tumor grade and clinical stage as well as expression of prostate-specific antigen was studied. Accurate histologic assessment of leuprolide/flutamide-treated prostate glands should not be a problem so long as specimens are thoroughly examined and drug-related variations in tumor morphologic features are appreciated.

Topics: Aged; Androgens; Antineoplastic Agents; Carcinoma; Combined Modality Therapy; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Humans; Immunoenzyme Techniques; Leuprolide; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms

Leuprolide acetate, a gonadotropin-releasing hormone analogue, produced a variety of beneficial therapeutic responses in five patients with ovarian carcinoma. Four patients had failed intensive chemotherapy with alkylating agents, cisplatin, and Adriamycin. All had one or more clinical conditions that precluded treatment with cytotoxic agents and characteristics associated with resistance to hormone therapy. Our findings support evaluation of expanded eligibility criteria for new hormonal therapy in cases of refractory ovarian carcinoma.

Topics: Antineoplastic Agents; Carcinoma; Female; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Ovarian Neoplasms; Pituitary Hormone-Releasing Hormones

Topics: Androgen Antagonists; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Carcinoma; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Prostatic Neoplasms; Triptorelin Pamoate

From June 1982 to February 1985, 53 patients with stage D2 carcinoma of the prostate confirmed by tissue biopsy, elevated prostatic acid phosphatase and a positive bone scan were initiated on androgen deprivation therapy. Before commencement of treatment all patients underwent determination of serum testosterone levels at 8 a.m. Of the patients 23 received 200 mcg. buserelin per day, 17 received 1 mg. diethylstilbestrol 3 times daily, 6 received 40 mg. megestrol acetate 4 times daily, 2 received 1 mg. leuprolide per day and 5 underwent bilateral orchiectomy. Evaluation of the best response in each patient revealed 3 (6 per cent) complete and 17 (32 per cent) partial responses, while 22 patients (41 per cent) remained stable and 11 (21 per cent) had progression. Pre-treatment serum testosterone levels ranged from 150 to 879 ng. per dl. The mean serum testosterone level in patients having a complete response was 524 +/- 18.04 ng. per dl. The mean in the progression group was 279.4 +/- 110.1 ng. per dl. This difference was not statistically significant owing to the large standard deviation in the progression group. However, of the 15 patients who had a pre-treatment serum testosterone level of more than 500 ng. per dl. only 1 (7 per cent) had progression. None of the patients whose pre-treatment testosterone level was less than 200 ng. per dl. had objective tumor regression. Our study suggests that pre-treatment serum testosterone levels may predict the probability of a satisfactory response to androgen deprivation therapy.

Topics: Aged; Aged, 80 and over; Buserelin; Carcinoma; Diethylstilbestrol; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Megestrol; Megestrol Acetate; Middle Aged; Orchiectomy; Prostatic Neoplasms; Testosterone

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

Bilateral orchiectomy was performed as secondary endocrine treatment in 12 patients with prostatic cancer who were treated initially with a gonadotropin-releasing hormone analogue. Compared to a control group of prostatic cancer patients undergoing orchiectomy as primary therapy, the testes in the hormonally treated group showed marked spermatogenic suppression, peritubular membrane thickening and decreased numbers of Leydig cells. The degree of fibrosis and the damage seen in these testes imply that the spermatogenic suppression seen after prolonged gonadotropin-releasing hormone analogue administration may not be as reversible as previously suggested.

Topics: Aged; Antineoplastic Agents; Carcinoma; Castration; Combined Modality Therapy; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Leydig Cells; Male; Middle Aged; Prostatic Neoplasms; Spermatogenesis; Testis; Time Factors

Leuprolide is a new, potent analogue of gonadotropin releasing hormone, which lowers serum gonadotropins and testosterone with chronic administration. Thirty patients with metastatic carcinoma of the prostate have undergone primary endocrine treatment with leuprolide. Subjective and objective response rates appear to be equal to alternative endocrine therapy, although the mean response duration has not been defined to date. Since castration and the side effects of oral estrogens are avoided leuprolide may prove to be the preferred initial hormonal therapy for selected patients with metastatic prostatic cancer.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents; Carcinoma; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Middle Aged; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms

The histologic appearance of the testes of men exposed to chronic gonadotropin-releasing hormone agonist (GnRH-A) therapy has not been previously documented. Herein, we report on the histologic features of the testes of four patients with disseminated prostatic carcinoma who received at least 1 year of daily treatment with (D-Leu6, des-Gly-NH2(10), proethylamide9)-GnRH (leuprolide, Abbott Laboratories, North Chicago, IL) for their disease, and subsequently underwent bilateral orchiectomy. In marked contrast to the testes from five control patients, the testes of these agonist-treated patients demonstrated absence of spermatogenesis, Leydig cell hypoplasia, and Leydig cell inactivity. These data provide direct histologic evidence that the chronic administration of GnRH agonists may be suitable as a potential male contraceptive.

Topics: Aged; Antineoplastic Agents; Carcinoma; Contraceptive Agents, Male; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Leydig Cells; Luteinizing Hormone; Male; Microscopy, Electron; Middle Aged; Prostatic Neoplasms; Spermatogenesis; Testis; Testosterone; Time Factors