goserelin and Neoplasm-Metastasis

The choice of endocrine therapy for breast cancer depends on the menopausal status and stage of disease. Endocrine therapy remains the first choice and most important component in the treatment of hormone sensitive non-life threatening advanced breast cancer. In premenopausal women with metastatic disease, the combination of a luteinizing hormone-releasing hormone (LH-RH) agonist plus tamoxifen is reasonable as first-line endocrine therapy. In postmenopausal patients with recurrent disease progressing after or during adjuvant tamoxifen, third-generation aromatase inhibitors (AIs) are the preferred first-line endocrine treatment. Many premenopausal and postmenopausal women with hormone responsive breast cancer benefit from sequential use of endocrine therapies at the time of disease progression. Recent clinical trials designs have been implemented, employing AIs as monotherapy in postmenopausal breast cancer patients, as first-line adjuvant therapy, and in sequence either 2-3 or 5 years, with initial tamoxifen. Emerging results from these trials indicate an advantage to patients for any of these strategies, and most international guidelines now suggest the use of an AI in the adjuvant setting in postmenopausal women. The use of endocrine treatment for metastatic and early breast cancer will be reviewed here.

Topics: Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Breast Neoplasms; Gonadotropin-Releasing Hormone; Goserelin; Neoplasm Metastasis; Neoplasm Staging; Postmenopause; Premenopause; Tamoxifen

Endocrine therapy is usually indicated prior to chemotherapy as the first line therapy for metastatic breast cancer patients because of its milder toxicity. Patients who respond to a first-line endocrine therapy have a high chance of responding to a second-line endocrine therapy, and thus the responders to a first-line endocrine therapy would better be treated with second or third-line endocrine therapy. In the adjuvant setting, tamoxifen (antiestrogen) has been proven to improve the prognosis of both pre- and postmenopausal estrogen receptor positive breast cancer patients, and goserelin (LH-RH agonist) has been proven to improve prognosis in premenopausal women comparable to chemotherapy (CMF). Very recently, preliminary results have indicated that anastrozole (aromatase inhibitor) is superior to tamoxifen as adjuvant treatment for estrogen receptor positive postmenopausal breast cancer patients. In addition, the recent success of tamoxifen in a chemoprevention trial seems to have ushered in a new era wherein prevention of breast cancer is much more emphasized than treatment of established breast cancer.

Topics: Algorithms; Anastrozole; Antineoplastic Agents, Hormonal; Breast Neoplasms; Chemoprevention; Chemotherapy, Adjuvant; Climacteric; Female; Goserelin; Humans; Neoplasm Metastasis; Nitriles; Tamoxifen; Triazoles

The logic behind the application of luteinizing hormone-releasing hormone (LHRH) agonists in combination with tamoxifen in premenopausal women is that LHRH agonists on the one hand suppress the tamoxifen-induced stimulation of the pituitary-ovarian function and, on the other hand, seem as effective as surgical castration. This meta-analysis combines all randomized evidence to compare the combined treatment with LHRH agonist alone with respect to overall survival, progression-free survival, and objective response in premenopausal women with advanced breast cancer.. Four clinical trials randomizing a total of 506 premenopausal women with advanced breast cancer to LHRH agonist alone or to the combined treatment of LHRH agonist plus tamoxifen were identified. Meta-analytic techniques were used to analyze individual patient data from these trials.. With a median follow-up of 6.8 years, there was a significant survival benefit (stratified log-rank test, P = .02; hazards ratio [HR] = 0.78) and progression-free survival benefit (stratified log-rank test, P = .0003; HR = 0.70) in favor of the combined treatment. The overall response rate was significantly higher on combined endocrine treatment (stratified Mantel Haenszel test, P = .03; odds ratio = 0.67).. The combination of LHRH agonist plus tamoxifen is superior to LHRH agonist alone in premenopausal women with advanced breast cancer. Therefore, if a premenopausal woman with advanced breast cancer is thought to be suitable for endocrine treatment, it is proposed that the combination of a LHRH agonist plus tamoxifen be considered as the new standard treatment.

Topics: Antineoplastic Agents, Hormonal; Breast Neoplasms; Buserelin; Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Goserelin; Humans; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Premenopause; Randomized Controlled Trials as Topic; Survival Analysis; Tamoxifen

We investigated the efficacy and safety of fulvestrant plus goserelin (F + G) versus anastrozole plus goserelin (A + G) in comparison with goserelin (G) alone in premenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), tamoxifen-pretreated metastatic breast cancer (MBC).. In this multicentre, open-label, randomised phase II study, premenopausal women aged ≥18 years with HR+, HER2-, tamoxifen-pretreated MBC were randomly assigned (1:1:1) to F + G, A + G or G alone. The primary end-point was time to progression (TTP). Secondary end-points included overall survival, overall response rate, clinical benefit rate and toxicity.. Of 138 eligible patients, 44 were randomly assigned to receive F + G, 47 to A + G and 47 to G alone. The median follow-up duration was 32.2 months (interquartile range: 23.69-40.86) and the median age was 43.0 years (range 23.0-55.0). The median TTP was 16.3 months (95% confidence interval [CI] 7.5-25.1) for F + G, 14.5 months (95% CI 11.0-18.0) for A + G and 13.5 months (95% CI 10.3-16.8) for G alone. Compared with G alone, the hazard ratios were 0.608 for F + G (95% CI, 0.370-0.998; p = 0.049) and 0.982 for A + G (95% CI, 0.624-1.546; p = 0.937). In terms of visceral metastasis, a stratification factor, there were no TTP differences according to treatment arm. Grade III or IV toxicities were rarely observed. Of the common adverse events, grade I arthralgia and joint stiffness were more frequently observed in the F + G than in the A + G or G-alone groups (p < 0.05, respectively).. F + G provides a promising new option for the treatment of premenopausal women with HR+, HER2-, tamoxifen-pretreated MBC.. ClinicalTrials.gov number NCT01266213 and Korean Cancer Study Group (KCSG) Breast cancer protocol number BR10-04.

