Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: A phase III study.

Non-inferiority in the cumulative castration rate of the 3-month formulation of degarelix compared with the 3-month formulation of goserelin was evaluated in subjects with prostate cancer. A phase III, open-label, parallel-arm study was carried out. An initial dose of 240 mg degarelix or 3.6 mg goserelin was given s.c.; after day 28, a maintenance dose of 480 mg degarelix or 10.8 mg goserelin was given once every 84 days. Non-inferiority in castration rate and safety of degarelix to goserelin were evaluated. The primary end-point was the cumulative castration rate from day 28 to day 364 and the non-inferiority margin was set to be 10%. A total of 234 subjects with prostate cancer were randomized to the degarelix group (n = 117) and the goserelin group (n = 117). The cumulative castration rate was 95.1% in the degarelix group and 100.0% in the goserelin group. As there were no events in the goserelin group, an additional analysis was carried out using 95% confidence intervals of the difference in the proportion of subjects with castration. Analyses indicated the non-inferiority of the 3-month formulation of degarelix to goserelin. Degarelix showed more rapid decreases in testosterone, luteinizing hormone, follicle stimulating hormone, and prostate-specific antigen levels compared with goserelin. The most common adverse events in the degarelix group were injection site reactions. Non-inferiority of the 3-month formulation of degarelix to goserelin was shown for testosterone suppression. The 3-month formulation of degarelix was also found to be tolerated as an androgen deprivation therapy for patients with prostate cancer. This trial was registered with ClinicalTrials.gov (identifier NCT01964170).

[ RANKL antibody for treatment of cancer treatment-induced bone loss (CTIBL)].

Treatment for cancer may cause gonadal dysfunction and bone loss (cancer treatment-induced bone loss ; CTIBL) . Especially, endocrine therapies for breast cancer or prostate cancer carry a significant risk of CTIBL. Therapy-induced premature menopause in premenopausal breast cancer patients, aromatase inhibitor in postmenopausal breast cancer patients, and LHRH agonist with or without anti-androgen in prostate cancer patients may cause bone loss of 5% or more. RANKL (receptor activator of nuclear factor-κB ligand) antibody (denosumab) is effective for prevention of CTIBL and it may prevent CTIBL-induced fracture. During cancer treatment with gonadal dysfunction, bone mineral density should be carefully followed to avoid QOL impairment due to osoteoporosis.

Long-term quality of life outcomes in patients with locally advanced prostate cancer after intensity-modulated radiotherapy combined with androgen deprivation.

With great improvements in survival in patients with locally advanced prostate cancer, quality of life (QOL) is becoming an important factor in the selection of treatment. The aim of this study was to evaluate changes in health-related QOL in patients with locally advanced prostate cancer after intensity-modulated radiotherapy (IMRT) combined with androgen deprivation therapy. Patients were treated with IMRT combined with androgen deprivation. Total dose to the prostate was 68.2 Gy (2.2 Gy per fraction), and patients received 50 mg of oral Casodex once daily and 3.6 mg of subcutaneous Zoladex once every 28 days for 2.5 years. QOL was measured using the Expanded Prostate Cancer Index Composite. The time points were baseline, end of radiotherapy, and 3, 12, 36, 48, and 60 months after radiotherapy. From 2002 to 2007, a total of 87 patients were enrolled. Median follow-up time was 76.8 months. Compared with baseline, all four domain summary scores were decreased to varying degrees. Statistically significant changes in the urinary, bowel, and hormonal domain scores were observed (P < 0.05). The changes in scores for urinary incontinence and dysuria were -13.0 ± 8.3 and -6.12 ± 3.9, respectively (P < 0.05). QOL was decreased in patients with locally advanced prostate cancer after IMRT combined with androgen deprivation therapy in all four primary domains, especially in urinary, bowel, and hormonal domains. Nevertheless, the treatment was well tolerated in most patients during the 5 years of follow-up.

Adjuvant chemotherapy followed by goserelin compared with either modality alone: the impact on amenorrhea, hot flashes, and quality of life in premenopausal patients--the International Breast Cancer Study Group Trial VIII.

