goserelin and Bone-Neoplasms

Prostate cancer sometimes metastasizes, especially to bone, which may cause pain, fractures and spinal cord compression. What are the best first-line treatment options for patients with metastatic prostate cancer? To answer this question, we conducted a review of the literature, using the standard Prescrire methodology. Suppressing androgen secretion by surgically removing the testicles (orchiectomy) or by administering a gonadorelin agonist relieves the pain associated with bone metastases in about 80% of patients. This treatment has a clear impact on symptoms, despite the lack of clinical trials versus placebo or no treatment. Its impact on overall survival is uncertain. In terms of survival, goserelin therapy appears to have similar efficacy to orchiectomy. The efficacy of other gonadorelin agonists is less well documented. Degarelix, a gonadorelin antagonist, does not appear to provide a therapeutic advantage over gonadorelin agonist. In 2012, oestrogen should not be used in the treatment of metastatic prostate cancer, because of its cardiovascular adverse effects. Antiandrogen monotherapy, preferably with flutamide, appears to be less beneficial than orchiectomy in terms of survival. Overall, adverse effects are more frequent with nonsteroidal antiandrogens than with gonadorelin agonists, but sexual dysfunction is less frequent. Cyproterone, a steroidal antiandrogen, seems to have fewer adverse effects leading to treatment discontinuation than nonsteroidal antiandrogens. There is no firm evidence that starting hormonal therapy before metastases become symptomatic is beneficial. When symptoms have disappeared and the PSA level is low, one option is to temporarily interrupt gonadorelin agonist therapy if it is poorly tolerated, even though this may shorten survival by a few months. The addition of a nonsteroidal antiandrogen to androgen suppression therapy slightly improves 5-year survival, preventing about 3 deaths per 100 patients, but at a cost of additional adverse effects. First-line hormonal treatments are initially very effective in relieving symptoms of metastatic prostate cancer. Our analysis of the available data suggests that the best treatment option is androgen suppression with goserelin. Flutamide monotherapy is an alternative for some patients.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Neoplasms; Cyproterone; Estrogens; Flutamide; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Practice Guidelines as Topic; Prostatic Neoplasms; Time Factors; Treatment Outcome

Bone-targeted treatments with bisphosphonates and denosumab, which reduce bone resorption, are known to reduce the risk of skeletal complications and prevent treatment-induced bone loss in patients with malignant bone disease. Additionally, these drugs may modify the course of bone destruction via inhibitory effects on the "vicious cycle" of growth factor and cytokine signaling between tumor and bone cells within the bone marrow microenvironment. Effects of the drugs on the stem cell niche, direct effects on the cancer cells, and immune modulation may also contribute. In early-stage (stages I, II, and III) breast cancer, treatment with the bisphosphonate zoledronic acid has shown improvements in disease-free and overall survival. Improved survival was particularly notable in women with established menopause at diagnosis and in premenopausal women with endocrine-responsive disease who received treatment with goserelin, which suppresses ovarian function by inhibiting the production of ovarian hormones. Additionally, in castrate-resistant prostate cancer, treatment with denosumab delays the development of bone metastases. These results strongly support the adjuvant use of bone-targeted treatments but suggest that reproductive hormones are an important treatment modifier to take into account. In advanced-stage (stage IV, ie, metastatic) cancers, survival benefits have been observed in patients with multiple myeloma and in patients with other solid tumors with rapid rates of bone destruction who received treatment with zoledronic acid. Here, we have critically reviewed the increasing evidence to support a disease-modifying effect of bone-targeted treatment and discussed the impact on clinical management.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bone Density Conservation Agents; Bone Neoplasms; Breast Neoplasms; Denosumab; Diphosphonates; Disease Progression; Disease-Free Survival; Female; Goserelin; Humans; Imidazoles; Male; Menopause; Neoplasms; Prostatic Neoplasms; Survival Rate; Treatment Outcome; Zoledronic Acid

Management of patients with metastatic prostate cancer differs from that of patients with other metastatic solid tumors. Because the treating physician is usually the patient's urologist, the primary care physician's main role may be to relieve pain and treat the patient for common side effects of hormone therapies. By being familiar with the forms of systemic treatment-including orchiectomy and the use of estrogens, luteinizing hormone-releasing hormone agonists, and antiandrogens-the primary care physician can also assist patients in making treatment decisions that are individualized to the specifics of disease state, comorbid conditions, age, and value systems.

Topics: Antineoplastic Agents, Hormonal; Bone Neoplasms; Estrogens; Goserelin; Humans; Male; Orchiectomy; Pain Management; Palliative Care; Prostatic Neoplasms

This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer.. Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks.. A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P < 0.001). Median time to biochemical progression for patients with serum bone-specific alkaline phosphatase level higher than 26 μg/L was 12.7 months. Multivariate analysis indicated that higher serum C-terminal telopeptide of type I collagen independently increased the risk of death (hazard ratio 9.62; 95 % confidence interval 2.11-43.89; P = 0.003). Median overall survival for patients with serum C-terminal telopeptide of type I collagen level higher than 8.0 ng/ml was 31.1 months.. Baseline bone markers can be useful as predictors for disease progression and survival time in patients with bone metastasis from treatment-naïve prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Alkaline Phosphatase; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Biomarkers, Tumor; Bone Neoplasms; Diphosphonates; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Therapy, Combination; Follow-Up Studies; Goserelin; Humans; Imidazoles; Japan; Male; Middle Aged; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Risk Factors; Survival Rate; Time Factors; Tosyl Compounds; Zoledronic Acid

