goserelin 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

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

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

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

The treatment of patients with recurrent ovarian carcinoma after failure of first and second-line chemotherapy is still debated. Chemical agents used for third and fourth-line therapy usually yield poor results with severe toxic side effects.. To summarize our experience with goserelin in the treatment of patients with recurrent ovarian cancer.. From September 1996 to June 1999 we administered goserelin, 3.6 mg subcutaneously every 4 weeks, to 15 patients with advanced and recurrent epithelial ovarian cancer (median age 59.0, median performance status 3.0).. Seven of 15 eligible patients relapsed after platinum-based chemotherapy (3 of them also received paclitaxel and another 2 received tamoxifen). Four patients relapsed after carboplatin and paclitaxel, one of whom was treated with topotecan thereafter. Two patients relapsed after single-agent paclitaxel. Two patients with advanced disease and poor performance status without previous treatment received only goserelin. There was one complete response (6.7%) and 1 partial response (6.7%) lasting 8 and 14 months respectively (overall response rate 13.4%). In addition, the disease stabilized in three patients (20%) for a median of 7.5 months. In 10 patients the disease progressed. There was no significant toxicity. Median survival of all patients was 5.8 months.. Goserelin was helpful in one-third of our patients with advanced and refractory ovarian cancer. It is an easy and non-toxic option for treating very ill or previously heavily treated patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Carcinoma; Female; Goserelin; Humans; Middle Aged; Neoplasm Recurrence, Local; Ovarian Neoplasms; Treatment Failure

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Hypocalcemia is a rare complication of malignancy. We present the case of a 30-year-old lady presenting with a grand mal seizure due to profound hypocalcemia. She was subsequently found to be hypoparathyroid and was diagnosed with metastatic breast carcinoma. Treatment with goserelin and exemestane produced a significant reduction in her tumor load and a correction of her hypocalcemia, which was initially refractory to treatment. We believe this to be the first case of metastatic breast carcinoma actually presenting with hypocalcemia and feel that clinicians should be aware of this rare complication.

Topics: Adult; Androstadienes; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Carcinoma; Epilepsy, Tonic-Clonic; Female; Goserelin; Humans; Hypocalcemia; Neoplasm Metastasis

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

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

There are trials comparing different neoadjuvant chemotherapy regimens for locally advanced primary breast cancer (LAPC). Few studies have evaluated alternative therapeutic approaches towards LAPC. A previous trial from our institute in LAPC patients unselected for oestrogen receptor (ER) status, comparing primary endocrine therapy versus multimodal treatment, showed no difference in breast cancer related deaths or overall survival. We report our experience of primary endocrine therapy in ER+ LAPC.. Between 1988 and 2007, 195 ER+, non-inflammatory LAPC patients were treated with primary endocrine agents in our institute, due to patient choice, being unfit for chemotherapy, or recruitment into the above mentioned trial. All patients had disease assessable by UICC criteria.. Median age was 69 years. The median follow-up was 61 months. 154 patients (79%) received endocrine treatment alone. 185 patients (95%) derived clinical benefit (complete response/ partial response/ stable disease) for > or =6 months from primary endocrine therapy. Overall 5-year survival was 76% and 5-year breast cancer specific survival was 86%.. In selected group of ER+ LAPC patients, primary endocrine treatment achieves excellent survival outcome and is a viable alternative to other modalities of treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma; Combined Modality Therapy; England; Estrogen Receptor Modulators; Estrogens; Female; Goserelin; Humans; Middle Aged; Neoplasms, Hormone-Dependent; Randomized Controlled Trials as Topic; Receptors, Estrogen; Retrospective Studies; Survival Rate; Tamoxifen; Treatment Outcome