Topics: Adult; Anastrozole; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Fulvestrant; Goserelin; Humans; Neoplasm Metastasis; Premenopause; Tamoxifen

The aim of the study was to compare intermittent (IAD) and continuous (CAD) androgen deprivation therapy (ADT) between locally advanced (M0) and metastatic (M1) prostate cancer, and the effect of ADT on the quality of life.. In total, 852 men with advanced prostate cancer were enrolled to receive goserelin acetate for 24 weeks. Of these, 554 patients whose prostate-specific antigen (PSA) decreased to less than 10 ng/ml or by at least 50% (<20 ng/ml at baseline) were randomized to IAD or CAD. In the IAD arm, ADT was resumed for at least 24 weeks whenever PSA increased to greater than 20 ng/ml or above baseline.. Median follow-up time was 65 months. Median times from randomization to progression, death, prostate cancer death and treatment failure in M0 and M1 patients were 46.8 and 21.4, 57.6 and 40.3, 59.5 and 40.7, and 41.9 and 20.0 months, respectively (p < 0.001). No significant differences emerged between IAD and CAD. ADT showed a beneficial effect on pain, activity limitation and social functioning in M1 patients, and a deleterious effect on physical capacity in M0 patients and on sexual functioning in both groups. IAD offered extra benefit for activity limitation, social functioning and recovery of sexual functioning.. IAD is as efficient as CAD in treatment of locally advanced and metastatic prostate cancer. ADT improves quality of life in M1 patients, with IAD offering extra benefit.

Topics: Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Disease Progression; Disease-Free Survival; Follow-Up Studies; Goserelin; Health Status; Humans; Male; Neoplasm Metastasis; Pain Measurement; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Sexuality; Social Participation; Survival Rate; Time Factors

Castration resistance occurs in most patients with metastatic hormone-sensitive prostate cancer who are receiving androgen-deprivation therapy. Replacing androgens before progression of the disease is hypothesized to prolong androgen dependence.. Men with newly diagnosed, metastatic, hormone-sensitive prostate cancer, a performance status of 0 to 2, and a prostate-specific antigen (PSA) level of 5 ng per milliliter or higher received a luteinizing hormone-releasing hormone analogue and an antiandrogen agent for 7 months. We then randomly assigned patients in whom the PSA level fell to 4 ng per milliliter or lower to continuous or intermittent androgen deprivation, with patients stratified according to prior or no prior hormonal therapy, performance status, and extent of disease (minimal or extensive). The coprimary objectives were to assess whether intermittent therapy was noninferior to continuous therapy with respect to survival, with a one-sided test with an upper boundary of the hazard ratio of 1.20, and whether quality of life differed between the groups 3 months after randomization.. A total of 3040 patients were enrolled, of whom 1535 were included in the analysis: 765 randomly assigned to continuous androgen deprivation and 770 assigned to intermittent androgen deprivation. The median follow-up period was 9.8 years. Median survival was 5.8 years in the continuous-therapy group and 5.1 years in the intermittent-therapy group (hazard ratio for death with intermittent therapy, 1.10; 90% confidence interval, 0.99 to 1.23). Intermittent therapy was associated with better erectile function and mental health (P<0.001 and P=0.003, respectively) at month 3 but not thereafter. There were no significant differences between the groups in the number of treatment-related high-grade adverse events.. Our findings were statistically inconclusive. In patients with metastatic hormone-sensitive prostate cancer, the confidence interval for survival exceeded the upper boundary for noninferiority, suggesting that we cannot rule out a 20% greater risk of death with intermittent therapy than with continuous therapy, but too few events occurred to rule out significant inferiority of intermittent therapy. Intermittent therapy resulted in small improvements in quality of life. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00002651.).

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Confidence Intervals; Drug Administration Schedule; Follow-Up Studies; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Middle Aged; Neoplasm Metastasis; Nitriles; Penile Erection; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Survival Analysis; Tosyl Compounds

Endocrine therapy is the preferred treatment for hormone-receptor (HR) positive metastatic breast cancer. In premenopausal patients, ovarian function suppression with goserelin in combination with anastrozole yielded promising results in phase II studies. Fulvestrant, a pure antioestrogen, yields high rates of disease stabilisation in postmenopausal women. Therefore, we investigated the feasibility and safety of fulvestrant plus goserelin in premenopausal women with HR-positive metastatic breast cancer.. Premenopausal patients with metastatic breast cancer eligible for endocrine treatment received fulvestrant 250 mg and goserelin 3.6 mg every four weeks as first- to fourth-line therapy. Clinical benefit rate (CBR; response rate plus disease stabilisation ≥ 6 months) was defined as the primary study end-point. Time to progression (TTP) and overall survival (OS) were estimated using the Kaplan-Meier product limit method.. Twenty-six patients received treatment as scheduled. 81% were pre-treated with tamoxifen and 69% had received prior aromatase inhibitors in combination with goserelin. The majority of patients (69%) presented with visceral metastases. Complete response was observed in a single patient, partial response in three and disease stabilisation ≥ 6 months in eleven patients, resulting in a CBR of 58%. Median TTP was 6 months (95%confidence interval (CI), 2.4-9.6) and OS 32 months (95%CI, 14.28-49.72), respectively.. Results suggest that the combination of fulvestrant and goserelin offers promising activity in premenopausal patients and further investigation is warranted.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estradiol; Estrogen Antagonists; Female; Fulvestrant; Goserelin; Humans; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Premenopause

To report our long-term follow-up of an institutional randomized prospective trial of radical prostatectomy (RP) with or without a 3-month course of neoadjuvant hormone therapy (NHT), which results in pathological downstaging, but generally no reduction in biochemical recurrence (BCR) on early follow-up (at 3 years).. From December 1992 to June 1996, 148 patients with clinically localized prostate cancer were randomized to RP only or 3 months of goserelin acetate and flutamide before RP. BCR was defined as a detectable serum prostate specific antigen level (>0.1 ng/mL) at least 6 weeks after surgery, with a confirmatory increase.. The median follow-up for BCR-free patients was 8 years. There was no significant difference in BCR-free probabilities between groups (P = 0.7). The BCR-free probability at 7 years was 78% for patients undergoing RP only and 80% for patients undergoing NHT and RP (difference of 2%; 95% confidence interval, CI, 12-16%). A Cox regression showed no significant relationship between NHT and BCR (hazard ratio 1.16; 95% CI, 0.56-2.39, P = 0.7). Overall, two patients had local recurrence and six developed metastases, and were evenly distributed among the RP only and NHT groups.. Although our study was not originally powered to detect differences in BCR, there was no overall benefit in BCR-free probability, local recurrence or metastasis with 3 months of NHT at 8 years of follow-up. Pending evidence of improvement in patient outcomes, NHT before RP appears to be unjustified outside of clinical trials.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Epidemiologic Methods; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prostatectomy; Prostatic Neoplasms; Treatment Outcome