The efficacy of zoledronic acid in patients with treatment-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefits of combined zoledronic acid and androgen deprivation therapy in treatment-naïve prostate cancer with bone metastasis. The primary endpoint was skeletal-related event-free survival at 24 months.. Subjects were treatment-naïve patients with histologically confirmed adenocarcinoma of the prostate and radiological evidence of bone metastasis. Treatment consisted of bicalutamide 80 mg daily, goserelin acetate 10.8 mg every 12 weeks, and zoledronic acid 4 mg every 4 weeks. Zoledronic acid was continued for 24 months.. Of the patients enrolled between July 2008 and April 2010, 52 were included in the analyses. The median age of the patients was 72 years. The median baseline prostate-specific antigen level was 249.4 ng/mL. The median follow-up period was 33.3 months. The 24-month skeletal-related event-free survival rate was 84.4 % (95 % confidence interval 71.2-91.9). The median time to prostate-specific antigen progression was 25.9 months (95 % confidence interval 14.7-36.3). The median overall survival time was not reached. Improvement in pain or maintenance of no pain during the first 12 weeks was observed in 70 % of patients and the extent of bone disease was decreased in 10 % of patients at 12 months. Grade 3 osteonecrosis of the jaw was observed in three patients (5.8 %).. Zoledronic acid concomitant with androgen deprivation therapy as initial treatment in patients with treatment-naïve prostate cancer with bone metastasis resulted in an encouraging skeletal-related event-free survival rate at 24 months.

Topics: Aged; Androgen Antagonists; Androgens; Bone Neoplasms; Diphosphonates; Disease-Free Survival; Goserelin; Humans; Imidazoles; Male; Middle Aged; Neoplasm Staging; Prostate-Specific Antigen; Prostatic Neoplasms; Zoledronic Acid

This pilot study aimed to test the possibility of therapeutic benefit imparted by early intervention based on sequential tumour marker (TM) measurements during follow-up of primary breast cancer (PBC) patients.. Patients with oestrogen receptor positive PBC with no clinical and/or radiological evidence of metastases were recruited and followed-up 3-monthly with clinical assessment and TM (CA15.3 and CEA) measurements. The clinical team was blinded to the TM results. Asymptomatic patients who developed raised TMs (based on pre-defined cut-offs) were randomised to either 'treatment change' (either start or change of adjuvant endocrine agent to another agent) or 'no change' (control). Patients who developed symptomatic metastases came off the study. The primary and secondary endpoints were intervals from randomisation to symptomatic metastases and to last follow-up/death respectively.. Eighty-five patients (median age = 54 years (30-72)) were recruited with a median follow-up of 81 months (1-124). Sixteen patients were randomised as described. There was no significant difference (treatment change versus no change) with regards to interval from randomisation to symptomatic metastases - 23 (2-62) and 22 (1-63) months respectively (p = 0.9), as well as interval from randomisation to last follow-up/death - 36 (7-63) and 37 (10-63) months respectively (p = 0.9).. Despite long follow-up (up to 10+ years), this small study has thus far shown no significant difference in outcome. However, we have confirmed the feasibility of this study design but a larger study will be required to show if there is a benefit to this approach.

Topics: Adult; Aged; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Carcinoembryonic Antigen; Early Detection of Cancer; Female; Follow-Up Studies; Goserelin; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Mucin-1; Nitriles; Pilot Projects; Single-Blind Method; Tamoxifen; Treatment Outcome; Triazoles

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

The EORTC conducted two randomized phase III trials of maximal androgen blockade (MAB) in 695 patients with metastatic prostate cancer. Trial 30,843 compared orchidectomy or buserelin to buserelin plus cyproterone acetate and showed no significant difference in survival while trial 30,853 showed that Zoladex plus flutamide had a significantly longer survival than orchidectomy. Reasons for this discrepancy were sought.. In order to determine whether differences in patient characteristics could explain these possibly contradictory results, a Cox proportional hazards regression model was used to identify prognostic factors for survival in each study. Patients were divided into risk groups (good or poor prognosis with 3.5 and 1.75 years' median survival, respectively) based on their alkaline phosphatase, hemoglobin, performance status, pain score, T category and G grade at entry on study.. The survival advantage of MAB in 30,853 was limited to patients with a good prognosis (164/302 (54%) of the patients). In 30,843, only 93/337 patients (28%) had a good prognosis so there were insufficient data to draw separate conclusions in these patients. Despite the limitations of subgroup analyses, these results show that patients in 30,843 had on the average a worse prognosis than patients in 30,853. Hence there were fewer good prognosis patients who could potentially benefit from MAB, thus providing one possible explanation for the overall negative conclusion.. These studies once again underline the importance of taking into account patient characteristics when designing and interpreting metastatic prostate cancer trials. They also provide criteria which may be used to define risk groups as part of a protocol's patient eligibility criteria. In the design of future trials assessing MAB, a sufficient number of good prognosis patients should be entered to reliably assess treatment efficacy in this subgroup.