Telomerase is a ribonucleoprotein complex that protects the ends of chromosomes from degradation. Its catalytic subunit, hTERT, controls its activity. Prior data in prostate carcinoma cases indicated that immunohistochemical hTERT reactivity increases with tumor grade and may be absent in lower grade cases. The effect of complete androgen ablation (CAA) on tumor hTERT expression was uncertain.. hTERT immunostaining was performed on the cancerous pretreatment biopsy tissue of 30 men who consecutively underwent CAA with bicalutamide and goserelin acetate for 30 days prior to undergoing radical prostatectomy, and on their tumor tissue from radical prostatectomy. As controls, biopsy and prostatectomy samples from 30 untreated men were studied. Nuclear staining was evaluated by two observers, and the change in staining between biopsy and prostatectomy samples was evaluated using the Student t test in both groups.. The percent of reactive tumor nuclei in treated men declined from 36.7% to 13.2% (P = 0.0001), and declined from 19.8% to 16.1% in untreated men (P = 0.4). The greater mean hTERT reactivity in the treated men's biopsy specimens was attributed to an increased proportion of higher (Gleason score > or = 7) grade tumors. The decline in hTERT immunostaining remained significant after normalizing it to that of the untreated group (P = 0.002). The original Gleason scores, corresponding declines in the percentage of reactive tumor nuclei, and significance were: Gleason score < or = 6: 11% (P = 0.03); Gleason score of 7: 23% (P < 0.006); and Gleason score > or = 8: 46% (P < 0.005) (from a mean 63% to 17%).. CAA for prostate carcinoma can be considered an antitelomerase therapy. The steepest reduction in telomerase activity was noted in the highest grade tumors.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Carcinoma; Catalytic Domain; Goserelin; Humans; Immunohistochemistry; Male; Middle Aged; Nitriles; Peptide Fragments; Prostatectomy; Prostatic Neoplasms; Telomerase; Tosyl Compounds

The aim of this study was to retrospectively compare the clinical outcomes achieved in 2 groups of patients with cT3 prostatic carcinoma undergoing neoadjuvant hormonotherapy and neoadjuvant hormonotherapy plus adjuvant hormonotherapy with external beam radiotherapy.. One hundred patients with cT3N0M0 prostatic carcinoma underwent radiotherapy to pelvic lymph nodes (45 Gy, 1.8 Gy/fraction) with a booster dose (65-70 Gy) to the prostatic cavity. Forty-four patients received neoadjuvant hormonotherapy (goserelin, starting 2 months before radiotherapy and continuing until the end of irradiation); 56 patients received neoadjuvant hormonotherapy plus adjuvant goserelin until disease progression, if present.. Patients undergoing adjuvant hormonotherapy as compared to those who received exclusive neoadjuvant therapy showed a higher reduction in PSA level below 1.0 ng/ml (p = 0.0211), a lower incidence of biochemical failures (p = 0.0170), a lower incidence of hematogenous metastases (p = 0.0320) and a trend suggestive of a better disease-free survival (p = 0.0660). At univariate analysis (logrank), Gleason score did not show a significant correlation with any of the end points analyzed. To the contrary, patients with tumor <15 mm showed a better local control (p = 0.0347) and biochemical failure-free survival (p = 0.0102). Furthermore, a trend between initial PSA level and incidence of hematogenous metastases was observed (p = 0.0519). Patients with a posttreatment PSA level <1.0 ng/ml had a lower incidence of metastases (p = 0.0237) and a better survival (p = 0.0178); patients with complete clinical response showed a lower incidence of biochemical failures (p = 0.0469). Radiotherapy doses >70 Gy showed a trend with biochemical failure-free survival (p = 0.0554). At multivariate analysis, a correlation between Gleason score and incidence of metastases (p = 0.0232), and between tumor diameter and local control (p = 0.0178) and biochemical failure-free survival (p = 0.0290) was recorded.. In patients with cT3N0M0 prostate carcinoma, prolonged hormonotherapy was shown to be significantly correlated with biochemical failure-free survival and distant metastasis-free survival. Furthermore, tumor size had a significant impact on biochemical failure-free survival as well as on local control.

Topics: Antineoplastic Agents, Hormonal; Carcinoma; Chemotherapy, Adjuvant; Goserelin; Humans; Male; Middle Aged; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Retrospective Studies

We report 3 patients referred to the bone clinic after spinal fractures. Dual energy X-ray absorptiometry showed severe osteoporosis. Each patient was found to have a history of prostatic carcinoma and long-term treatment with goserelin. We suggest that all patients who have received androgen deprivation therapy for more than 1 year should be evaluated by bone densitometry.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Carcinoma; Densitometry; Femoral Fractures; Follow-Up Studies; Fractures, Spontaneous; Goserelin; Humans; Male; Osteoporosis; Prostatic Neoplasms; Risk Assessment; Severity of Illness Index; Spinal Fractures; Thoracic Vertebrae

We report a case of the numb chin syndrome as the presenting symptom in a patient with metastatic prostate carcinoma. The numb chin syndrome is characterized by facial numbness along the distribution of the mental branch of the trigeminal nerve. Most cases of this syndrome that are not dental in origin have been associated with diffuse metastatic disease, particularly with underlying lymphoproliferative and breast cancer. Although axial and vertebral bone metastases are common in patients with carcinoma of the prostate, mental nerve involvement is rare. We present a case of the numb chin syndrome as the initial clinical manifestation in a patient with metastatic prostate adenocarcinoma.

