goserelin and Cardiovascular-Diseases

Androgen deprivation therapy (ADT) is associated with coronary heart disease and diabetes in men with prostate cancer (PCa); however, controversy exists regarding ADT and cardiovascular mortality (CVM) with limited data for lower risk disease.. We conducted a hypothesis-generating retrospective analysis to evaluate the relationship between short-course ADT and CVM in patients with clinically localized PCa enrolled in a phase III trial.. A total of 1979 men with clinically localized (T1b-2b, prostate-specific antigen [PSA] <20 ng/ml) PCa enrolled in Radiation Therapy Oncology Group (RTOG) 94-08 from 1994 to 2001. Patients were randomized to radiation therapy (RT) with or without short-course ADT (4 mo of gonadotropin-releasing hormone (GnRH) agonist therapy and antiandrogen). Median follow-up was 9.1 yr for survivors.. The Cox proportional hazards model assessed overall survival. The Fine-Gray proportional hazards model assessed disease-specific survival (DSS) and CVM. Covariates included age, race, weight, baseline cardiovascular disease, baseline diabetes, baseline hypertension, Gleason score, T stage, and PSA.. Short-course ADT improved overall survival and DSS and was not associated with an increased risk of CVM. Overall, 191 cardiovascular-related deaths were observed. At 10 yr, 83 patients (cumulative incidence rate: 10%) receiving RT and ADT versus 95 patients (cumulative incidence rate: 11%) receiving RT alone experienced CVM. The treatment arm was not associated with increased CVM (unadjusted hazard ratio: 1.07; confidence interval, 0.81-1.42; p=0.62). Increased CVM was not observed in patients at low risk of PCa death or at high risk of cardiac-related death.. Data from patients enrolled in RTOG 94-08 support the hypothesis that ADT does not increase CVM risk in men with clinically localized PCa treated with short-course GnRH agonist therapy. These data support ADT use in settings with proven survival benefit.. We investigated the controversial relationship between hormone therapy and cardiovascular mortality in men with prostate cancer (PCa) treated with radiation in a large randomized trial. Our data suggest that hormone therapy does not increase the risk of cardiovascular death in patients with clinically localized PCa and support the use of such therapy in settings with proven survival benefit.

Topics: Aged; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Flutamide; Follow-Up Studies; Goserelin; Humans; Incidence; Leuprolide; Male; Middle Aged; Proportional Hazards Models; Prostatic Neoplasms; Retrospective Studies; Survival Rate; Time Factors

We did a randomised phase 3 trial assessing the benefit of addition of long-term androgen suppression with a luteinising-hormone-releasing hormone (LHRH) agonist to external irradiation in patients with prostate cancer with high metastatic risk. In this report, we present the 10-year results.. For this open-label randomised trial, eligible patients were younger than 80 years and had newly diagnosed histologically proven T1-2 prostatic adenocarcinoma with WHO histological grade 3 or T3-4 prostatic adenocarcinoma of any histological grade, and a WHO performance status of 0-2. Patients were randomly assigned (1:1) to receive radiotherapy alone or radiotherapy plus immediate androgen suppression. Treatment allocation was open label and used a minimisation algorithm with institution, clinical stage of the disease, results of pelvic-lymph-node dissection, and irradiation fields extension as minimisation factors. Patients were irradiated externally, once a day, 5 days a week, for 7 weeks to a total dose of 50 Gy to the whole pelvis, with an additional 20 Gy to the prostate and seminal vesicles. The LHRH agonist, goserelin acetate (3·6 mg subcutaneously every 4 weeks), was started on the first day of irradiation and continued for 3 years; cyproterone acetate (50 mg orally three times a day) was given for 1 month starting a week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analysis was by intention to treat. The trial is registered at ClinicalTrials.gov, number NCT00849082.. Between May 22, 1987, and Oct 31, 1995, 415 patients were randomly assigned to treatment groups and were included in the analysis (208 radiotherapy alone, 207 combined treatment). Median follow-up was 9·1 years (IQR 5·1-12·6). 10-year clinical disease-free survival was 22·7% (95% CI 16·3-29·7) in the radiotherapy-alone group and 47·7% (39·0-56·0) in the combined treatment group (hazard ratio [HR] 0·42, 95% CI 0·33-0·55, p<0·0001). 10-year overall survival was 39·8% (95% CI 31·9-47·5) in patients receiving radiotherapy alone and 58·1% (49·2-66·0) in those allocated combined treatment (HR 0·60, 95% CI 0·45-0·80, p=0·0004), and 10-year prostate-cancer mortality was 30·4% (95% CI 23·2-37·5) and 10·3% (5·1-15·4), respectively (HR 0·38, 95% CI 0·24-0·60, p<0·0001). No significant difference in cardiovascular mortality was noted between treatment groups both in patients who had cardiovascular problems at study entry (eight of 53 patients in the combined treatment group had a cardiovascular-related cause of death vs 11 of 63 in the radiotherapy group; p=0·60) and in those who did not (14 of 154 vs six of 145; p=0·25). Two fractures were reported in patients allocated combined treatment.. In patients with prostate cancer with high metastatic risk, immediate androgen suppression with an LHRH agonist given during and for 3 years after external irradiation improves 10-year disease-free and overall survival without increasing late cardiovascular toxicity.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Canada; Cardiovascular Diseases; Chemotherapy, Adjuvant; Cyproterone Acetate; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Europe; Fractures, Bone; Goserelin; Humans; Israel; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Neoplasm Staging; Prostatic Neoplasms; Risk Assessment; Russia; Time Factors; Treatment Outcome