PURPOSE: The purpose of this article is to compare quality of life (QOL) and menopausal symptoms among premenopausal patients with lymph node-negative breast cancer receiving chemotherapy, goserelin, or their sequential combination, and to investigate differential effects by age. PATIENTS AND METHODS: We evaluated QOL data from 874 pre- and perimenopausal women with lymph node-negative breast cancer who were randomly assigned to receive six courses of classical cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy, ovarian suppression with goserelin for 24 months, or six courses of classical CMF followed by 18 months of goserelin. We report QOL data collected during 3 years after random assignment in patients without disease recurrence. RESULTS: Overall, patients receiving goserelin alone showed a marked improvement or less deterioration in QOL measures over the first 6 months than those patients treated with CMF. There were no differences at 3 years after random assignment according to treatment except for hot flashes. As reflected in the hot flashes scores, patients in all three treatment groups experienced induced amenorrhea, but the onset of ovarian function suppression was slightly delayed for patients receiving chemotherapy. Younger patients (< 40 years) who received goserelin alone returned to their premenopausal status at 6 months after the cessation of therapy, while those who received CMF showed marginal changes from their baseline hot flashes scores. CONCLUSION: Age-adjusted risk profiles that consider patient-reported outcomes enable patients to adapt to their disease and treatment, such as considering the trade-offs between delayed endocrine symptoms, but higher risk of permanent menopause with chemotherapy, and immediate but reversible endocrine symptoms with goserelin, in younger premenopausal patients.

Zoledronic acid prevents cancer treatment-induced bone loss in premenopausal women receiving adjuvant endocrine therapy for hormone-responsive breast cancer: a report from the Austrian Breast and Colorectal Cancer Study Group.

PURPOSE: Adjuvant therapy for breast cancer can be associated with decreased bone mineral density (BMD) that may lead to skeletal morbidity. This study examined whether zoledronic acid can prevent bone loss associated with adjuvant endocrine therapy in premenopausal patients. PATIENTS AND METHODS: This study is a randomized, open-label, phase III, four-arm trial comparing tamoxifen (20 mg/d orally) and goserelin (3.6 mg every 28 days subcutaneously) +/- zoledronic acid (4 mg intravenously every 6 months) versus anastrozole (1 mg/d orally) and goserelin +/- zoledronic acid for 3 years in premenopausal women with hormone-responsive breast cancer. In a BMD subprotocol at three trial centers, patients underwent serial BMD measurements at 0, 6, 12, 24, and 36 months. RESULTS: Four hundred one patients were included in the BMD subprotocol. Endocrine treatment without zoledronic acid led to significant (P < .001) overall bone loss after 3 years of treatment (BMD, -14.4% after 36 months; mean T score reduction, -1.4). Overall bone loss was significantly more severe in patients receiving anastrozole/goserelin (BMD, -17.3%; mean T score reduction, -2.6) compared with patients receiving tamoxifen/goserelin (BMD, -11.6%; mean T score reduction, -1.1). In contrast, BMD remained stable in zoledronic acid-treated patients (P < .0001 compared with endocrine therapy alone). No interactions with age or other risk factors were noted. CONCLUSION: Endocrine therapy caused significant bone loss that increased with treatment duration in premenopausal women with breast cancer. Zoledronic acid 4 mg every 6 months effectively inhibited bone loss. Regular BMD measurements and initiation of concomitant bisphosphonate therapy on evidence of bone loss should be considered for patients undergoing endocrine therapy.

Resultados en el tratamiento de la endometrosis con cirugía y análogos del GnRh de depósito / Surgical treatment of the endometrosis compared to the treatment whith GnRh analogues

Muestra nuestra experiencia en el tratamiento secuencial y combinado, quirúrgico y médico con análogos del GnRh de depósito (Lupron 3,75), hiperestimulación ovárica controlada con gonadotrofinas HMG-HCG y posterior Second Look laparoscópico con técnica de transferencia intratubaria de gametos. Se evaluó 61 pacientes que consultaron por infertilidad en el Instituto de Ginecología y Fertilidad de Bs. As., entre el 1º de octubre de 1992 y el 30 de diciembre de 1994. En todas ellas se realizó una laparoscopia para el diagnóstico y estadificación de la endometrosis según la clasificación revisada de la Sociedad Americana de Fertilidad, realizándose en el mismo acto los procedimientos quirúrgicos de coagulación, lisis o quistectomía según fuera necesario. Todas las pacientes fueron medicadas con Lupron 3,75 de aplicación mensual durante un período de 6 meses posteriores a la cirugía. Del total de 61 pacientes, 29 (47,5 por ciento) se embarazaron con tratamiento quirúrgico, médico e hiperestimulación ovárica, de las cuales 17 (59 por ciento) lo logró en forma espontánea, 13 (44,8 por ciento) en el primer semestre y 4 (13,7 por ciento) en el segundo semestre postratamiento. Sobre 35 pacientes estimuladas, a partir de los 6 meses de finalizado el Lupron por un período de 3,2 ciclos se embarazaron 12 (41 por ciento). A 10 pacientes se les realizó al cabo de un año de finalizado el tratamiento con análogos un second look laparoscópico con técnica de transferencia intratubaria de gametos, logrando el embarazo en 5 pacientes (50 por ciento). Los resultados obtenidos sugieren que el tratamiento propuesto ha sido útil en este grupo de pacientes, logrando además una adecuada tolerancia y aceptación por parte de las mismas