leuprolide and Bone-Neoplasms

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

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

Most cases of advanced carcinoma of the prostate are hormonosensitive. The use of combined androgen blockade (CAB) seems to improve survival and quality of life, but only when combined with chemical castration by luteinizing-hormone-releasing hormone analog and without the use of steroidal antiandrogens. After CAB, further hormonal treatments remain efficacious, such as antiandrogen withdrawal followed by estrogens, aromatase inhibitors, and hormone-refractory prostate cancer multiple cytotoxic agents. For painful bone lesions, external beam radiotherapy, biphosphonates, and strontium 89 or samarium 153 provide pain relief. The use of new methods for the evaluation of response and quality of life will allow the rapid identification of effective treatments and permit powered phase III trials.

Topics: Androgen Antagonists; Bone Neoplasms; Brachytherapy; Combined Modality Therapy; Estrogens; Humans; Leuprolide; Male; Pain; Patient Care Planning; Prostatic Neoplasms; Quality of Life; Radiotherapy; Strontium Radioisotopes

Procollagen 1 amino-terminal propeptide (P1NP) is a bone formation marker and has been shown to have a strong association with the extent of bone metastases (BM) in patients with advanced prostate cancer. More recently, its levels were found to be affected by androgen deprivation therapies and bisphosphonates. We investigated the role of P1NP as a surrogate marker of sub-radiological skeletal metastases in prostate cancer patients with biochemical failure (BF).. BePrepared is a prospective longitudinal substudy of RADAR trial in which serial P1NPs were collected at regular intervals for 123 patients who had completed RADAR protocol treatment.. There was no trend identified in P1NP levels prior to diagnosis of BM. We found that there was no difference in P1NP concentrations at the time of diagnosis of BM in the group that developed BM compared with P1NP levels in groups with only nodal metastases or BF. In the group of patients who did not experience BF, P1NP was affected by previous luteinizing hormone-releasing hormone-agonist and bisphosphonate therapy. Hence, patients who received an 18-month course of androgen deprivation without bisphosphonates had significantly higher P1NP values than patients with shorter androgen deprivation therapy (ADT) course combined with a course of bisphosphonates.. P1NP is not a sensitive serum marker of early BM in high-risk prostate cancer patients with BF and low prostate-specific antigen levels as its levels are affected by prior history of bone remodelling therapies such as ADT and bisphosphonates.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Density Conservation Agents; Bone Neoplasms; Diphosphonates; Drug Therapy, Combination; Early Detection of Cancer; Humans; Imidazoles; Leuprolide; Male; Middle Aged; New South Wales; Peptide Fragments; Prevalence; Procollagen; Prostatic Neoplasms; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Survival Rate; Treatment Outcome; Zoledronic Acid

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

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

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 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

Prostate specific antigen (PSA), prostatic acid phosphatase and alkaline phosphatase were analyzed in 2 large prospective multicenter and multinational trials to assess their correlation with time to progression and overall survival after hormonal therapy for metastatic carcinoma of the prostate.. A total of 868 patients who underwent medical or surgical castration was randomized to receive an oral antiandrogen (nilutamide) or placebo. The serum markers under study were measured at baseline and at 1, 3, 6 and every 6 months thereafter.. At baseline the strongest predictive factor was serum alkaline phosphatase. Patients with an alkaline phosphatase of 2 or less times normal lived almost twice as long as those with a level of more than 2 times normal (p < 0.0001). The longer survival was observed in patients whose PSA became normal 3 months after initiation of hormonal therapy compared to those whose PSA never reached normal (p < 0.0001).. Serum markers at baseline and during the few months after initiation of hormonal therapy can provide prognostic information for the clinical treatment of patients with metastatic carcinoma of the prostate. In addition, the PSA level at month 3 can serve as a surrogate end point in clinical trials.

Topics: Acid Phosphatase; Alkaline Phosphatase; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Neoplasms; Disease Progression; Disease-Free Survival; Humans; Imidazoles; Imidazolidines; Leuprolide; Male; Multivariate Analysis; Orchiectomy; Prognosis; Prospective Studies; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Time Factors

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

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

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

In a preliminary multicentre clinical trial of 3.75 mg leuprorelin acetate depot 18 previously untreated patients with metastatic prostatic cancer were treated with the depot given subcutaneously once every 4 weeks for 28 weeks. Patients also received 100 mg nilutamide taken orally three times a day for the first 14 days of treatment to prevent flare-up. Leuprorelin acetate suppressed the serum testosterone concentration to castration levels; luteinizing hormone levels were also suppressed. The incidence of progressive disease was low and partial response occurred in five patients after treatment. No side-effects were assigned to the flare-up period. It is concluded that leuprorelin acetate depot is a safe and efficacious treatment for metastatic prostatic cancer.