Goserelin and letrozole in premenopausal patients can result in clinical outcomes comparable to those obtained by letrozole alone in postmenopausal patients with metastatic breast cancer (MBC).. A total of 73 patients with hormone-responsive MBC were included. Of those, 35 premenopausal patients received goserelin (3.6 mg subcutaneously every 28 days) plus letrozole (2.5 mg orally daily), and 38 postmenopausal patients received letrozole alone as their first-line endocrine therapy in a metastatic setting.. Baseline characteristics were similar in the two groups, except for a younger age (median, 41 v 53.5 years; P < .001) and a shorter disease-free interval (median, 1.8 v 3.3 years; P = .03) in the premenopausal group. Clinical benefit rates were comparable between the two groups (77% v 74%; P = .77). With the median follow-up of 27.4 months, there was no statistical difference in the median time to progression between the two groups (9.5 months [95% CI, 6.4 to 12.1 months] v 8.9 months [95% CI, 6.4 to 13.3 months]). In patients who did not receive bisphosphonate, letrozole +/- goserelin caused a greater loss of bone mineral density at 6 months compared with that of patients receiving bisphosphonate treatment (premenopausal group, -16.7% v 53.9%; P = .002 and postmenopausal group, -13.3% v 17.4%; P = .04 at the lumbar spine).. Clinical efficacies in premenopausal MBC patients with combined letrozole and goserelin therapy were comparable to those in postmenopausal patients treated with letrozole alone. Although letrozole +/- goserelin resulted in a modest increase in bone resorption, concurrent treatment with bisphosphonate could prevent bone loss at 6 months.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Biopsy, Needle; Bone Density; Breast Neoplasms; Disease Progression; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Goserelin; Humans; Immunohistochemistry; Injections, Subcutaneous; Kaplan-Meier Estimate; Letrozole; Maximum Tolerated Dose; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Staging; Nitriles; Postmenopause; Premenopause; Probability; Prognosis; Proportional Hazards Models; Risk Assessment; Statistics, Nonparametric; Survival Analysis; Treatment Outcome; Triazoles

To explore the antitumor activity of the aromatase inhibitor, anastrozole, in the treatment of premenopausal women with hormone receptor-positive, metastatic breast cancer who have been rendered functionally postmenopausal with the use of the luteinizing hormone-releasing hormone agonist, goserelin.. Premenopausal women with estrogen and/or progesterone receptor-positive, metastatic or recurrent breast cancer were enrolled in this prospective, single-arm, multicenter phase II trial. Patients were treated with goserelin 3.6 mg subcutaneous monthly and began anastrozole 1-mg daily 21 days after the first injection of goserelin. Patients continued on treatment until disease progression or unacceptable toxicity.. Thirty-five patients were enrolled of which 32 were evaluable for response and toxicity. Estradiol suppression was assessed, with mean estradiol levels of 18.7 pg/mL at 3 months and 14.8 pg/mL at 6 months. One participant (3.1%) experienced a complete response, 11 (34.4%) experienced partial response, and 11 (34.4%) experienced stable disease for 6 months or longer for a clinical benefit rate of 71.9%. Median time to progression was 8.3 months (range, 2.1 to 63+) and median survival was not been reached (range, 11.1 to 63+). The most common adverse events were fatigue (50%), arthralgias (53%), and hot flashes (59%). There were no grade 4 to 5 toxicities.. The combination of goserelin plus anastrozole has substantial antitumor activity in the treatment of premenopausal women with hormone receptor-positive metastatic breast cancer.

Topics: Adult; Anastrozole; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Estradiol; Female; Goserelin; Humans; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Nitriles; Premenopause; Triazoles

Prostatectomy or radiation for localized prostate cancer (PC) can fail in up to 15% to 30% of patients. The purpose of this study was to determine feasibility, tolerability, and outcome of docetaxel followed by hormone therapy in men experiencing an increasing prostate-specific antigen (PSA) after their primary local treatments for PC.. Men with increasing serum PSA after prostatectomy or/and radiation were eligible. Serum PSA had to be > or = 4 ng/mL and serum testosterone had to be in the noncastrate range. Treatment included docetaxel 70 mg/m2 every 3 weeks for up to six cycles, followed by total androgen suppression (luteinizing hormone-releasing hormone agonist plus bicalutamide) and peripheral androgen blockade (finasteride plus bicalutamide) for 12 to 20 months.. Thirty-nine men were enrolled; 32 had PSA-only failure, seven also had clinical metastasis. Baseline median PSA was 13.7 ng/mL. Serum PSA decreased > or = 50% in 17 of 35 patients (48.5%) and > or = 75% in seven of 35 patients (20%) with docetaxel. The PSA decreased to a median of 0.1 ng/mL with subsequent hormone therapy. In 28 of 33 patients the PSA increased (median, 0.41 ng/mL) at a median follow-up of 2.3 months after treatment. In contrast, in five of 33 men the PSA remains at 0.1 ng/mL at a median of 18.9 months after therapy; three of these five men had soft tissue metastasis at entry but remain in complete remission. The most common grade 3 to 4 toxicity was neutropenia (61.5%).. Docetaxel followed by hormone therapy of limited duration may provide disease control in subgroups of men experiencing failure after local treatments for PC.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Docetaxel; Goserelin; Humans; Infusions, Intravenous; Injections, Intramuscular; Injections, Subcutaneous; Leuprolide; Male; Middle Aged; Neoplasm Metastasis; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Taxoids; Treatment Outcome

DNA ploidy has consistently been found to be a correlate of prostate cancer patient outcome. However, a minority of studies have used pretreatment diagnostic material and have involved radiotherapy (RT)-treated patients. In this retrospective study, the predictive value of DNA ploidy was evaluated in patients entered into Radiation Therapy Oncology Group protocol 8610. The protocol treatment randomization was RT alone versus RT plus short-course (approximately 4 months) neoadjuvant and concurrent total androgen blockade (RT+TAB).. The study population consisted of 149 patients, of whom 74 received RT alone and 75 received RT+TAB. DNA content was determined by image analysis of Feulgen stained tissue sections; 94 patients were diploid and 55 patients were nondiploid. Kaplan-Meier univariate survival, the cumulative incidence method, and Cox proportional hazards multivariate analyses were used to evaluate the relationship of DNA ploidy to distant metastasis and overall survival.. DNA nondiploidy was not associated with any of the other prognostic factors in univariate analyses. In Kaplan-Meier analyses, 5-year overall survival was 70% for those with diploid tumors and 42% for nondiploid tumors. Cox proportional hazards regression revealed that nondiploidy was independently associated with reduced overall survival. No correlation was observed between DNA ploidy and distant metastasis. The diminished survival in the absence of an increase in distant metastasis was related to a reduction in the effect of salvage androgen ablation; patients treated initially with RT+TAB and who had nondiploid tumors had reduced survival after salvage androgen ablation.. Nondiploidy was associated with shorter survival, which seemed to be related to reduced response to salvage hormone therapy for those previously exposed to short-term TAB.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Combined Modality Therapy; Diploidy; DNA, Neoplasm; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Proportional Hazards Models; Prostatic Neoplasms; Retrospective Studies; Salvage Therapy; Survival Rate