Topics: Aged; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Combined Modality Therapy; Cyproterone Acetate; Disease-Free Survival; Flutamide; Goserelin; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Orchiectomy; Prognosis; Proportional Hazards Models; Prostatic Neoplasms; Risk Assessment; Survival Rate

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

A prospective randomised study was performed to test the hypothesis that total androgen ablation, achieved by combining an LHRH analogue, goserelin acetate (Zoladex), with an antiandrogen, cyproterone acetate (Cyprostat), is more effective than conventional monotherapy in delaying the time to progression of metastatic prostatic cancer. 525 patients were recruited at 18 UK centres between May 1986 and January 1989, 175 patients being allocated to each arm. Patients were clinically and biochemically assessed at 1, 2, 3, 6, 9 and 12 months after initiation of therapy and then every 6 months until a maximum duration of 48 months. There was no statistically significant difference in terms of median time to progression between the combination treatment arm and either monotherapy arm, although there was a statistically significant difference between goserelin acetate alone and cyproterone acetate alone, in favour of goserelin acetate (p = 0.016). All treatment regimens were well tolerated and cyproterone acetate reduced both tumour flare reactions and hot flushes in patients receiving goserelin acetate. It is concluded that total androgen ablation using cyproterone acetate (300 mg/day) and goserelin acetate (3.6 mg every 28 days) confers no advantage in terms of time to progression, to conventional monotherapy, but can reduce certain side effects caused by LHRH analogue treatment alone.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyproterone Acetate; Disease Progression; Goserelin; Humans; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Safety

The use of goserelin with or without tamoxifen was investigated in a randomised multicentre study involving 318 pre- and perimenopausal advanced breast cancer patients. With a median follow-up of 93 weeks, 31% of goserelin-treated patients had objective responses (UICC criteria) compared with 38% of goserelin plus tamoxifen-treated patients (P = 0.24). There was a modest benefit in favour of combination therapy in time to progression (P = 0.03) but not in survival (P = 0.25). Median follow-up for survival was 117.5 weeks. Median times for disease progression and survival were 23 and 127 weeks in the goserelin alone group and 28 and 140 weeks in the combination group, respectively. In 115 patients with skeletal metastases only, significant differences in favour of combination therapy were seen in response rate, time to progression and survival. Both treatments were well tolerated and no additional safety issues were associated with combination therapy.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Female; Goserelin; Humans; Menopause; Middle Aged; Premenopause; Survival Rate; Tamoxifen; Time Factors; Treatment Outcome

This European Organization for Research and Treatment of Cancer (EORTC) trial 30853 is the fifth EORTC--Genitourinary Group randomized phase III trial of endocrine treatment for patients with newly diagnosed metastatic prostate cancer. Special attention was given to the assessment of response and/or progression. Each of the following factors was assessed separately as nonspecific and subjective criteria of response or progression: performance status, pain, alkaline and acid phosphatase, hemoglobin, urinary symptoms, and prostate-specific antigen (PSA). Objective progression was based on measurable disease. The observed sequence of progression was: (1) protein-specific antigen; (2) bone; (3) pain; and (4) performance status. Protein-specific antigen, an optional parameter, was the first sign of progression in more than 50% of patients whose disease had progressed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Flutamide; Goserelin; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Orchiectomy; Prospective Studies; Prostatic Neoplasms

Maximal androgen blockade (MAB), the eradication of the effects of adrenal androgens on prostate cancer cells after castration, has been used with differing success in the treatment of prostatic carcinoma. The aim of this randomized phase III study was to compare the efficacy and side effects of bilateral orchiectomy versus a combination of a luteinizing hormone-releasing hormone agonist (LHRH-A) depot formulation, goserelin acetate (3.6 mg s.c. once every four weeks), and flutamide (250 mg three times daily), in patients with metastatic cancer. Treatment usually continued until disease progression (or for a minimum of three months). Efficacy was assessed by response, time to disease progression, and duration of survival. Clinical evaluations, standard laboratory tests, and imaging examinations were carried out regularly. A total of 327 patients were entered in this study. There was a difference in response only for prostatic acid phosphatase (PAP) with a more frequent decrease of the serum values to normal in the serum in patients assigned to MAB treatment. The MAB treatment, however, proved significantly better for time to subjective progression, time to objective progression, time to first (subjective and objective) progression, and duration of survival. The most frequent side effects for both treatments included hot flushes and gynecomastia. In conclusion, significant time to progression and survival benefits are achieved by adding flutamide to an LHRH-A regimen, probably improving the quality of life of patients with metastatic cancer.

Topics: Aged; Bone Neoplasms; Combined Modality Therapy; Drug Therapy, Combination; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Prognosis; Prostatic Neoplasms; Survival Analysis

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

This article reviews the serial bone scans of 149 of 327 patients entered into a randomized prospective trial comparing orchidectomy versus zoladex and flutamide in patients with metastatic prostatic cancer. Attention is drawn to the difficulty of evaluating the response rate and of the importance of tumor load in determining survival. The use of sequential bone scans once the diagnosis of metastatic disease has been confirmed is of questionable value as the scans are expensive and contribute little to the further management of the patient in the absence of symptoms requiring relief.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Orchiectomy; Prostatic Neoplasms; Radionuclide Imaging; Randomized Controlled Trials as Topic; Survival Rate