Topics: Aged; Antineoplastic Agents; Bone Neoplasms; Clinical Trials as Topic; Delayed-Action Preparations; France; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Multicenter Studies as Topic; Prostatic Neoplasms; Testosterone

In order to test the hypothesis of complete androgen blockade for advanced prostate cancer (D2CaP), an intergroup trial was instituted in 1985 comparing leuprolide (L) alone to the combination of L with flutamide (F). Eligibility requirements included previously untreated histologically confirmed stage D2CaP, measurable bone or soft tissue metastases, performance status (PS) of 3 or better, acceptable renal and hepatic function, no severe cardiac disease, and no prior or concomitant endocrine therapy. Stratification at entry was on the basis of PS and none or minimal disease (MD) versus severe degree (SD) of bone metastases. Six hundred and seventeen patients were entered into this study between March 1985 and April 1986. At the present time, there is a 3-month difference in the median progression-free survival (13.9 vs 16.9 months; P = 0.039) and a 7.1-month difference in survival (27.9 vs 35.01 months; P = 0.035) favoring L + F. In L + F-treated patients with good PS-MD, the median survival recently has been reached and is 51.9 months vs 39.6 months for L + P patients. The 107 black patients in the study had median survival of 26.4 months vs 33.3 months for whites. Discussions of racial differences in survival as well as other prognostic factors will be presented. The combination of L + F is superior to treatment with L alone. The benefits appear greatest in patients with minimal disease.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Drug Evaluation; Flutamide; Gonadotropin-Releasing Hormone; Hormones; Humans; Leuprolide; Male; Prostatic Neoplasms; Survival Analysis; United States

The mechanisms of metastatic progression from hormonal therapy (HT) are largely unknown in luminal breast cancer. Here we demonstrate the enrichment of CD133(hi)/ER(lo) cancer cells in clinical specimens following neoadjuvant endocrine therapy and in HT refractory metastatic disease. We develop experimental models of metastatic luminal breast cancer and demonstrate that HT can promote the generation of HT-resistant, self-renewing CD133(hi)/ER(lo)/IL6(hi) cancer stem cells (CSCs). HT initially abrogates oxidative phosphorylation (OXPHOS) generating self-renewal-deficient cancer cells, CD133(hi)/ER(lo)/OXPHOS(lo). These cells exit metabolic dormancy via an IL6-driven feed-forward ER(lo)-IL6(hi)-Notch(hi) loop, activating OXPHOS, in the absence of ER activity. The inhibition of IL6R/IL6-Notch pathways switches the self-renewal of CD133(hi) CSCs, from an IL6/Notch-dependent one to an ER-dependent one, through the re-expression of ER. Thus, HT induces an OXPHOS metabolic editing of luminal breast cancers, paradoxically establishing HT-driven self-renewal of dormant CD133(hi)/ER(lo) cells mediating metastatic progression, which is sensitive to dual targeted therapy.

Topics: AC133 Antigen; Anastrozole; Androstadienes; Animals; Antigens, CD; Antineoplastic Agents, Hormonal; Bone Neoplasms; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Cell Line, Tumor; Cell Self Renewal; Drug Resistance, Neoplasm; Estradiol; Female; Flow Cytometry; Fulvestrant; Gene Expression Regulation, Neoplastic; Glycoproteins; Humans; In Vitro Techniques; Interleukin-6; Letrozole; Leuprolide; MCF-7 Cells; Mice, Inbred NOD; Mice, SCID; Neoplasm Metastasis; Neoplasm Transplantation; Neoplastic Stem Cells; Nitriles; Oxidative Phosphorylation; Peptides; Real-Time Polymerase Chain Reaction; Receptor, Notch3; Receptors, Estrogen; Receptors, Notch; Signal Transduction; Tamoxifen; Triazoles