This Gynecologic Oncology Group (GOG) study was designed to estimate the activity of goserelin acetate as treatment for advanced and recurrent endometrial carcinoma. Forty evaluable patients received monthly treatment with goserelin acetate at a dose of 3.6 mg, given subcutaneously. Standard GOG response and adverse effects criteria were used. The median age of patients was 71 years. Seventy-one percent of patients had received prior radiation therapy; 18% of patients were reported to have received prior progestational therapy for endometrial cancer. One patient had received prior chemotherapy. There were two complete responses (5%) and three partial responses (7%). One response occurred in a patient who previously did not respond to progestin therapy after having achieved a response. The overall response rate was 11% (95% CI: 4-27%). Median progression-free survival was 1.9 months and median overall survival was 7.3 months. No severe or life-threatening toxicities occurred because of goserelin. Deep venous thrombosis developed in two patients. This study confirmed the limited activity of goserelin acetate in endometrial carcinoma, with only one response in a patient previously treated with hormonal therapy. The activity is insufficient to warrant further study of the single agent at this time. Elucidation of the mechanism of action of this drug may allow more effective use in conjunction with other agents in the future.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Endometrial Neoplasms; Female; Goserelin; Humans; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Survival Analysis

We wanted to determine whether neoadjuvant systemic chemoendocrine therapy guided by the estrogen receptor (ER) status of the primary breast cancer, followed by conventional surgery and/or radiotherapy, reduces local and distant recurrence and improves survival compared with adjuvant treatment given conventionally postoperatively.. Two hundred ten patients with primary breast cancer (T1-T4, N0, N1-2) were randomised to receive treatment with neoadjuvant chemoendocrine therapy or conventional post-operative chemoendocrine therapy. Systemic therapy was based on the estrogen receptor (ER) status of the primary tumour obtained by trucut core biopsy. ER-negative patients received MMM chemotherapy (methotrexate (30 mg/m2), mitozantrone (7 mg/m2) and mitomycin (7 mg/m2) three-weekly for three months and ER-positive patients who were premenopausal received goserelin (3.75 mg monthly), and post menopausal women formestane (250 mg every two weeks) over three months.. With a minimum of five years follow-up, there is no evidence of any survival benefit from the pretreatment neoadjuvant therapy regimen, with five year overall survival being 79% +/- 4.7% (neoadjuvant) and 87% +/- 3.4% (adjuvant). Similarly, there was no apparent benefit in terms of disease-free survival. There was, however, a significant reduction in the incidence of distant metastases in responders (4 of 51; 8%) compared with non-responders (17 of 49; 35%) (P < 0.01). There was a reduction in the need for surgery in responding patients with T1 and T2 tumours, since 10 of 74 (14%) had no detectable residual tumour, without any apparent increase in the risk of local or distant recurrence.. In this study neoadjuvant treatment with endocrine or chemotherapy provided no obvious survival benefit to women with breast cancer. However, it does allow avoidance of surgery in some cases. Also, the patients whose tumours respond to neoadjuvant systemic therapy have a lower incidence of distant metastases after five year follow-up compared to those whose tumours fail to respond.

Topics: Adult; Aged; Androstenedione; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Goserelin; Humans; Methotrexate; Middle Aged; Mitomycin; Mitoxantrone; Neoadjuvant Therapy; Neoplasm Metastasis; Postmenopause; Premenopause; Prognosis; Receptors, Estrogen; Survival Analysis

The first data analysis of the European Organization for Research and Treatment of Cancer (EORTC) 30853 trial indicated a significantly longer time to progression and duration of survival for the maximal androgen blockade (MAB) treatment arm. However, the MAB treatment arm had a higher frequency of reported side effects.. The quality-adjusted survival (Q-TWiST) method was applied to perform a secondary analysis of the EORTC 30853 trial in order to obtain a quality-adjusted survival (QAS) analysis. Two models with different definitions of the progression health state were used for the analysis. In the first model, progression was defined by both objective and subjective criteria, and in the second model only by increase in pain score. The approach was also extended to include an analysis using actual utility scores (Q-tility) of patients in the relevant health states.. Based on Q-tility scores obtained from a separate study of a cohort of prostate cancer patients, the QAS analysis resulted in a 5.2-month difference (95% CI, -1.1; 11.5 months) in favor of zoladex and flutamide, equal in magnitude to the benefit found in the unadjusted survival analysis.. A QAS analysis such as the Q-TWiST method may be preferred over the unadjusted approach in clinical trials where the health states are clearly distinct, and differ significantly in either duration or quality of life (QOL), or both. The second model, with progression defined as increase in pain score, made no difference to the results in this study because of the small difference in duration of the pain-progression health state between treatment arms. However, Q-tility scores from the separate cross-sectional study that was used in this Q-TWiST analysis showed that a subjective definition of health states better reflects differences in QOL between the health states that the patients experience during follow-up.

Topics: Antineoplastic Agents, Hormonal; Combined Modality Therapy; Flutamide; Goserelin; Humans; Male; Neoplasm Metastasis; Orchiectomy; Pain Measurement; Prostatic Neoplasms; Quality of Life; Quality-Adjusted Life Years; Survival Analysis

To compare failure-free survival (FFS) and overall survival (OS) for patients with metastatic breast cancer treated with the gonadotropin-releasing hormone (GN-RH) agonist, goserelin versus surgical ovariectomy.. Between August 1, 1987 and July 15, 1995 138 (136 eligible) premenopausal patients with estrogen receptor (ER)- and/or progesterone receptor (PgR)-positive metastatic breast cancer were entered by the Southwest Oncology Group (SWOG), North Central Cancer Treatment Group (NCCTG), and Eastern Cooperative Oncology Group (ECOG). Prior chemotherapy or hormone therapy for metastatic disease was not allowed. Patients were randomly assigned to goserelin (3.6 mg subcutaneously every 4 weeks; (n = 69) versus surgical ovariectomy (n = 67). The study was initially designed as an equivalence trial with 80% power to rule out a 50% improvement in survival due to ovariectomy. However, accrual was slow and the study was terminated early, which resulted in a final power of 60% for the alternative hypothesis of equal survival distributions.. FFS and OS were similar for goserelin and ovariectomy. The goserelin/ovariectomy death hazards ratio was .80 and the associated 95% confidence interval (CI) was .53 to 1.20. The test of 50% improvement in survival due to ovariectomy was rejected at P = .006. Goserelin lowered serum estradiol to postmenopausal levels. Hot flashes (75% v 46%) and tumor flare (16% v 3%) were more common with goserelin.. Goserelin and ovariectomy resulted in similar FFS and OS. We can rule out a moderate advantage for ovariectomy. Goserelin was safe and well tolerated.