A total of 327 patients with metastatic prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex depot supplemented by flutamide 250 mg 3 qid. Statistically significant increases in time to subjective and objective progression were recorded in favor of the combination treatment. No differences in time to death by cancer or overall death were recorded. The clinical significance of these differences will be reassessed once additional follow-up is available and further analysis of the overall clinical material has been carried out.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Flutamide; Goserelin; Humans; Male; Middle Aged; Multicenter Studies as Topic; Orchiectomy; Prognosis; Prostatic Neoplasms; Radionuclide Imaging; Randomized Controlled Trials as Topic; 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

Since March 1987, 304 evaluable patients with stage C and D prostate cancer have been entered into a prospective trial comparing Zoladex and Zoladex plus flutamide. To date, there has been no significant difference in over-all and progression-free survival between the 2 treatment groups. However, combined treatment produced a higher response rate (particularly in stage D patients) and a more rapid normalization of abnormal prostatic acid phosphatase levels. In addition, more prompt relief of bone pain was evident in the Zoladex plus flutamide group. However, significantly more side-effects were associated with combined treatment. These findings should be considered with caution because they form an interim analysis, and follow-up time is short. The results do suggest, however, that there is no particular advantage in using a combination of Zoladex plus flutamide compared to adding flutamide on failure of treatment with Zoladex alone.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Flutamide; Follow-Up Studies; Goserelin; Humans; Male; Neoplasm Staging; Prostatic Neoplasms; Survival Rate

A collaborative multicenter trial was conducted by 17 Italian groups to verify whether the so-called total androgen blockade obtained with luteinizing hormone releasing hormone (LHRH) analogs combined with antiandrogens is more effective than conventional monotherapy in the treatment of advanced prostatic cancer. A total of 328 previously untreated patients were evaluated: 163 patients received Zoladex depot alone, 3.6 mg subcutaneously every 28 days, and 165 patients received Zoladex depot plus cyproterone acetate (CPA), 200 mg/day orally. The follow-up period ranged from 41-251 weeks. Treatment was well tolerated, and side-effects in both groups mainly comprised loss of libido and erections, hot flashes and breast swelling and tenderness. There was no significant difference in objective response after 6, 12 and 24 months of treatment between the 2 groups. Median time to disease progression was comparable in both groups: 55 weeks in the Zoladex group and 54 weeks in the Zoladex plus CPA group. The time to disease progression and the survival distribution was comparable in both groups. Although there were no significant differences in the overall subjective response to both treatments, a faster improvement, with respect to pain and performance status was noted in the Zoladex plus CPA group (8 weeks) compared to Zoladex alone (12 weeks). The addition of antiandrogen, by inhibiting the initial elevation of plasma testosterone, may prevent the disease flare-up which occurs in a small number of patients during the first few days of treatment with LHRH analogs alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Phosphatase; Aged; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Buserelin; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms; Testosterone

In an open phase II, multicentre study with 118 pre- or perimenopausal women with histologically proven advanced breast cancer, Zoladex depot (3.6 mg) has been shown to produce an effective castration and response rates, which are comparable to those from oophorectomy.

Topics: Abdominal Neoplasms; Bone Neoplasms; Breast Neoplasms; Buserelin; Delayed-Action Preparations; Female; Goserelin; Humans; Multicenter Studies as Topic

One hundred and thirty-nine patients with advanced prostate cancer were entered into a randomised trial to test the efficacy and tolerance of goserelin 3.6 mg depot (Zoladex) versus stilboestrol 3 mg/day. As well as the usual clinical and radiological assessments of extent of disease, we used an immunoradiometric assay of prostate specific antigen (PSA) (Hybritech Europe) and normal laboratory enzymatic assays of acid phosphatase (AP) and alkaline phosphatase (ALKP) for biochemical assessment. The upper limit of normal for PSA was taken as 10 micrograms/l. The range of PSA was wide and differed significantly from that of AP and to a lesser extent ALKP in metastatic cases. PSA outperformed both AP and ALKP in both the local and advanced groups in terms of sensitivity. There was no correlation, however, between histological grade and level of PSA, AP or ALKP (the latter in cases with bone disease). In patients with metastatic disease diagnosed by bone scan, nine patients had one abnormal site/one "hot spot", and all of these had a PSA greater than twice the normal upper limit. Early death due to prostate cancer was noted in four patients with levels of PSA greater than 2500 micrograms/l. PSA is more sensitive than either enzymatic AP or ALKP in both locally advanced and metastatic prostate cancer and is useful in identifying those advanced cases who have single lesions on bone scan. In this series PSA gave an overall sensitivity of 89%, compared with 63% for AP and 64% for ALKP in patients with metastatic disease.

Topics: Acid Phosphatase; Alkaline Phosphatase; Antigens, Neoplasm; Biomarkers, Tumor; Bone Neoplasms; Buserelin; Diethylstilbestrol; Goserelin; Humans; Male; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms; Random Allocation

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Neoplasms; Estrogens; Flutamide; Goserelin; Humans; Male; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Time Factors; Treatment Outcome