Topics: Aged; Antineoplastic Agents, Hormonal; Biopsy; Carcinoma; Chin; Drug Therapy, Combination; Flutamide; Goserelin; Humans; Hypesthesia; Male; Prostate-Specific Antigen; Prostatic Neoplasms; Syndrome

Inappropriate antidiuretic hormone secretion (SIADH) may occur in a variety of diseases, including malignancies, and can be induced by drugs. We report a case of SIADH associated with prostatic carcinoma. A 50-year-old man was admitted to hospital with severe flank pain and weight loss. The diagnosis of SIADH syndrome and prostatic carcinoma was established, and hormonal therapy was instituted. However, the patient died in a month without any response to therapy. We conclude that prostatic carcinoma may cause SIADH and should therefore be considered in the differential diagnosis.

Topics: Abdominal Pain; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Diagnosis, Differential; Fatal Outcome; Goserelin; Humans; Inappropriate ADH Syndrome; Male; Middle Aged; Nitriles; Paraneoplastic Syndromes; Prostatic Neoplasms; Tosyl Compounds; Weight Loss

In order to evaluate the prognostic value of tissue-PSA (prostatic-specific protein, measured in aspiration biopsies) 231 hormonally treated patients with verified carcinoma of the prostate (CaP) but without metastasis were studied retrospectively. T-PSA was determined at the time of diagnosis in all patients and in 52 of these also at 6, 12 and 24 months after diagnosis. Of the 231 patients, 79 died of prostatic carcinoma and 152 were still alive or had died of other diseases at the end of the observation period (more than 71 months). In a first set of evaluations the predictive value of a single analysis at the time of diagnosis was studied in 179 patients. It was found that tissue PSA was the most important factor for predicting both time to progression and time to death in CaP. Other competing factors were S-PSA, free S-PSA, age, clinical stage, grade and DNA-ploidy. Further evaluations regarding serial PSA determinations were performed in 52 patients. Tissue PSA increased during treatment in all patients who died of CaP. In all patients who survived or died for other reasons, tissue PSA decreased during treatment and remained low. The change of tissue PSA seen between 0, 6 and 12 months could in all cases predict the clinical outcome. It is concluded that a single analysis of tissue PSA at the time of diagnosis can predict the clinical outcome in most cases and that serial determinations can predict the outcome in almost all cases of a CaP without metastasis at the time of diagnosis. This requires that we use this assay when selecting between patients who will survive on hormonal treatment and those who most probably would benefit from a more aggressive treatment.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Biopsy, Needle; Carcinoma; Estradiol; Estradiol Congeners; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Treatment Outcome

Androgen receptor blocking agents have become an established form of therapy for men with disseminated prostate carcinoma. The purpose of this study was to evaluate markers of bone turnover and to measure bone mineral densities (BMD) in men with disseminated prostate carcinoma treated with combined androgen blockade prior to and after 6 months of intermittent cyclic etidronate therapy.. Twelve consecutive men with disseminated prostate carcinoma were evaluated at 0, 6, and 12 months after treatment with a long acting gonadotropin-releasing hormone agonist (goserelin acetate) and an androgen antagonist (flutamide). During the 6-12 month period, patients were treated with adjuvant intermittent cyclic etidronate therapy and calcium supplementation. Lumbar spine BMD was measured by spinal quantitative computed tomography (QCT) and femoral neck BMD by dual energy X-ray absorptiometry (DXA).. Combined androgen blockade resulted in all men achieving serum free testosterone concentrations of <2.2 pmol/L (normal range, 38-114 pmol/ L). The mean serum prostate specific antigen activities decreased from 130.8+/-46 to 6.9+/-4.4 ng/mL (P < 0.05). Although serum calcium, parathyroid hormone, and 25-hydroxyvitamin D measurements remained unchanged, serum bone Gla-protein concentrations and urinary deoxypyridinolene excretion rates increased significantly (P < 0.01, respectively). Mean lumbar spine QCT decreased by 6.6+/-1.5% from 76.5 mg/cm3 (95% confidence interval [95% CI, 57-96 mg/cm3) to 73.9 mg/cm3 (95% CI, 55-93 mg/cm3) (P < 0.001) and mean femoral neck DXA decreased by 6.5+/-1.3% from 0.94 g/cm2 (95% CI, 0.81-1.07 g/cm2) to 0.91 g/cm2 (95% CI, 0.79-1.04 g/cm2) (P < 0.001). After treatment with adjuvant intermittent cyclic etidronate, mean lumbar spine QCT increased by 7.8+/-3.7% to a final value of 75 mg/cm3 (95% CI, 48.7-101 mg/cm3) (P=0.001 compared with the initial 6 months without intermittent cyclic etidronate therapy). Significant increases in BMD also were observed in the femoral neck and Ward's triangle.. Androgen receptor blocking agents have an established role in the treatment of disseminated prostate carcinoma. However, combined androgen blockade in elderly men with disseminated prostate carcinoma results in high bone turnover with significant cancellous bone loss. The results of this study show that adjuvant therapy with intermittent cyclic etidronate may prevent these changes and decrease the risk of spinal fractures.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Amino Acids; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bone and Bones; Bone Density; Calcium; Carcinoma; Drug Administration Schedule; Etidronic Acid; Evaluation Studies as Topic; Femur Neck; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Longitudinal Studies; Lumbar Vertebrae; Male; Middle Aged; Osteocalcin; Parathyroid Hormone; Prostate-Specific Antigen; Prostatic Neoplasms; Remission Induction; Testosterone; Tomography, X-Ray Computed; Vitamin D