Topics: Adult; Antineoplastic Agents, Hormonal; Breast Neoplasms; Disease-Free Survival; Female; Goserelin; Humans; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Ovariectomy; Premenopause; Receptors, Estrogen; Receptors, Progesterone

To review the outcome of therapy with maximal androgen blockade and compare the efficacy and safety of bicalutamide and flutamide, each used in combination with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with untreated metastatic (Stage D2) prostate cancer.. Randomized, double-blind (for antiandrogen therapy), multicenter study with a 2 x 2 factorial design. A total of 813 patients were allocated 1:1 to bicalutamide (50 mg once daily) or flutamide (250 mg three times daily), plus 2:1 to goserelin acetate (3.6 mg every 28 days) or leuprolide acetate (7.5 mg every 28 days).. At the time of analysis (median follow-up, 49 weeks), bicalutamide plus LHRH-A was associated with a statistically significant improvement in time-to-treatment failure, the primary endpoint, when compared with flutamide plus LHRH-A. The results with longer follow-up (median, 95 weeks) support previous findings of an improved time-to-treatment failure with bicalutamide plus LHRH-A; however, the difference between groups was not statistically significant. A treatment failure endpoint was reached by 68% of patients in the bicalutamide plus LHRH-A group, compared with 72% of patients in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.87 (95% confidence interval [CI], 0.74-1.03; P = 0.10). The upper one-sided 95% confidence limit for survival was 1.00, meeting the definition for equivalence (< 1.25). With longer follow-up, overall mortality was 34%, with equivalent survival between groups: 32% of patients in the bicalutamide plus LHRH-A group died, compared with 35% in the flutamide plus LHRH-A group. The hazard ratio of bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.88 (95% CI, 0.69-1.11; P = 0.29). The upper one-sided 95% confidence limit for survival was 1.07, meeting the definition for equivalence (< 1.25). Diarrhea occurred in 24% of patients in the flutamide plus LHRH-A group compared with 10% of patients in the bicalutamide plus LHRH-A group (P < 0.001).. In patients with metastatic prostate cancer, bicalutamide plus LHRH-A is effective and well tolerated. Because of its efficacy and tolerability profile, together with its convenient once-daily dosing formulation, bicalutamide represents a prime candidate for antiandrogen of first choice in combination with LHRH-A therapy in the treatment of men with metastatic prostate cancer.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Double-Blind Method; Flutamide; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Metastasis; Nitriles; Prostatic Neoplasms; Tosyl Compounds

To test the feasibility of using intermittent androgen suppression in the treatment of prostate cancer by taking advantage of the reversible action of medical castration.. Observations were made on a group of 47 patients (clinical Stage D2, 14; D1, 10; C, 19; B2, 2; and A2, 2) with a mean follow-up time of 125 weeks. Treatment was initiated with combined androgen blockade and continued for at least 6 months until a serum prostate-specific antigen (PSA) nadir was observed. Medication was then withheld until the serum PSA increased to a mean value between 10 and 20 ng/mL. This cycle of treatment and no treatment was repeated until the regulation of serum PSA became androgen independent.. The first two treatment cycles lasted 73 and 75 weeks, with a mean time off therapy of 30 and 33 weeks and an overall mean percentage time off therapy of 41% and 45%, respectively. The mean time to achieve a nadir level of serum PSA was 20 weeks in cycle 1 and 18 weeks in cycle 2. Serum testosterone returned to the normal range within 8 weeks (range, 1 to 26) of stopping treatment. The off-treatment period in both cycles was associated with an improvement in sense of well-being and the recovery of libido and potency in the men who reported normal or near-normal sexual function before the start of therapy. In 7 patients with Stage D2 disease, the cancer progressed to an androgen-independent state. The mean and median times to progression were 128 weeks and 108 weeks, respectively. Seven patients have died, 1 from a noncancer-related illness, with mean and median overall survival times of 210 weeks and 166 weeks, respectively.. Prostate cancer is amenable to control by intermittent androgen suppression. This approach affords an improved quality of life when the patient is off therapy. It also results in reduced toxicity and cost of treatment and possibly delays tumor progression. Whether survival is affected in a beneficial or adverse way remains to be studied in a randomized, prospective study.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Cyproterone Acetate; Diethylstilbestrol; Drug Therapy, Combination; Follow-Up Studies; Goserelin; Humans; Leuprolide; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Neoplasms, Hormone-Dependent; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Rate; Time Factors

To determine the response rate of postmenopausal breast cancer patients to the gonadotropin-releasing hormone (GN-RH) agonist, Zoladex (goserelin; ICI Pharma, Wilmington, DE).. A multi-institutional single-agent trial in postmenopausal patients was conducted. Serum levels of follicle-stimulating hormone (FSH), testosterone, and estradiol were requested before and after Zoladex treatment.. For estrogen receptor-positive (ER+) patients, the response rate was 11%, with one complete response (CR) and three partial responses (PRs) among 36 eligible patients. Responses were of short duration. There were no responses among 16 estrogen receptor-negative (ER-) patients.. GN-RH agonists have activity in ER+ postmenopausal patients, but response rates are not as high as with other available endocrine therapies and the duration of response is short.