Although there have been major improvements in the management of breast cancer, with a rapidly falling death rate despite an increasing incidence of the disease, metastatic breast cancer remains common and the cause of death in nearly 12 000 women annually in the UK. Numerous treatment options are available that either target the tumour or reduce the complications of the disease. Clinical decision making depends on knowledge of the extent and biology of the disease and available drug options, an understanding of the functional status, and also the wishes and expectations of the individual patient. In addition, the organisation of services and support of the patient are essential components of high-quality care. The National Institute for Health and Clinical Excellence (NICE) has produced guidelines for the treatment of advanced breast cancer, which in some areas have perhaps failed to appreciate the complexity of patient management. This guidance document aims to provide succinct practical advice on the treatment of metastatic breast cancer, highlight some limitations of the NICE guidelines, and provide suggestions for management where available data are limited.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Combined Modality Therapy; Decision Making; Female; Goserelin; Humans; Ovariectomy; Patient Care Team; Postmenopause; Premenopause; Radiotherapy; Tamoxifen; United Kingdom

Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. In the present study, we evaluated the oxidative status and antioxidant defense in patients with prostate cancer (PCa) taking into consideration: treatment, Gleason score and bone metastasis. For this, we measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasma and erythrocyte thiol levels and serum vitamin C and E concentration. This study was performed on 55 patients with PCa and 55 healthy men. TBARS levels and serum protein carbonylation were higher in PCa patients than in controls and altered levels of antioxidants were found in these patients. CAT activity was decreased and SOD activity was higher in PCa patients when compared with controls. Non-protein thiol levels were increased, however, serum vitamin C and vitamin E content were reduced in PCa patients when compared with controls. In addition, different parameters analyzed in PCa patients based on metastasis, treatment and Gleason score showed changes in oxidative stress biomarkers and antioxidant defenses. These findings may indicate an imbalance in the oxidant/antioxidant status, supporting the idea that oxidative stress plays a role in PCa, moreover, the oxidative profile appear to be modified by bone metastasis, treatment and Gleason score.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Ascorbic Acid; Bone Neoplasms; Catalase; Cyproterone Acetate; Erythrocytes; Goserelin; Humans; Lipid Peroxidation; Male; Middle Aged; Neoplasm Grading; Oxidative Stress; Prostatic Neoplasms; Protein Carbonylation; Sulfhydryl Compounds; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances; Vitamin E

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

Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Neoplasms; Breast Neoplasms; Capecitabine; Deoxycytidine; Female; Fluorouracil; Goserelin; Hematoma, Subdural, Intracranial; Humans; Indoles; Letrozole; Leukopenia; Nitriles; Pyrroles; Skull; Sunitinib; Triazoles

Prostate cancer (PCa) is the most commonly diagnosed cancer in American men with a subset inevitably presenting with metastatic disease to the bone. A well-recognized limitation in evaluating new treatments for metastatic PCa is the inability to use imaging to objectively assess response therapy. In this study, we evaluated the feasibility of clinically translating the functional diffusion map (fDM) imaging biomarker for quantifying the spatiotemporal effects of bone tumor response in a patient treated for metastatic PCa with bone metastases. A patient beginning therapy was scanned using MRI before treatment and again at 2 and 8 weeks post-treatment initiation to quantify changes in tumor diffusion values. Three metastatic lesions were identified for fDM analysis, all of which all demonstrated an early increase in diffusion values at 2 weeks, which increased further at 8 weeks post-treatment initiation. This finding correlated with a decrease in the patient's prostate-specific antigen (PSA) levels suggestive of patient response. CT, bone scans, and anatomic MRI images obtained posttreatment were found to be uninformative for the assessment of treatment effectiveness. This study presents the feasibility of fDM-measurements in osseous lesions over time and shows that changes in fDM values were consistent with therapeutic response. Thus, the fDM imaging biomarker may provide a quantifiable therapeutic endpoint to assess response in patients with metastatic bone cancer.

Topics: Adenocarcinoma; Aged; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Body Water; Bone Neoplasms; Cell Membrane Permeability; Diffusion Magnetic Resonance Imaging; Feasibility Studies; Goserelin; Humans; Male; Nitriles; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Tomography, X-Ray Computed; Tosyl Compounds; Treatment Outcome; Whole Body Imaging

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

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Neoplasms; Breast Neoplasms; Drug Resistance, Neoplasm; Female; Goserelin; Humans; Liver Neoplasms; Neoplasm Recurrence, Local; Premenopause

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

To study the role of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in monitoring the response of bone metastases to endocrine therapy combined with bisphosphonates in patients with breast cancer.. Ten breast cancer patients with bone metastases who were to receive endocrine therapy and bisphosphonates were investigated prospectively by DCE-MRI. We chose a reference lesion for each patient who was studied at baseline, within 3 weeks from the second administration of bisphosphonates, and after 4 and 8 months from the initiation of medical treatment. Time/intensity curves, representing temporal changes of signal intensity in areas of interest in the context of the target lesions (ROI), were obtained for each DCE-MRI.. Changes in the shape of the T/I curves suggesting tumor regression were seen shortly after the initiation of medical treatment in the three patients who had the most durable responses.. DCE-MRI has the potential to detect early changes related to medical treatment in bone metastases from breast cancer. If confirmed in larger series, these data identify DCE-MRI as a diagnostic tool for evaluating new bone targeting antineoplastic agents.