Gonadotropin-releasing hormone (GnRH) agonists are associated with greater risk of coronary heart disease and myocardial infarction in men with prostate cancer, but little is known about potential impact on cardiovascular mortality. We assessed the relationship between GnRH agonists and cardiovascular mortality in a large randomized phase III trial of men treated with or without adjuvant goserelin after radiation therapy (RT) for locally advanced prostate cancer.. Between 1987 and 1992, 945 men with locally advanced prostate cancer were randomly assigned to RT and adjuvant goserelin or RT alone. Fine and Gray's regression was used to evaluate treatment effect on cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus (DM), body mass index, race, Gleason score, stage, acid phosphatase level, prostatectomy history, and nodal involvement.. After a median follow-up of 8.1 years, there were 117 cardiovascular-related deaths but no treatment-related increase in cardiovascular mortality. At 9 years, cardiovascular mortality for men receiving adjuvant goserelin was 8.4% v 11.4% for men treated without adjuvant goserelin (Gray's P = .17). In multiple regression analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR] = 0.73; 95% CI, 0.47 to 1.15; P = .16; when censoring at time of salvage goserelin therapy, HR = 0.99; 95% CI, 0.58 to 1.69; P = .97). Traditional cardiac risk factors, including prevalent CVD and DM, were significantly associated with greater cardiovascular mortality.. GnRH agonists do not seem to increase cardiovascular mortality in men with locally advanced prostate cancer. Further studies are warranted to evaluate adverse effects of GnRH agonists in men with lower cancer-specific mortality.

Topics: Adult; Aged; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Goserelin; Humans; Male; Middle Aged; Prostatic Neoplasms; Regression Analysis

Gonadotropin-releasing hormone agonists (GnRHa) are associated with greater risk of coronary heart disease and myocardial infarction in men with prostate cancer, but little is known about their potential effects on cardiovascular mortality. We assessed the relationship between duration of GnRHa therapy and cardiovascular mortality in a large randomized trial of men treated with short-term versus longer-term adjuvant goserelin and radiation therapy (RT) for locally advanced prostate cancer.. From 1992 to 1995, 1554 men with locally advanced prostate cancer (T2c-4, prostate-specific antigen [PSA] <150 ng/ml) received RT and 4 mo of goserelin and then were randomized to no additional therapy (arm 1) or 24 mo adjuvant goserelin (arm 2) in a phase 3 trial (Radiation Therapy Oncology Group [RTOG] 92-02). Cox regression analyses were performed to evaluate the relationship between treatment arm and cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes (DM), race, PSA, Gleason score, and stage.. After median follow-up of 8.1 yr, 185 cardiovascular-related deaths had occurred. No increase in cardiovascular mortality occurred for men receiving a longer duration of goserelin. At 5 yr, cardiovascular mortality for men receiving longer-term adjuvant goserelin was 5.9% versus 4.8% with short-term goserelin (Gray's p=0.16). In multivariate analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR]=1.09; 95% confidence interval [CI], 0.81-1.47; p=0.58; when censoring at time of salvage goserelin, HR=1.02, 95%CI, 0.73-1.43; p=0.9). Traditional cardiac risk factors, including age, prevalent CVD, and DM, were significantly associated with greater cardiovascular mortality.. Longer duration of adjuvant GnRHa therapy does not appear to increase cardiovascular mortality in men with locally advanced prostate cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Flutamide; Goserelin; Humans; Male; Middle Aged; Multivariate Analysis; Prostatic Neoplasms; Time Factors

