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PURPOSE: Although different gonadotropin-releasing hormone (GnRH) agonists may have different effects, their effect of ovarian protection during chemotherapy for breast cancer has not been compared. This study aimed to compare the effects of goserelin and leuprorelin for ovarian protection during chemotherapy in young patients with breast cancer. METHODS: This prospective study analyzed 193 patients with breast cancer aged ≤ 40 years who had regular menstruation and serum anti-Müllerian hormone (AMH) levels ≥ 1 ng/mL before treatment. Patients received either goserelin or leuprorelin for ovarian protection during doxorubicin/cyclophosphamide-based chemotherapy. Resumption of menstruation and changes in serum levels of AMH were compared between the two groups at 12 months after completion of chemotherapy. RESULTS: The mean age and the pretreatment serum AMH level were 33.2 years and 4.4 ng/mL in goserelin group and 34.2 years and 4.0 ng/mL in leuprorelin group. The proportion of patients who resumed menstruation was not different between the goserelin (94.4%) and leuprorelin (95.3%) groups at 12 months after chemotherapy completion. Serum AMH levels decreased significantly in both the goserelin (from 4.4 to 1.2 ng/mL) and leuprorelin (from 4.0 to 1.2 ng/mL) groups, with no statistical significance. In addition, no difference was found in the proportion of patients with serum AMH levels ≥ 1 ng/mL between the goserelin (49.5%) and leuprorelin (44.2%) groups at 12 months after chemotherapy. CONCLUSION: Goserelin and leuprorelin were comparable in terms of ovarian protection during doxorubicin/cyclophosphamide-based chemotherapy in young patients with breast cancer.
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Neoplasias da Mama , Hormônios Peptídicos , Feminino , Humanos , Gosserrelina/efeitos adversos , Leuprolida/uso terapêutico , Estudos Prospectivos , Ciclofosfamida/efeitos adversos , Doxorrubicina/efeitos adversosRESUMO
Androgen deprivation therapy (ADT) in men with prostate cancer (PCa) is associated with significant side effects. With the transition of PCa from a foudroyant course to a chronic disease, managing these side effects has become increasingly important. There is growing evidence that nutritional changes and physical activity are beneficial in these patients. Here we examine the impact of written patient information on the physical activity and dietary habits of PCa patients receiving ADT and behaviour changes between baseline and 1 year, in the open-label, non-interventional LEAN study. In total, 959 patients with advanced hormone-sensitive PCa requiring ADT with the Leuprorelin Sandoz® implant were included from January 2014 to July 2015 and followed for ≥ 12 months. At the start of the study, urologists received a questionnaire concerning the written information provided to patients regarding their disease, patient advocacy groups, diet and physical activity. Patients received a questionnaire on their dietary habits and physical activity at the start and end of the study. Urologists from 147 study centres and 540 patients responded to the questionnaires. While 69 % of these patients received disease-specific information, only 30 % and 17 % received information regarding nutrition and physical activity, respectively. The majority of urologists estimate that their patients rarely or never follow guidance on nutrition or physical activity, yet > 90 % of patients indicate they would make use of this information, if provided. Few patients showed behavioural changes between baseline and 1 year without evident differences between patients that received information and those that did not.
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Neoplasias da Próstata , Humanos , Masculino , Antagonistas de Androgênios/efeitos adversos , Estilo de Vida , Neoplasias da Próstata/tratamento farmacológicoRESUMO
OBJECTIVE: This multicenter, retrospective, observational study investigated baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer who received primary androgen deprivation therapy, using Japan Study Group of Prostate Cancer registry data. METHODS: Among patients in the Japan Study Group of Prostate Cancer registry, those who initiated primary androgen deprivation therapy and were aged 20 years or older were enrolled in this study. The primary endpoint was time to disease progression, defined as time from primary androgen deprivation therapy initiation to either prostate-specific antigen or clinical progression. Secondary endpoints included prostate-specific antigen progression-free survival, prostate-specific antigen response (90% or greater reduction from baseline) and distribution of second-line treatment. RESULTS: Of the 2494 patients (goserelin, n = 564; leuprorelin, n = 1148; surgical castration, n = 161; degarelix, n = 621), those who received degarelix had higher prostate-specific antigen levels and Gleason scores and were at a more advanced clinical stage than those receiving goserelin or leuprorelin. The median time to disease progression (identical to the prostate-specific antigen progression-free survival result) was not reached for goserelin and leuprorelin, 52.7 months for surgical castration and 54.0 months for degarelix. Although baseline prostate-specific antigen values in the degarelix cohort were higher than those of the leuprorelin or goserelin cohorts, prostate-specific antigen responses were not different among the three cohorts. Regarding second-line treatment, the largest patient group received degarelix followed by leuprorelin (n = 195). CONCLUSIONS: This study clarified patient characteristics and long-term effectiveness of primary androgen deprivation therapy in real-world clinical practice. Japanese urologists appear to select appropriate primary androgen deprivation therapy based on patient background and tumour characteristics, with degarelix largely reserved for higher risk patients.