Topics: Adult; Aged; Anastrozole; Bone Neoplasms; Breast Neoplasms; Diphosphonates; Female; Goserelin; Humans; Imidazoles; Letrozole; Magnetic Resonance Imaging; Middle Aged; Nitriles; Pamidronate; Pilot Projects; Prospective Studies; Tamoxifen; Triazoles; Zoledronic Acid

In the present study, we investigated the diagnostic effectiveness of biochemical markers of bone turnover for the detection of bone metastasis from prostate cancer and changes in the levels of these markers caused by hormonal therapy. Ninety-five patients with prostate cancer were divided into one of three groups: 26 patients with bone metastasis (BM(+)), 35 patients without bone metastasis on nonhormonal therapy (BM(-)HT(-)) and 34 patients without bone metastasis on hormonal therapy (BM(-)HT(+)). All patients in the BM(+) group had received hormonal therapy. Serum or urinary levels of the following biochemical markers of bone turnover were examined: bone-specific alkaline phosphatase (B-ALP), osteocalcin (OC), type I procoIlagen C-propeptide (PICP), type I collagen cross-linked C-telopeptide (ICTP), C-telopeptide fragment (CTx), N-telopeptide fragment (NTx), total pyridinoline (T-Pyr), total deoxypyridinoline (T-D-Pyr) and free deoxypyridinoline (F-D-Pyr). The BM(+) group showed significantly higher values than the BM(-)HT(-) group for B-ALP, PICP, NTx, CTx, T-Pyr, T-D-Pyr, and F-D-Pyr. Compared with the BM(-)HT(+) group, the BM(-) group showed significantly higher values for B-ALP, ICTP, NTx, T-Pyr and T-D-Pyr. The levels of B-ALP, NTx, CTx, T-D-Pyr and F-D-Pyr were significantly different between the BM(-)HT(-) and BM(-)HT(+) groups. All markers, except OC and CTx, significantly were correlated with the extent of bone metastasis on bone scintigraphy. Of all markers, receiver operating characteristic (ROC) analyses revealed B-ALP and F-D-Pyr to be the most sensitive and specific for differentiation between the BM(+) and BM(-)HT(-) groups with regard to bone formation and resorption. respectively. In contrast, B-ALP and ICTP were most sensitive and specific for differentiation between the BM(+) and BM(-)HT(+) groups. The results suggest that hormonal therapy greatly affects the efficacy of PICP, CTx and F-D-Pyr in the diagnosis of bone metastasis, whereas its effects on ICTP are small. Although bone metabolic markers would be useful in the diagnosis of bone metastasis from prostate cancer, the effects of hormonal therapy on bone metabolism should be kept in mind in their evaluation.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Bone Resorption; Flutamide; Goserelin; Humans; Male; Osteogenesis; Prostatic Neoplasms; Radionuclide Imaging; ROC Curve

Topics: Antineoplastic Agents, Hormonal; Bone Neoplasms; Goserelin; Humans; Male; Middle Aged; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Testosterone

Topics: Adenocarcinoma; Antineoplastic Agents, Hormonal; Bone Neoplasms; Goserelin; Humans; Male; Middle Aged; Orchiectomy; Palliative Care; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Failure

A 44-year-old premenopausal woman having local recurrence and pleural and bone metastases of breast cancer was treated with aromatization inhibition in combination with Luteinizing Hormone-releasing Hormone (LH-RH) agonist. The dominant site of metastasis was a painful local lesion invading the chest wall. A partial response by reducing the size of the local lesion was attained 3 months after initiation of treatment. This result suggested that treatment using aromatization inhibition in combination with LH-RH agonist would be effective in premenopausal breast cancer. To confirm the effectiveness of this treatment, comparative study between aromatization inhibition in combination with LH-RH agonist aromatization inhibition alone and anti-estrogen in combination with LH-RH agonist are needed.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Bone Neoplasms; Breast Neoplasms; Enzyme Inhibitors; Fadrozole; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Neoplasm Recurrence, Local; Pleural Neoplasms; Premenopause

The aim of this study was to investigate the effect of goserelin-acetat (Zoladex) on testosterone suppression, to compare achieved suppression with clinical effects in patients with prostate cancer with bone metastases and consequent painful syndrome, to study the behavior of adiol during treatment and to assess life quality with emphases on the physical and psychological domain in relation to clinical and biological treatment effects. Fifteen patients were treated by Zoladex in one dose every 28 days, and followed-up for 12 months. All patients had several metastatic localizations in the bones, initial high prostate specific antigen (PSA), and high acid (AP) and alkaline phosphatase (ALP). PSA, testosterone, adiol (delta-5-androstenediol), luteinizing hormone (LH), foliculostimulating hormone (FSH), ALP and AP were also measured before every cycle. For evaluation of the life quality Rotterdam Symptom Checklist was used. Clinical progression was not registered during follow-up, with drop of PSA, ALP and AP. Testosterone and adiol displayed mainly inverse trends during treatment. The complete testosterone suppression was never achieved. It seems that Zoladex has quite different influence on LH and FSH, as levels of those hormones have shown opposite trend. Some of the observed hormonal effects could be attributed to stimulation of the monoamine system. Suppression of LH level provoked by administration of LHRH agonists increases level of dopamine in hypothalamus which inhibits releasing of its hormones. By inhibition of corticotropic releasing factor and ACTH, and by its influence on adrenal gland, we could explain drop of adiol levels in the first months of administration of LHRH agonists. Testosterone increase and adiol drop in the first months, and adiol increase following testosterone level drop in the fourth to eight month, may be explained by negative feed back mechanism between different androgens which could be stimulated or provoked by LHRH therapy. The question of effects which are results of LHRH agonists modulation of the monoamine system and consequent activation of other central mechanisms of hormonal regulation is still open. Patients' quality of life under therapy was improved for about 30% in psychological and functional domains. There were no significant changes on physical subscale, during treatment. It seems that the obtained positive psychological treatment effect is not only a consequence of pain decrease, but it could be the result o