Low androgen levels in men are associated with increased cardiovascular risk, through unclear mechanisms. We measured arterial stiffness ('compliance') in 21 men receiving complete testosterone suppression therapy for prostate cancer, and in 25 controls. Systemic arterial compliance (SAC), which assesses proximal aortic stiffness, was calculated by simultaneous recording of aortic flow and carotid artery pressure (the 'area method'). Aorto-femoral (A-F), aorto-radial (A-R) and femoral-dorsalis pedis (F-DP) pulse-wave velocities (PWVs) were recorded using the 'Complior' system. SAC was significantly lower in the androgen-depleted men compared to controls (0.81 +/- 0.53 vs. 1.18 +/- 0.43 arbitrary compliance units, p = 0.01, mean +/- SD). Correspondingly, their A-F PWV was higher (14.1 (10.1-21.8) vs. 12.4 (9.6-17.4) m/s, p = 0.03, median (range)). Cases tended to be older (75 +/- 7 vs. 71 +/- 6 years, p = 0.07), and to have higher systolic blood pressure (148 +/- 22 vs. 143 +/- 17 mmHg, p = 0.40); however, SAC was still significantly lower (p = 0.03) after adjustment for age and stratification for central systolic pressure (< or = or > the median). Adjustment of A-F PWV for age and central systolic pressure reduced significance to p = 0.07. There was no significant difference in peripheral PWVs between groups. In conclusion, testosterone suppression is associated with increased aortic stiffness, only partly explained by age and blood pressure. Loss of androgens in men might therefore adversely affect cardiovascular risk.

Topics: Age Factors; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Arteries; Cardiovascular Diseases; Flutamide; Goserelin; Hemodynamics; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms; Vascular Patency

Topics: Androgen Antagonists; Breast; Buserelin; Cardiovascular Diseases; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Goserelin; Humans; Male; Prospective Studies; Prostatic Neoplasms

As androgen deprivation therapy (ADT) is increasingly being used in men with localised prostate cancer, our goal was to examine the association between ADT and the risk of cardiovascular disease (CVD).. We conducted a prospective cohort study using records of a large health-care system in California. The study included men with newly diagnosed localised prostate cancer (1998-2008) who initially underwent active surveillance (N=7637) and were followed through 2010. We examined 10 individual CVD outcomes. Cox proportional hazard models incorporated time-varying treatment variables and controlled for race/ethnicity, age, and tumour characteristics, recurrence risk, CVD medication use, and CVD risk factors.. Of the 7637 subjects, nearly 30% were exposed to ADT. In the multivariable analyses, ADT was associated with an increased risk of heart failure (adjusted HR=1.81, 95% CI 1.40-2.32) in men without preexisting CVD. Elevated risks of arrhythmia (adjusted HR=1.44, 95% CI 1.02-2.01), and conduction disorder (adjusted HR=3.11, 95% CI 1.22, 7.91) were only observed among patients with preexisting CVD.. In men with clinically localised prostate cancer who were initially under active surveillance, ADT was associated with a greater risk of heart failure in men without any preexisting CVD. We also found an increased risk of arrhythmia and conduction disorder in men with preexisting CVD. This study provides the basis for identifying high-risk men treated with ADT who might benefit from regular cardiac monitoring and lifestyle modification recommendations.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Arrhythmias, Cardiac; California; Cardiovascular Diseases; Cohort Studies; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Heart Failure; Humans; Imidazolidines; Leuprolide; Male; Middle Aged; Multivariate Analysis; Neoplasm Grading; Nitriles; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms; Risk Factors; Tosyl Compounds

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Cardiovascular Diseases; Chemotherapy, Adjuvant; Cyproterone Acetate; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Fractures, Bone; Goserelin; Humans; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Neoplasm Staging; Patient Selection; Prostatic Neoplasms; Risk Assessment; Time Factors; Treatment Outcome

Topics: Antineoplastic Agents, Hormonal; Cardiovascular Diseases; Flutamide; Goserelin; Humans; Male; Prostatic Neoplasms