To report the outcome and course of disease in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line docetaxel followed by abiraterone acetate in a single center.. In this retrospective observational study, we reviewed the course of disease of all applicable patients with mCRPC treated with docetaxel followed by abiraterone at our center. We analyzed progression-free survival (PFS) of docetaxel and abiraterone treatments. We further searched for predictive factors for the duration of treatment response.. Median PFS between initiation of androgen deprivation therapy and the diagnosis of mCRPC was 32 months. Median PFS on docetaxel treatment was 9 months. Median PFS on abiraterone treatment was 11 months. Patients with higher Gleason scores (GS) (8-10) at initial diagnosis had a significantly longer median PFS on docetaxel as compared to patients with GS 6-7, p = 0.01. We demonstrate a significant correlation between the PFS on docetaxel and PFS on abiraterone in the post-docetaxel setting (Kendall tau r = 0.32, p = 0.019) as well as a significant negative correlation between the PSA nadir under abiraterone treatment and the time to progression under abiraterone (Kendall tau r = -0.43, p = 0.007).. High Gleason score appears to be predictive of duration of response to docetaxel. Interestingly, progression-free survival with abiraterone appears to be correlated with the duration of response with docetaxel, whereas PSA decline and low nadir appear to be predictive of response to abiraterone.

Topics: Aged; Androgen Antagonists; Androstenes; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Cohort Studies; Disease-Free Survival; Docetaxel; Flutamide; Humans; Leuprolide; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Nitriles; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Taxoids; Tosyl Compounds; Treatment Outcome; Triptorelin Pamoate

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; 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

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

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

Case 1: A 34-year-old woman,who had a right breast cancer with axillary lymph node metastasis and multiple bone metastases, was referred to our clinic. She developed paralysis of lower extremities and disorder of the bladder and rectum due to metastasis to the thoracic vertebra, and also had renal dysfunction due to severe hypercalcemia and hemorrhagic cystitis. Correcting the serum calcium level with intravenous infusion, elcatonin, pamidronate and betamethasone, she underwent radiation therapy for the vertebral metastasis. The first hormonal therapy (leuprorelin/exemestane) had been effective for about 4 months, however the second hormonal therapy (leuprorelin/tamoxifen) was not effective. Chemotherapy with paclitaxel (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about a stable general condition and a normal level of serum calcium with zoledronate in the ninth month of treatment. Case 2: A 32-year-old woman, who had a right breast cancer with multiple bone metastases and axillary and hilar lymph node metastases, came to our clinic, complaining of nausea due to severe hypercalcemia. After successful correction of hypercalcemia by the intravenous infusion and administration of elcatonin, pamidronate and dexamethasone, the hormonal therapy(goserelin/tamoxifen) caused rapid re-elevation of serum calcium and tumor marker, so that a tumor flare was suspected. After 3 cycles of EC therapy (EPI 90 mg/m(2), CPM 600 mg/m(2), every 3 weeks), 2 cycles of paclitaxel therapy (80 mg/m(2), day 1, 8, 15, every 4 weeks) brought about tumor reduction and the normal level of serum calcium. After 7 cycles of paclitaxel therapy,the hormonal therapy (goserelin/tamoxifen) proved effective for several months. To achieve tumor reduction and stabilize the serum calcium level, we need to start immediately the treatment of breast cancer with severe hypercalcemia, considering the general condition of the patient.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Drug Administration Schedule; Female; Goserelin; Humans; Hypercalcemia; Imidazoles; Leuprolide; Lymph Nodes; Lymphatic Metastasis; Paclitaxel; Quality of Life; Tamoxifen; Zoledronic Acid

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

Topics: Anastrozole; Androstadienes; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Bone Neoplasms; Breast Neoplasms, Male; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Humans; Letrozole; Leuprolide; Lung Neoplasms; Lymphatic Metastasis; Male; Mastectomy, Modified Radical; Middle Aged; Nitriles; Receptors, Estrogen; Receptors, Progesterone; Treatment Outcome; Triazoles

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

A 42-year-old woman with multiple organ metastases from breast cancer was successfully treated with 5'-deoxy-5-fluorouridine (5'-DFUR) and hormonal therapy (leuprorelin+tamoxifen). She underwent radical mastectomy for advanced left breast cancer in June 1998. In September 2000, she was treated with docetaxel for multiple lung metastases, and the lesions were diagnosed as in complete remission. In June 2001, she received radiation for bone metastasis in left femoral and received a resection of subcutaneous metastases in the face. Then she received 2 courses of paclitaxel. In May 2002, she had multiple lung metastases, right adrenal metastasis, tumor thrombus in the inferior vena cava and multiple bone metastases, and was treated with cycrophosphamide, epirubicin, and 5-FU, however, they were abandoned due to severe leucopenia. Therefore, 600 mg/day of 5'-DFUR was administered from December 2002. The lesions of lung and adrenal decreased extendedly in March 2003. She was diagnosed as being in CR in March 2004, and this condition has continued to the present.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoma, Papillary; Combined Modality Therapy; Cyclophosphamide; Drug Administration Schedule; Epirubicin; Female; Floxuridine; Follow-Up Studies; Humans; Leuprolide; Lung Neoplasms; Mastectomy, Radical; Neoplastic Cells, Circulating; Tamoxifen; Vena Cava, Inferior