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Alkaline Phosphatase; Androstenediol; Antineoplastic Agents, Hormonal; Bone Neoplasms; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Testosterone

A 44-year-old premenopausal woman with bone metastases of breast cancer was initially treated with systemic chemotherapy (CEF) and radiation therapy after standard mastectomy. However, progressive change of bone metastases with elevation of tumor markers (CEA, NCC-ST 439) was detected, so continuous administration of LH-RH agonist and combination chemotherapy (CEF) were conducted. Subsequently, complete objective regression was attained after 40 weeks.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Neoplasms; Breast Neoplasms; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Remission Induction

Eighty-two patients with advanced prostatic carcinoma were treated with a long-acting luteinizing hormone releasing hormone (LHRH) agonist (Zoladex depot, Zeneca Pharmaceuticals, England). The outcome of the treatment was monitored on the basis of the following prognostic factors: local stage, number of bone metastases, histological differentiation grade and prostate-specific acid phosphatase (PAP), alkaline phosphatase (AF) and testosterone levels. The patients were followed-up until disease progression or until death. The mean weight of the prostate decreased from 48.1 g to 17.4 g (P < 0.00001) during the first year of treatment. Statistically there was a significant difference in regard to appearance of progression between different clinical stages (P < 0.00001). The prognosis was poorest in patients with more than 10 metastases at the primary stage. If the PAP level was initially higher (over 20 micrograms/L), the prognosis was very poor. Statistically there was a significant difference between the high PAP level and the slightly elevated or normal PAP (P < 0.02 and P < 0.005, respectively). Alkaline phosphatase (AF) appeared to be a good prognostic factor. The prognosis was particularly poor, if the AF level exceeded 1000 U/L (P < 0.00001 and P < 0.05, compared with normal AP and slightly elevated AP level, respectively). Surprisingly, a high pre-treatment testosterone level worsened the prognosis during the LHRH agonist treatment (P < 0.01, compared to patients with normal testosterone level). This is a new finding and controversial to the findings reported before.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Follow-Up Studies; Goserelin; Humans; Life Tables; Male; Neoplasm Staging; Prognosis; Prostate; Prostatic Neoplasms; Testosterone; Time Factors; Treatment Outcome

Two patients with prostate carcinoma and bone metastases were treated with hormonal therapy. Radioimmune imaging of bone marrow performed with 99mTc-labeled antigranulocyte antibody BW 250/183 before treatment demonstrated absence of granulopoietic bone marrow in extensive regions of the central and proximal peripheral skeleton, indicating diffuse bone marrow invasion. Bone marrow scans performed after treatment demonstrated presence of granulopoietic bone marrow in these regions, indicating bone marrow regeneration. This finding was consistent with favorable response to treatment.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Bone Marrow; Bone Neoplasms; Buserelin; Flutamide; Goserelin; Humans; Male; Middle Aged; Organotechnetium Compounds; Prostatic Neoplasms; Radionuclide Imaging; Regeneration

Serum prostate-specific antigen (PSA) levels were studied in the EORTC trial of zoladex plus flutamide versus orchidectomy in metastatic prostatic cancer. Forty-four of 60 patients had a decrease of PSA to less than or equal to 10 ng/ml at 3 to 6 months after treatment. The combination of a PSA less than 10 ng/ml after 3 to 6 months treatment and less than 15 spots on the bone scintigram at entry gave the highest probability of not having progressed by 24 months. A rising PSA anticipated bone progression by 6 to 12 months in 13 of 28 patients (46%). The PSA at entry to the trial was related to survival; a discriminant of 300 ng/ml distinguished a poor and better risk group. The lowest level of PSA reached during the first 6 months of treatment was also a univariate survival factor.

Topics: Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Buserelin; Flutamide; Goserelin; Humans; Male; Orchiectomy; Predictive Value of Tests; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radionuclide Imaging; Survival Rate

A series of tumour related markers have been examined in 179 patients receiving primary endocrine therapy for metastatic breast cancer. Significant correlations between therapeutic response (UICC criteria after 6 months of treatment) and appropriate alterations in serum concentrations of carcinoembryonic antigen, ferritin, c-reactive protein, orosomucoid and the erythrocyte sedimentation rate, have been observed when changes in these markers were examined only at high serum concentrations. By combining these five markers a 'therapeutic index' of response has been devised which can be employed at an early stage of treatment in more than 90% of patients, giving an overall sensitivity/specificity of 90%/78% for therapeutic response or disease stabilisation over a 6-month period. The design of an objective measurement of response, which is easy to perform, has the potential to replace the existing, largely subjective. UICC criteria for retrospective judgement of response, and may also be used to direct systemic endocrine therapy.