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Triptorelin and leuprorelin are synthetic gonadotrophin-releasing hormones (GnRH) that are on the World Anti-Doping Agency (WADA) list of prohibited substances. To investigate the possible in vivo metabolites of triptorelin and leuprorelin in humans compared to previously reported in vitro metabolites, excreted urine from five patients treated with either triptorelin or leuprorelin was analyzed by liquid chromatography coupled with ion trap/time-of-flight mass spectrometry (LC/MS-IT-TOF). The addition of dimethyl sulfoxide (DMSO) to the mobile phase was found to enhance the detection sensitivity of certain GnRH analogs. The method was validated, and the limit of detection (LOD) was found at 0.02-0.08 ng/mL. Using this method, a novel new metabolite of triptorelin was discovered in the urine of all subjects up to 1 month after triptorelin administration, but it was not observed in the urine of subjects before drug administration. The limit of detection was estimated to be 0.05 ng/mL. The structure of the metabolite, triptorelin (5-10), is proposed from bottom-up mass spectrometry analysis. The discovery of in vivo triptorelin (5-10) can possibly be used as supporting evidence of triptorelin misuse in athletes.
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Dimetil Sulfóxido , Pamoato de Triptorrelina , Humanos , Leuprolida , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida/métodos , Hormônio Liberador de GonadotropinaRESUMO
AIM: To investigate the efficacy of short-term administration of relugolix, a novel orally active gonadotropin-releasing hormone (GnRH) antagonist, before single-port laparoscopic-assisted vaginal hysterectomy (LAVH) for symptomatic uterine myomas, retrospectively compared with injection of leuprorelin, a GnRH agonist. METHODS: A retrospective comparative study of each 35 women with symptomatic myomas in the relugolix and leuprorelin groups. RESULTS: Before administration of relugolix and leuprorelin, the median uterine volume did not differ significantly between the two groups (p = 0.53). Median uterine volume change from baseline after short-term administration of relugolix and leuprorelin did not differ significantly (p = 0.17). Surgical duration (p = 0.84) and estimated blood loss (p = 0.48) were not different between the two groups. According to a patient questionnaire, the side effects of the drugs were not different between the two groups (p = 0.27). When patients were was asked if they wanted to have either of these drugs again, some relugolix users preferred leuprorelin due to concern about forgetting daily medication, while some leuprorelin users preferred relugolix to avoid pain at injection. CONCLUSION: Oral relugolix medication or leuprorelin injection administered before single-port LAVH for uterine myomas yielded an equivalent reduction of uterine volume and perioperative outcomes with no significant adverse events. Patient preference for either oral daily relugolix or a monthly injection of leuprorelin could be considered when preoperative management is determined.