Topics: Aged; Breast Neoplasms; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Goserelin; Humans; Menopause; Middle Aged; Neoplasm Metastasis; Receptors, Estrogen; Survival Analysis; Treatment Outcome

Zoladex plus flutamide significantly delays the time to progression (subjective, objective, first progression) compared with orchiectomy, but no difference in survival (death from all causes or from malignant disease) could be detected. Thus, a delay in the appearance of progression has not improved survival. In fact, the duration of survival after progression tends to be shorter on Zoladex plus flutamide. There is thus no evidence to suggest any survival benefit with Zoladex plus flutamide. The quality control of our data revealed acknowledged problems in defining responses in patients with advanced prostate cancer. The review of the Bone Scan Committee provided the data for Tables 5 to 7. These data must provoke some reflections and emphasize once again the heterogeneity of the studied patient population. Table 4 on pain response after 4 weeks is just one of the many items to be analyzed by the committees for response criteria and quality of life. We expect that the other trials face similar problems. More work and patience are needed to obtain a firm answer to this clinical problem. These efforts will never be wasted, however, because the combined results of these trials will increase our knowledge of the treated history of prostate cancer and will, we hope, indicate a net treatment benefit in some subsets of patients. An individually tailored treatment for each patient selected from the anonymous mass of cases of advanced prostate cancer would be the highest reward of our continued collaboration with all the study groups.

Topics: Aged; Buserelin; Flutamide; Goserelin; Humans; Male; Middle Aged; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms

Continuous administration of gonadotrophin-releasing hormone (GnRH-)analogues leads to a receptor-down regulation of pituitary GnRH-receptors and subsequently inhibits ovarian hormone production. Since October, 1984, 118 evaluable pre- and perimenopausal patients (median age 42, range 25-55 years) with metastatic breast cancer were entered into an open phase II multicenter trial to evaluate efficacy of this new treatment modality. Patients were treated with the GnRH-analogue Goserelin (3.6 mg depot s.c. every 4 weeks) as first line therapy and followed up until progression. Mean serum gonadotrophins LH and FSH were significantly suppressed by Goserelin. Within 2-3 weeks, mean serum E2 values decreased to values seen in castrated women (less than 30 pg/ml). Overall objective response with complete and partial remissions (CR + PR) was achieved in 44.9% of patients with a median time to progression (mTTP) of 59 weeks, (range 20-163 weeks), no change (NC) in 28.0% with a mTPP of 27 weeks (range 16-101 weeks), and progression (P) in 27.1%. Responses were seen in ER-positive as well as ER-negative tumors, and in patients with different sites of metastases (locoregional, bone, visceral, multiple). The value of different prognostic factors in relation to response rates, time to progression and time to death (overall survival) is discussed. Median overall survival (time from beginning of palliative Goserelin treatment to death) was 148 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Breast Neoplasms; Buserelin; Combined Modality Therapy; Delayed-Action Preparations; Drug Evaluation; Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Middle Aged; Neoplasm Metastasis

One hundred thirty-four pre- and perimenopausal patients presenting with metastatic breast cancer (median age, 42 years; range, 25 to 55) were treated with goserelin (Zoladex [ICI 118 630]; ICI Pharma, Plankstadt, Germany) a long-acting gonadotrophin-releasing hormone (GnRH)-analogue depot formulation, injected subcutaneously every 4 weeks, as a first-line therapy. One hundred eighteen patients were evaluable for response. Serum concentrations of estradiol, luteinizing hormones (LH), and follicle-stimulating hormones were significantly suppressed by Zoladex. Mean serum estradiol values fell into the range of castrated or postmenopausal women within 2 to 3 weeks of therapy. This suppression was maintained for the duration of therapy. Overall objective response was: 12 (10.2%) complete remission; 41 (34.7%) partial remission; 33 (28.0%) no change; and 32 (27.1%) progression. In responders, the median time to response was 4 months (range, 2 to 11 months), median duration of response was 8 + months (range 2 to 24 months), and median time to progression was 11 + months (range, 5 to 30 months). Objective responses were seen for different sites of metastases: loco-regional (62.5%), bone (46.7%), visceral (45.0%), and multiple (35.1%). Tumor remission was more common in patients in which the primary tumor was estrogen receptor (ER)-positive (49.3%) or ER-unknown (44.0%), but appreciable response rates were also observed in ER-poor patients (33.3%). Zoladex depot was well tolerated both locally and systemically. It produced effective castration and the objective response rates and duration of remission are at least comparable to those seen following oophorectomy; however, the side effects are less. The use of depot Zoladex avoids the psychological trauma and operative morbidity of the irreversible operative castration.

Topics: Adult; Breast Neoplasms; Buserelin; Delayed-Action Preparations; Female; Goserelin; Humans; Injections, Subcutaneous; Menopause; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Receptors, Estrogen; Receptors, Progesterone; Remission Induction

From April 1984 to May 1986, 129 patients with prostate cancer entered a prospective trial with a new LH-RH agonist, Zoladex. Mean age was 72 years (range of 45-94 years) and, in most cases, patients had metastatic disease, not previously treated by chemotherapy or hormone therapy. Patients received a monthly injection of 3.6 mg. Serum testosterone was lowered into the range of castrate levels after 4 weeks of treatment. In 105 evaluable patients at 3 months, a 65% partial response (PR) rate was observed, with 11% stable and 24% progressive disease. Median time to progression was 37 weeks. Analysis of objective criteria revealed 30% PR for prostate volume and 51% CR-PR for prostatic acid phosphatases. Seventeen percent of lytic metastases had recalcified. One hundred twenty-nine patients were evaluable for toxicity. Endocrinological side effects were common: decrease in libido, 92%; impotence, 86%; hot flushes, 48%; and breast swelling or tenderness, 9%. Nonendocrinologic side effects were rare. The treatment is generally well accepted by patients owing to the convenient depot formulation and to the minor side effects.

Topics: Acid Phosphatase; Aged; Aged, 80 and over; Buserelin; Delayed-Action Preparations; Follicle Stimulating Hormone; France; Goserelin; Humans; Injections, Subcutaneous; Luteinizing Hormone; Male; Middle Aged; Multicenter Studies as Topic; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prospective Studies; Prostate; Prostatic Neoplasms

A randomized, controlled trial of the treatment of metastatic prostatic cancer using either the LH-RH analogue Zoladex or orchidectomy is reported. The trial was conducted in the U.K. and Ireland and involved participants in 17 centers. The design of the trial is outlined and the response criteria discussed. The results show that the patient characteristics in the two treatment groups were comparable upon entry. Repeated administration of Zoladex every 28 days has been shown to be as effective as orchidectomy in lowering serum testosterone to castrate levels. The subjective and objective response rates were similar, as were the duration of response, time to treatment failure, and survival rates. The withdrawals from the trial and adverse reactions are discussed. These results, 10 months after the closure of recruitment to the trial, seem to indicate that Zoladex and orchidectomy are equivalent treatments and that Zoladex seems to be a truly medical alternative to surgical castration. Finally, other ongoing U.K. trials of the treatment of advanced prostate cancer are outlined.