The usefulness of estramustine phosphate (ECT) for preventing flare-up in goserelin acetate depot therapy for advanced prostate cancer was studied. Pretreatment with ECT 560 mg daily for 3 weeks almost completely prevented the rise in testosterone level seen in goserelin acetate depot therapy and no signs or symptoms of tumor flare were observed. Long-term ECT completely blocked the rise in luteinizing hormone and testosterone level, but ECT at this dosage was likely to cause complications. The administration of ECT 560 mg daily for 3 weeks prior to goserelin acetate depot therapy was considered sufficient to prevent tumor flare, and its effect was considered to be more marked than that of short-term treatment with antiandrogens.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Carcinoma; Disease Progression; Drug Therapy, Combination; Estramustine; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone

We have been interested in the possible direct effects of luteinizing hormone releasing hormone (LHRH) and somatostatin (SS) analogs on the growth of human mammary tumor cells. Four recently synthesized peptide hormones including the LHRH agonists D-Trp6-LHRH and zoladex, LHRH antagonists SB30 and SB75, and the somatostatin analog RC 160 were analyzed for their effects on DNA synthesis of MCF-7 breast cancer cells in culture. At 48 hr, D-Trp6-LHRH and SB30 did not show significant effects (dose range, 10(-12)-10(-6) M). However, the combination of these two peptides at 10(-10) M produced significant inhibition of 3[H]thymidine incorporation (50% control). At 72 hr in the absence of estradiol-stimulated growth, D-Trp6-LHRH showed inhibition at 10(-12) and 10(-10) M (P less than 0.005 and 0.001). At higher concentrations, no significant inhibition was noted. In contrast to D-Trp6, SB30 (antagonist) showed no inhibition but significant stimulation of DNA synthesis at 10(-6) and 10(-4) M. In the presence of added estradiol (10(-9) M), complete reversal of D-Trp6-LHRH analog inhibition is noted. In contrast, there is persistent stimulation by SB30 (P less than 0.001). At 96 hr, D-Trp6-LHRH continued to show maximal inhibition of 70% in the absence of estradiol. SB30 stimulated DNA synthesis 100% at 10(-6) M. At 72 hr, the SS analog RC 160 demonstrated significant inhibition (53%) that was similar to D-Trp6 and SB75 peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antineoplastic Agents; Breast Neoplasms; Buserelin; Carcinoma; Cell Division; Estrogens; Gonadotropin-Releasing Hormone; Goserelin; Hormones; Humans; In Vitro Techniques; Somatostatin; Triptorelin Pamoate; Tumor Cells, Cultured

Lymphangitic carcinomatosis of the lung is a late and often fatal manifestation of cancer. We describe a case of a biopsy-proved pulmonary lymphangitic carcinomatosis in an asymptomatic 61-year-old man. The pulmonary picture proved to be the initial sign of a prostatic cancer. Therapy with LH-RH analogues and antiandrogens achieved a complete clearance of lung involvement.

Topics: Buserelin; Carcinoma; Flutamide; Goserelin; Humans; Lung Neoplasms; Lymphangitis; Male; Middle Aged; Prostatic Neoplasms