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Laparoscopia , Leiomioma , Mioma , Neoplasias Uterinas , Feminino , Humanos , Histerectomia Vaginal , Leiomioma/tratamento farmacológico , Leiomioma/cirurgia , Leuprolida/uso terapêutico , Mioma/cirurgia , Compostos de Fenilureia , Pirimidinonas , Estudos Retrospectivos , Neoplasias Uterinas/tratamento farmacológico , Neoplasias Uterinas/cirurgiaRESUMO
BACKGROUND: Relugolix is a once-daily, oral, nonpeptide, gonadotropin-releasing hormone receptor antagonist. The aim of this study was to evaluate safety of relugolix over 24 weeks in women with endometriosis-associated pain. METHODS: This phase 2, randomized, open-label, parallel-group extension study was conducted in 101 clinics in Japan. Patients (premenopausal females ≥ 20 years) who completed the preceding 12-week relugolix phase 2 study continued to receive relugolix (10 mg, 20 mg, or 40 mg), placebo, or leuprorelin (3.75 mg) for an additional 12 weeks. Relugolix was administered orally once daily, and leuprorelin subcutaneously once every 4 weeks. The primary outcome was safety, including bone mineral density (BMD) and treatment-emergent adverse events (TEAEs). Secondary endpoints included visual analog scale (VAS) scores for endometriosis-associated pain. Analysis sets were defined as all patients who were administered the study drug. RESULTS: Of 487 randomized patients in the preceding study, 397 enrolled in this extension study and continued to receive placebo (n = 77), relugolix 10 mg (n = 84), relugolix 20 mg (n = 78), relugolix 40 mg (n = 89), or leuprorelin (n = 69). Baseline characteristics were similar between extension study patients and patients in the preceding study. Frequency of TEAEs including metrorrhagia, menorrhagia, and hot flush was similar in the relugolix 40-mg and leuprorelin groups. Mean (SD) change in BMD from baseline at Week 24 was - 0.2 (1.99)% for placebo; - 1.6 (2.34)%, - 2.6 (2.94)%, and - 4.9 (2.91)% for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and - 4.4 (2.16)% for leuprorelin. Mean ± SD change from baseline in mean VAS score (mm) for pelvic pain at end of treatment was - 3.2 ± 12.16 for placebo; - 6.8 ± 10.56, - 9.0 ± 11.84, and - 11.9 ± 11.26 for the relugolix 10-mg, 20-mg, and 40-mg groups, respectively; and - 12.7 ± 12.57 for leuprorelin. Estradiol levels decreased with increasing relugolix dose and remained below postmenopausal levels throughout the 24-week relugolix 40-mg treatment period. CONCLUSIONS: Treatment with relugolix for 24 weeks was generally well tolerated and demonstrated similar pain reduction to leuprorelin in women with endometriosis. The dose-dependent loss in BMD observed with relugolix treatment was expected due to an induced hypoestrogenic state. Relugolix demonstrated a similar benefit/risk profile to injectable therapy in this phase 2 study. Trial registration NCT01452685 (ClinicalTrials.gov, registered 17/10/2011).
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Endometriose , Método Duplo-Cego , Endometriose/complicações , Endometriose/tratamento farmacológico , Feminino , Humanos , Japão , Leuprolida/uso terapêutico , Dor Pélvica/tratamento farmacológico , Dor Pélvica/etiologia , Compostos de Fenilureia , Pirimidinonas , Resultado do TratamentoRESUMO
BACKGROUND: Observational studies generate information on real-world therapy and complement data from prospective randomized trials. LEAN is an open-label, non-interventional, multi-centre, German cohort study on leuprorelin in routine clinical practice. OBJECTIVES: To extend knowledge on the use, effectiveness, and tolerability of HEXAL/Sandoz leuprorelin (in this article, the term Leuprone® HEXAL® covers Leuprorelin Sandoz® as well) solid implant in patients with prostate cancer (PCa) in a real-world setting. METHODS: 959 PCa patients scheduled for androgen deprivation therapy (ADT) received leuprorelin acetate implant. Metabolism, serum prostate-specific antigen (PSA), and testosterone data, if available, were collected at baseline and follow-up visits for ≥12 months. RESULTS: Of 694 patients in the modified full analysis set, 26.4% received GnRH analogues ≤6 months before enrolment. Fifty-one percent of patients were treated for locally advanced or metastatic PCa. In 19.6% of patients, ADT was used in neoadjuvant or adjuvant settings and in 28.5% with rising PSA after definite therapy. Testosterone levels <0.5 ng/mL were achieved in >90% of patients. Safety profile was in line with the summary of product characteristics. Therapy was well tolerated, with patient-triggered therapy discontinuation in 3.6%. CONCLUSIONS: This interim analysis confirmed previous efficacy findings for leuprorelin implant in a real-world setting. This contemporary cohort showed a shift in the use of ADT to non-metastatic PCa stages.