Topics: Aged; Buserelin; Clinical Trials as Topic; Delayed-Action Preparations; Goserelin; Humans; Injections, Subcutaneous; Male; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms; Remission Induction; Testosterone; United Kingdom

A study comparing Zoladex 3.6 mg depot with diethylstilbestrol (DES) 3 mg/day was initiated in August 1985. One hundred ninety-three patients with histologically confirmed prostate cancer T3/4 or M1 have been randomized up to 31 March 1987: 95 to Zoladex, 98 to DES. No patient had received prior systemic therapy. There is no bias in the treatment groups in terms of baseline characteristics. Median follow-up is 11 months, and the response rate at 12 months from randomization (CR + PR) for Zoladex is 70 +/- 9.4% and 50 +/- 10.1% for DES. Median time to best response is 6 months for Zoladex and 12 months for DES (using the Kaplan-Meier life table method). Subjective responses are 56 +/- 10.2% for Zoladex and 44 +/- 10% for DES. Five increases in bone pain were found after the first Zoladex treatment, as well as one increased ureteric obstruction. None required treatment withdrawal. Seventeen patients on DES were withdrawn due to adverse reaction (chi 2 = 4.33, 1df, p less than 0.05). Overall survival at 31 March 1987 is 84% for the Zoladex group and 78% for the DES group. This study has shown that Zoladex is superior to DES in achieving early tumor response in advanced prostate cancer, without causing serious complications warranting withdrawal of treatment.

Topics: Buserelin; Delayed-Action Preparations; Diethylstilbestrol; England; Follow-Up Studies; Goserelin; Humans; Male; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Random Allocation; Remission Induction; Testosterone

Data regarding the safety and effectiveness of aromatase inhibitors (AIs) as monotherapy or combined with gonadotropin-releasing hormone (GnRH) analogue in male breast cancer are scarce.. In this retrospective chart review, cases of male breast cancer patients treated with AIs with or without a GnRH analogue were evaluated.. Twenty-three men were included into this case series. Aromatase inhibitors in combination with or without a GnRH analogue were given as first-line therapy in 60.9% and as second-line therapy in 39.1% of patients, respectively. All patients had visceral metastases, whereas in five of them bone lesions coexisted. In all cases AIs were tolerated well, and no case of grade 3 and 4 adverse events was reported. A partial response was observed in 26.1% of patients and stable disease in 56.5%. Median overall survival (OS) was 39 months and median progression-free survival (PFS) was 13 months. Regarding OS and PFS, no significant effects of GnRH analogue co-administration or type of AI were noted.. Our study shows that AIs with or without GnRH analogues may represent an effective and safe treatment option for hormone-receptor positive, pretreated, metastatic, male breast cancer patients.

Topics: Aged; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Breast Neoplasms, Male; Gonadotropin-Releasing Hormone; Goserelin; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Retrospective Studies

To develop a Risk Score (RS) to predict distant recurrence among premenopausal women with node-negative endocrine-responsive early breast cancer.. The Cox model was used to develop the RS using clinical and histopathological features from 378 women participating in the IBCSG Trial VIII who received endocrine therapy alone or following chemotherapy. The performance of the resulting model was validated on a cohort of 1005 patients from a single institution who received endocrine therapy alone.. In a multivariable analysis, the risk of distant recurrence was associated with tumor size, ER, Ki-67 and peritumoral vascular invasion. In the validation cohort, patients with high RS were at greater risk of distant recurrence compared to patients with low RS (HR, 17.41; 95% CI, 5.72-52.95).. In premenopausal women with node-negative endocrine-responsive early breast cancer, the RS identifies patients at higher risk of distant recurrence.

Topics: Adult; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Decision Support Techniques; Female; Fluorouracil; Goserelin; Humans; Ki-67 Antigen; Methotrexate; Middle Aged; Multivariate Analysis; Neoplasm Invasiveness; Neoplasm Metastasis; Nomograms; Premenopause; Randomized Controlled Trials as Topic; Receptors, Estrogen; Risk Assessment; Survival Analysis; Tamoxifen; Treatment Outcome; Tumor Burden

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

Haemoglobin levels often decline into the anaemic range with androgen deprivation therapy (ADT). We conducted a chart review of patients receiving ADT for metastatic prostate cancer to assess anaemia-related symptoms.. 135 stage IV prostate cancer cases were reviewed for treatment type; haemoglobin values before and after treatment; and symptoms of anaemia. Mean haemoglobin levels before and after for all treatment forms, for leuprolide alone, and for combination leuprolide/bicalutamide were calculated and evaluated for significant differences. The numbers of patients developing symptoms were recorded and the effects of specific therapies evaluated.. For all ADT treated patients, mean haemoglobin declined by -1.11 g/dL (p<.0001). Leuprolide-alone treated patients had a mean decline of -1.66 g/dL (p<0.0001). Leuprolide and bicalutamide combination treatment caused a mean decline of -0.78 g/dL (p=0.0426). 16 of 43 patients had anemia symptoms. Contingency analysis with Fisher's exact test shows patients receiving leuprolide therapy alone versus other forms of ADT were significantly less likely to have symptoms (chi(2)=0.0190).. The present study confirms that ADT results in a significant drop in haemoglobin levels into the anaemic range. A number of patients become symptomatic from this change. Practitioners should monitor haemoglobin levels, and treat symptomatic patients.

Topics: Aged; Androgen Antagonists; Anemia; Anilides; Antineoplastic Agents, Hormonal; Combined Modality Therapy; Goserelin; Hemoglobins; Humans; Leuprolide; Linear Models; Male; Neoplasm Metastasis; Nitriles; Prostatic Neoplasms; Retrospective Studies; Tosyl Compounds

The changes in serum prostate specific antigen (PSA) concentrations can be used as a prognostic factor in patients undergoing maximum androgen blockade for metastatic prostate cancer.. A total of 149 patients followed up in our department were classified into 4 groups on the basis of PSA changes: group 1; those with normalisation of PSA levels within the first 3 months, group 2; those with normalisation PSA between months 3 and 6, group 3; those with a decrease in PSA but not reaching normal range, group 4; those with no decrease. The gleason scores and the number of bone metastases were also compared between the groups.. The time to progression was significantly delayed in group 1 (mean: 23.3 months) compared to those with group 2 (mean: 16.9 months) (P<0.02). The time to progression in group 3 (mean: 8.45 months) was significantly shorter compared to the first two groups (P<0.001). Also, in patients with gleason scores 5-7 (grades 2) and gleason scores over 7 (grade 3) and group 1, the time to progression (mean: 21.2 months) was significantly delayed compared to those with the same gleason scores but with group 2 (mean: 13.4 months) (P<0.001).. The decrease in PSA level is more important than gleason scores in determining the time to progression. Early normalisation of PSA delays the time to progression, and when combined with gleason scores, PSA is an important prognostic factor in predicting the success of the therapy.