79 patients with locally advanced and/or metastatic prostate cancer were treated by means of a biodegradeable depot formulation of the luteinizing hormone releasing hormone analogue Goserelin (Zoladex). All patients received 3.6 mg depot Goserelin (Zoladex 3.6 mg implantate) subcutaneously into the anterior abdominal wall at 4 weekly intervals. The average time of observation was 24.2 months. The best objective response rate was found in 62%. Serum testosterone levels initially increased after the first depot injection and then decreased ultimately to castrate range (less than 0.6 ng/ml) between day 15 and day 27 (median 21) in the majority of patients. Castrate testosterone levels were still found 48 months after the start of treatment with depot Goserelin. 6 months after institution of treatment in 66.7% of cases evident signs of histological regression were found in the primary tumour tissue. Adenocarcinoma presented with a highly significantly better response pattern than anaplastic carcinoma. In animal experiments a single dose of 1 mg depot Goserelin was administered to adult male rats and the effect on serum testosterone levels and target organs (testes and ventral prostate) were investigated. Mean testosterone levels (mean = 0.31 ng/ml) decreased to castrate range (less than 0.3 ng/ml). 4 weeks after depot injection weight of the testes and prostate weight were significantly reduced. However 8 weeks after administration of 1 mg depot Goserelin there was no significant between the control group and the treated group. We conclude that the depot formulation of Goserelin (Zoladex) is effective, simple, practicable and safe in the treatment of advanced prostatic cancer. Current clinical studies are confirming the importance of reversible medical castration by LHRH agonists before radical prostatectomy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Animals; Buserelin; Carcinoma; Drug Implants; Goserelin; Humans; Male; Middle Aged; Organ Size; Prospective Studies; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testis; Testosterone

We treated 191 patients with histologically proved locally advanced stage (T3 or T4) and/or metastatic prostate cancer with a biodegradable depot formulation of a luteinizing hormone-releasing hormone analogue (Zoladex). After an initial increase in serum testosterone in week 1 of therapy a continuous decrease of testosterone to castrate levels was obtained. With a monthly injection of the luteinizing hormone-releasing hormone analogue 4 patients (2 per cent) experienced a transient increase in bone pain, 1 had ureteral obstruction and 1 suffered paraplegia during the first few weeks of therapy. Over-all objective and subjective responses were similar to those obtained by castration or estrogen therapy. The absence of local and systemic (long-term) side effects proves the validity of this approach for patients with advanced prostatic cancer.

Topics: Aged; Aged, 80 and over; Buserelin; Carcinoma; Drug Administration Schedule; Goserelin; Humans; Injections, Subcutaneous; Male; Middle Aged; Prostatic Neoplasms; Testosterone

Transrectal ultrasonography has proved valuable in assessing the effect of primary treatment modalities for prostate carcinoma. This study shows patients who had a significant reduction in primary tumor volume had a significantly better prognosis and had less local symptoms than did the group of patients that did not have a significant reduction (less than 50%) in primary volume secondary to therapy. Patients were treated with either castration or Zoladex and all had Stage D2 cancer of the prostate.

Topics: Aged; Buserelin; Carcinoma; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Ultrasonography

Eighty patients with prostatic cancer have been treated with an LH-RH analogue (Zoladex). Ten had no metastasis, and hormone therapy was used as an induction treatment before curative radiotherapy. The others had metastatic disease and, in some cases, had already received some form of endocrine therapy. Patients received a monthly injection of Zoladex (3.6 mg). No progressive disease was noted among patients with nonmetastatic tumors; of the patients with metastases, those who were previously untreated had a higher response rate (14.8% complete response) and longer progression-free and overall survival. Toxicity was mild in spite of two cases of disease flare.

Topics: Aged; Aged, 80 and over; Bone Neoplasms; Buserelin; Carcinoma; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Remission Induction

The depot LH-RH agonist Zoladex was used to treat 38 patients with previously untreated symptomatic stage D2 prostate carcinoma. Side effects were minimal and patient acceptability excellent, although temporary tumor flare occurred in 11% of patients. Eighty-four percent experienced subjective improvement and 87% had objective evidence of initial disease stabilization or remission lasting 3 months. Serum levels of gonadotrophin and free testosterone as well as androgens of adrenal origin fell significantly with treatment. Long-term survival to date appears at least as good as that described for conventional endocrine therapy.

Topics: Buserelin; Carcinoma; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Male; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Remission Induction; Testosterone

We treated 37 patients with newly diagnosed advanced prostatic cancer with monthly injections of a long acting depot preparation of a luteinizing hormone-releasing hormone superagonist. Serum testosterone levels were reduced to and maintained within the castrate range, even in cases of objective progression. The partial objective regression rate was 43 per cent, with 36 per cent of the patients having objectively stable disease and 21 per cent having objective progression. The subjective improvement rate was 67 per cent. The addition of a short course of diethylstilbestrol at the initiation of therapy appeared to shorten the delay for the subjective improvement. Patient acceptance was excellent and side effects were minimal. Depot luteinizing hormone-releasing hormone analogues, alone or in combination, may well become a preferred alternative treatment for patients with advanced prostatic cancer.

Topics: Aged; Buserelin; Carcinoma; Delayed-Action Preparations; Diethylstilbestrol; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Testosterone

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