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Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Leuprolida/uso terapêutico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/tratamento farmacológico , Testosterona/sangue , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Alemanha , Humanos , Masculino , Fatores de Tempo , Resultado do TratamentoRESUMO
Intermittent androgen deprivation therapy with gonadotropin-releasing-hormone (GnRH) agonists can prevent or delay disease progression and development of castration resistant prostate cancer for subpopulations of prostate cancer patients. It may also reduce risk and severity of side effects associated with chemical castration in prostate cancer (PCa) patients. One of the earliest comprehensively documented clinical trials on this was reported in a Canadian patient population treated with leuprorelin preceded by a lead-in with cyproterone acetate. A systems-based mixed effect analysis of testosterone response in active and recovery phases allows inference of new information from this patient population. Efficacy of androgen deprivation therapy is presumed to depend on a treshold value for testosterone at the nadir, below which no additional beneficial effects on PSA reponse can be expected, and occurance of testosterone breakthroughs during active therapy. The present analysis results in a mixed effect model, incorporating GnRH receptor activation, testosterone turnover and feedback mechanisms, describing and predicting testosterone inhibition under intermittent androgen deprivation therapy on the individual and population level, during multiple years of therapy. Testosterone levels in these patients decline over time with an estimated first order rate constant of 0.083 year-1(T1/2 = 8.4 y), with a substantial distribution among this patient population, compared to the general population. PCa patients leaving the trial due to unmanageble PSA relapse appear to have slightly higher testosterone levels at the nadir than sustained responders. These findings are expected to contribute to an increased understanding of the role of testosterone in long term disease progression of prostate cancer.
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Antagonistas de Androgênios/uso terapêutico , Hormônio Liberador de Gonadotropina/agonistas , Neoplasias da Próstata/tratamento farmacológico , Testosterona/antagonistas & inibidores , Idoso , Antagonistas de Androgênios/administração & dosagem , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/farmacologia , Acetato de Ciproterona/administração & dosagem , Acetato de Ciproterona/efeitos adversos , Acetato de Ciproterona/uso terapêutico , Humanos , Leuprolida/administração & dosagem , Leuprolida/efeitos adversos , Leuprolida/uso terapêutico , Masculino , Antígeno Prostático Específico/sangue , Testosterona/sangue , Resultado do TratamentoRESUMO
AIMS: This investigation aimed to quantitatively characterize the relationship between the gonadotropin-releasing hormone agonist leuprorelin, testosterone (T) and prostate specific antigen (PSA) concentrations over time, to aid identification of a target T concentration that optimises the balance of the benefits of T suppression whilst reducing the risk of side effects related to futile over-suppression. METHODS: Data from a single dose study to investigate the effect of leuprorelin in a 6-month depot formulation on T and PSA in prostate cancer patients were analysed using a population pharmacokinetic-pharmacodynamic modelling approach. The developed model was qualified using external data from 3 studies, in which the effect of different formulations of leuprorelin on T and PSA was evaluated in prostate cancer patients. RESULTS: The effect of leuprorelin on the relationship between T and PSA was adequately characterized by the Romero model with minor modifications, combined with a turnover model to describe the delay in response between T and PSA. The data were significantly better described when assuming a minimum PSA level that is independent on the treatment-related reduction in T, as compared to a model with a proportional reduction in PSA and T. CONCLUSIONS: The model-based analysis suggests that on a population level, reducing T concentrations below 35 ng/dL does not result in a further decrease in PSA levels (>95% of the minimal PSA level is reached). More data are required to support this relationship in the lower T and PSA range.
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Antineoplásicos Hormonais/farmacocinética , Calicreínas/sangue , Leuprolida/farmacocinética , Modelos Biológicos , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Testosterona/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Monitoramento de Medicamentos , Humanos , Leuprolida/administração & dosagem , Leuprolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Neoplasias da Próstata/sangue , Neoplasias da Próstata/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto JovemRESUMO
We aimed to examine how leuprorelin has been studied for the treatment of women with endometriosis in Asia. We conducted a literature search of PubMed, the Cochrane Library and ClinicalTrials.gov. This review includes randomised trials of women with endometriosis treated with leuprorelin in Asia. Phase I-IV clinical trials published between January 1 2000 and December 31 2016 and written in English were included. Four studies were identified, showing that leuprorelin significantly improves pain and quality of life. The oestrone and oestradiol levels are decreased by leuprorelin but can be increased using an 'add-back' therapy with conjugated equine oestrogen and methoxyprogesterone. Menopause is more common in women treated with leuprorelin. The bone mineral density is reduced in women treated with leuprorelin. There are limited studies investigating the use of leuprorelin for the treatment of endometriosis in Asian populations. However, the research that has been conducted supports the use of leuprorelin in an Asian population.