Topics: Aged; Antineoplastic Agents, Hormonal; Goserelin; Humans; Leuprolide; Male; Middle Aged; Monitoring, Physiologic; Neoplasm Metastasis; Orchiectomy; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies

Several oncogenes and tumour-suppressor genes have been identified that may have an important role in the development of human breast carcinoma. Furthermore, some of these gene alterations may be linked to the development of invasion and subsequent metastasis. Alterations in the expression of ras p21, p53 and c-erbB-2 have all been linked to tumours with rapid cellular proliferation, but the evidence that they are of prognostic importance in patients with breast cancer is conflicting. This study explores the relationship between expression of these oncoproteins and clinical outcome in 92 patients with either locally advanced or metastatic breast cancer treated with primary endocrine therapy. Specimens of the primary carcinoma were available for analysis of hormone receptor, Ki67 labelling index, epidermal growth factor receptor (EGFR), c-erbB-2, p53 and ras p21. Clinical response was measured according to UICC criteria after 6 months of treatment and all patients were followed for time to progression and overall survival. As shown previously, oestrogen receptor (ER) negativity, high Ki67 labelling index and EGFR overexpression were associated with a shorter time to progression and overall survival. However, no statistically significant relationship existed between expression of ras p21, p53 or c-erbB-2 and response to treatment, time to progression or overall survival. We conclude that staining for these three oncoproteins has no role in therapeutic decision-making in patients with advanced breast cancer. The negative finding implies that while abnormal expression of these genes may have an important role in the development of breast cancer, the variations in growth characteristics of advanced breast cancer may be influenced by other factors.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Breast Neoplasms; ErbB Receptors; Estrogen Antagonists; Female; Gene Expression Regulation, Neoplastic; Goserelin; Humans; Ki-67 Antigen; Life Tables; Megestrol; Megestrol Acetate; Menopause; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasm Proteins; Nuclear Proteins; Proportional Hazards Models; Proto-Oncogene Proteins p21(ras); Receptor, ErbB-2; Receptors, Estrogen; Tamoxifen; Treatment Outcome; Tumor Suppressor Protein p53

A 78-year-old male was treated with goserelin (Zoladex) for 16 months for metastasizing prostate carcinoma. This therapy is clinically equivalent to orchidectomy, as the application of the luteinizing hormone-releasing hormone (LHRH)-analogue Zoladex causes suppression of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by down-regulation of pituitary receptors. Consequently, testicular androgen production is inhibited and testosterone levels are decreased to castration levels. In the present case we found diffuse, partially nodular hyperplasia of growth hormone (GH) and adrenocorticotropin (ACTH) producing cells in the anterior pituitary gland at autopsy. As Zoladex reduces pituitary receptors for releasing hormones (RH), a globally increased hypothalamic secretion of RH might be responsible for the ACTH- and the GH-cell hyperplasia. We cannot exclude that Zoladex may cause not only adenomas in rat pituitary glands as reported previously, but also a (nodular) hyperplasia of the pituitary gland in man.

Topics: Adrenocorticotropic Hormone; Aged; Buserelin; Goserelin; Growth Hormone; Humans; Hyperplasia; Immunohistochemistry; Male; Neoplasm Metastasis; Orchiectomy; Pituitary Gland, Anterior; Prostatic Neoplasms

The toxicity and side effects of combination therapy with zoladex and flutamide have not been excessive compared with those due to orchidectomy. Pain due to the flare phenomenon has not been observed with zoladex and flutamide. Treatment modification has been necessary in 12 of the 149 patients receiving the combination therapy, compared with one of 148 patients who had surgical castration. Only one patient had flutamide withdrawn because of diarrhea and only five patients had treatment modification because of liver toxicity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Buserelin; Flutamide; Goserelin; Humans; Male; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms

Medical castration obtained with luteinizing hormone releasing hormone (LHRH) analogues in patients with prostate cancer is now well established. To block the initial stimulation of testosterone production and prevent the risk of the so-called flare-up with this medication, we investigated short-term combination therapy with 1 mg of diethylstilbestrol (DES). Fourteen previously untreated patients with histologically proved metastatic prostatic carcinoma were treated with 1 mg DES po daily one week prior to the initiation of therapy with LHRH analogues depot injection of Zoladex (ICI 116630) and continued during four weeks after the first depot injection. LHRH depot form was maintained as long as patients experienced clinical benefit. Endocrinologic results show that in spite of 1 mg of DES a significant increase of testosterone is still observed in the first week after injection of the LHRH depot form. Hence, this combination is not useful to prevent endocrinologic and clinical flare-up in patients with prostate cancer treated with LHRH analogues.

Topics: Aged; Buserelin; Diethylstilbestrol; Drug Evaluation; Drug Therapy, Combination; Goserelin; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Testosterone

Medicinal castration using GnRH-analogues is a new therapeutic possibility for treating metastasizing breast cancer in premenopausal women. A total of 22 premenopausal patients were included in the study reported here, all of them low-risk cases. Twenty of the 22 patients had hormone receptor-positive primary tumors. A slow-release depot form of Zoladex (ICI 118630) was used as a GnRH agonist and was administered subcutaneously (3.6 mg) at four-week intervals. The long-term administration of Zoladex brought about a significant reduction in blood FSH, estradiol, and progesterone levels within one to four weeks. In contrast, there were no detectable changes in ACTH, DHEAS, cortisol, testosterone, prolactin, or androstendion levels. Therapy-induced amenorrhea occurred in all cases. The objective remission rate achieved (complete and partial remission) was 45%. As opposed to other formulations, the use of Zoladex as a GnRH analog in depot form has significant advantages, which become particularly evident through improved compliance. With Zoladex therapy an effective drug-induced castration can be accomplished in premenopausal women. As regards its efficacy it is comparable to an ovarectomy, though with less pronounced side effects.

Topics: Adult; Breast Neoplasms; Buserelin; Female; Follow-Up Studies; Gonadal Steroid Hormones; Goserelin; Humans; Injections, Subcutaneous; Middle Aged; Neoplasm Metastasis

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

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