Topics: Biomarkers, Tumor; Blood Sedimentation; Bone Neoplasms; Breast Neoplasms; Buserelin; C-Reactive Protein; Carcinoembryonic Antigen; Female; Ferritins; Goserelin; Humans; Lung Neoplasms; Megestrol; Megestrol Acetate; Orosomucoid; Ovariectomy; Tamoxifen

Ferritin concentrations have been measured in serum from 266 patients receiving primary endocrine therapy for advanced breast cancer. Concentrations were significantly higher at presentation of advanced disease than in 55 tumour-free control patients. A positive correlation existed between increasing serum ferritin and tumour burden at presentation. A strong correlation was also found between therapeutic response and changes in serum ferritin (above 200 micrograms/l) in patients with distant metastases. More than one third of patients presenting with Stage IV disease developed concentrations in excess of 200 micrograms/l during initial treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Buserelin; Female; Ferritins; Follow-Up Studies; Goserelin; Humans; Lung Neoplasms; Megestrol; Megestrol Acetate; Middle Aged; Neoplasm Staging; Ovariectomy; Remission Induction; Retrospective Studies; Tamoxifen

Ovarian granulosa cell tumor lung metastases regressed, and symptoms were relieved, during gonadotropin-releasing hormone (GnRH) agonist analog therapy after the failure of operative treatment and cytotoxic chemotherapy, indicating the hormone dependence of the malignancy. The response was transient, but the largest metastasis did not relapse. This case report suggests that GnRH analogs may offer a new approach to the treatment of ovarian stromal cell malignancies.

Topics: Bone Neoplasms; Buserelin; Female; Goserelin; Granulosa Cell Tumor; Humans; Lung Neoplasms; Middle Aged; Ovarian Neoplasms; Pituitary Hormone-Releasing Hormones

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

Topics: Bone Neoplasms; Breast Neoplasms; Buserelin; Female; Goserelin; Humans; Lung Neoplasms; Middle Aged

The clinical and endocrine response to a depot preparation of the LH-RH analogue ICI 118630 (Zoladex) was assessed in 55 untreated patients with advanced prostatic cancer. Whereas gonadal androgen suppression was achieved in all patients, subjective and objective clinical response occurred in only 69%, indicated by a relief of bone pain, a decrease in the size of the primary tumour and lymph node metastases and improvement in bone scan appearances. A third of these patients, however, subsequently showed progression of their disease. Serious side effects were not encountered in this study. The depot formulation is a simple, safe and convenient method of administering Zoladex and offers an alternative treatment for metastatic prostatic cancer.

Topics: Acid Phosphatase; Aged; Alkaline Phosphatase; Bone Neoplasms; Buserelin; Delayed-Action Preparations; Goserelin; Humans; Luteinizing Hormone; Lymphatic Metastasis; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Random Allocation; Testosterone

Ten previously untreated postmenopausal women with metastatic breast cancer, none of whom had received prior systemic therapy, were treated with the luteinising hormone releasing hormone (LHRH) analogue D-Ser(But)6, Azgly10-LHRH (ICI 118630). Two obtained an objective partial remission, one in bone metastases and one in lung metastases. One patient proved unassessable. Amongst the seven failures, incomplete pituitary gonadotrophin suppression over the relatively short treatment period with the daily injections was noted. The seven patients failing ICI 118630 received tamoxifen and two with high tumour oestrogen receptor values responded. LHRH analogues may provide a novel endocrine therapy for postmenopausal breast cancer although more data are needed. In this study, the monthly depot injection proved superior to daily injections with regard to gonadotrophin suppression, although it is not clear that this provides the mechanism of action.

Topics: Adult; Aged; Bone Neoplasms; Breast Neoplasms; Buserelin; Female; Follicle Stimulating Hormone; Goserelin; Humans; Lung Neoplasms; Luteinizing Hormone; Menopause; Middle Aged; Remission Induction

Seventeen patients with advanced progressive prostatic cancer who had relapsed or failed to respond to conventional endocrine therapy with oestrogens, orchiectomy or antiandrogens were treated with the LHRH analogue, ICI 118630. No significant objective tumour responses were seen, though 11 of 15 patients who presented with symptomatic metastatic bone pain had rapid short-term pain relief. The lack of objective clinical response seen in this study indicates no justification for the use of LHRH analogues in this group of patients. Though a significant subjective response was seen there was no added advantage over regular analgesics.

Topics: Acid Phosphatase; Alkaline Phosphatase; Analgesia; Bone Neoplasms; Buserelin; Goserelin; Hormones; Humans; Male; Prostatic Neoplasms

9 of 12 patients with advanced metastatic carcinoma of the prostate treated with luteinising-hormone-releasing-hormone (LHRH) analogue ICI 118630 for a mean period of 6 months showed objective evidence of response to treatment. Of 8 patients with bone pain, 7 obtained relief. After 6 weeks of treatment testosterone concentrations were reduced to castrate levels (range less than 2 to 5.5 nmol/l) from a pretreatment mean value of 15.7 nmol/l (range 10.3-24 nmol/l). Basal gonadotropin levels and gonadotropin responses to acute LHRH stimulation were suppressed within 2 weeks of treatment. However, the testosterone response to stimulation with human chorionic gonadotropin was unimpaired 4 weeks after the start of treatment. Therefore suppression of the basal testosterone concentration by ICI 118630 was due to inhibition of pituitary luteinising-hormone secretion rather than direct inhibition of testicular Leydig-cell function. ICI 118630 offers an alternative treatment to orchidectomy and oestrogen therapy.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Chorionic Gonadotropin; Depression, Chemical; Gonadotropin-Releasing Hormone; Goserelin; Humans; Lymphatic Metastasis; Male; Middle Aged; Pain; Pelvis; Prostatic Neoplasms; Radiography; Testosterone