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

A 78-year-old man admitted with clinical jaundice and pelvic pain had a total bilirubin level of 6.56 mg/dL, an alkaline phosphatase level of 855 U/L, and a prostate specific antigen (PSA) level of 9996 ng/mL. A computed tomogram demonstrated marked retroperitoneal, peripancreatic, periceliac, and periaortic lymphadenopathy. A bone scan revealed increased radiolabeled technetium uptake in the pelvis, vertebral column, parietooccipital region, ribs, and appendiceal skeleton. A biopsy of one pelvic lesion revealed metastatic prostate cancer. This man's obstructive jaundice and bone pain had a dramatic response to treatment with a gonadotropin-releasing hormone analog (leupro lide) and antiandrogen (bicalutamide). All bone pair and clinical signs of jaundice disappeared in 1 week His total bilirubin decreased to 0.84 mg/dL by 2 weeks His PSA values reflected this clinical response, decreasing to 4022 ng/mL in 1 week, 2680 ng/dL after 2 weeks and 1028 ng/mL after 1 month of the above therapy.

Topics: Aged; Alkaline Phosphatase; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bilirubin; Bone Neoplasms; Cholestasis; Humans; Leuprolide; Lymphatic Metastasis; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Tosyl Compounds; 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

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

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

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

The scintigraphic "flare" phenomenon on bone imaging refers to an increase in intensity of tracer uptake in sites of bone metastases and/or the appearance of "new" lesions, which occur shortly after commencement of hormonal therapy or chemotherapy for breast, prostate, or lung cancer. In this study, we observed that scintigraphic flare can occur in patients with prostate cancer following treatment with the "hormone-like" luteinizing hormone releasing hormone analog, leuprolide acetate. Twenty-six patients with prostate cancer being treated with leuprolide acetate underwent serial bone scans at three-month intervals. Five (19.2%) of the 26 patients had findings consistent with a scintigraphic flare on bone scans obtained between three and six months after initiation of therapy. These scan findings should not be confused with progression of skeletal metastases.

Topics: Antineoplastic Agents; Bone Neoplasms; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Prostatic Neoplasms; Radionuclide Imaging; Technetium Tc 99m Medronate

Serial measurements of urinary hydroxyproline excretion were performed in 16 patients with stage D2 prostatic cancer to evaluate its role as a marker for following disease course. Patients were defined as having stable or progressive disease by the criteria of the National Prostatic Cancer Project. For patients with stable disease and those with disease progression excretion of hydroxyproline did not correlate with the clinical course. We did not find that hydroxyproline was a useful marker in the clinical setting to follow patients with prostatic cancer.

Topics: Bone Neoplasms; Buserelin; Creatinine; Flutamide; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Hydroxyproline; Leuprolide; Male; Prostatic Neoplasms

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

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

Metastatic prostatic cancer generally is treated by either castration or the administration of exogenous estrogens, both of which have significant clinical disadvantages. Luteinizing hormone releasing hormone analogues have been shown to suppress gonadal steroidogenesis in animals and humans. To assess the effect of the administration of a potent luteinizing hormone releasing hormone analogue, (D-Leu-6)luteinizing hormone releasing hormone (1-9) nonapeptide ethylamide, 9 patients with previously untreated stage D2 prostatic cancer were treated with this agent for 3 to 8 months. By 3 months of treatment all patients demonstrated a significant decrease in serum testosterone and a decreased peak serum luteinizing hormone and testosterone response to the acute administration of the analogue, with no change in baseline serum luteinizing hormone or prolactin. These data suggest that this analogue acts by decreasing the pituitary release of luteinizing hormone. No major adverse effects were noted with this treatment modality, and all patients were symptomatically improved and demonstrated a decrease or stabilization in tumor activity as measured by prostatic computerized tomography or ultrasound scan, prostatic acid phosphatase and bone scan. A representative case is presented. Luteinizing hormone releasing hormone analogues may prove to be valuable new agents in the treatment of advanced prostatic cancer.

Topics: Aged; Bone Neoplasms; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Lymphatic Metastasis; Male; Middle Aged; Prostatic Neoplasms; Tomography, X-Ray Computed