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Endometriose/tratamento farmacológico , Leuprolida/uso terapêutico , Povo Asiático , Feminino , Gonadotropinas/sangue , Humanos , Dor/tratamento farmacológicoRESUMO
Paraphilia is a complex psychological and psychiatric disorder that has been difficult to treat. Leuprorelin has been used as one of the therapeutic methods for paraphilia. Leuprorelin administration could change insulin resistance and accelerate bone loss. The case study in this work was a 59-year-old man who visited a hospital with the chief complaints of frotteuristic behaviors in public places, a continuous increase in sexual desire, and sexual molestation behavior that started in 2007. We injected leuprorelin (3.6 mg) intramuscularly every month for this patient with paraphilia and comorbidities of osteoporosis and hyperthyroidism. The clinical global impression (CGI), Sex Addiction Screening Test (SAST), Wilson Sex Fantasy Questionnaire (WSFQ), physical examination, and laboratory tests were performed. After 12 months of leuprorelin injection for paraphilia, we found a significant improvement in abnormal sexual behavior/desire without aggravation of osteoporosis/hyperthyroidism. Gonadotrophin-Releasing Hormone (GnRH) analogs could be used as alternative or supplementary treatment methods for paraphilia with osteoporosis/hyperthyroidism.
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Leuprolida/efeitos adversos , Leuprolida/uso terapêutico , Osteoporose/etiologia , Transtornos Parafílicos/tratamento farmacológico , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/uso terapêutico , Humanos , Leuprolida/farmacologia , Masculino , Pessoa de Meia-IdadeRESUMO
To review direct comparative studies of the gonadotrophin-releasing hormone (GnRH) agonists goserelin, triptorelin, and leuprorelin for the treatment of prostate cancer, and identify whether there are meaningful clinical differences between these agents. In June 2017, the following searches were performed independently by two reviewers in PubMed: (i) 'prostate cancer' and 'triptorelin' and 'leuprorelin', (ii) 'prostate cancer' and 'triptorelin' and 'goserelin', and (iii) 'prostate cancer' and 'goserelin' and 'leuprorelin', without time restriction. Duplicates were deleted. Relevant conference abstracts were also screened. A total of 16 direct comparative trials were identified: 12 reported on efficacy outcomes, four on safety/tolerability, and five on the convenience of administration/user perceptions. These studies are restricted in terms of patient numbers, formulations assessed, and endpoints measured; none were adequately powered for survival outcome measures. Studies reporting on efficacy endpoints did not show major differences in the ability of these GnRH agonists to reduce levels of testosterone or prostate-specific antigen. Some studies suggest differences in short- or long-term testosterone control, the rate of injection site adverse events, and patient/healthcare professional perceptions, but definitive conclusions cannot be drawn from the existing evidence. Few direct comparative trials of GnRH agonists have been conducted. Whilst GnRH agonists provide a similar castration effect, there is not enough evidence to show that GnRH agonists are equivalent.
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Antineoplásicos Hormonais/uso terapêutico , Gosserrelina/uso terapêutico , Leuprolida/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Pamoato de Triptorrelina/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Hormônio Liberador de Gonadotropina/agonistas , Gosserrelina/efeitos adversos , Humanos , Leuprolida/efeitos adversos , Masculino , Neoplasias da Próstata/mortalidade , Taxa de Sobrevida , Testosterona/sangue , Resultado do Tratamento , Pamoato de Triptorrelina/efeitos adversosRESUMO
In women, breast cancer is the most common cancer diagnosis and second most common cause of cancer death. More than half of breast cancer patients will develop metastases to the bone, liver, lung, or brain. Breast cancer brain metastases (BCBM) confers a poor prognosis, as current therapeutic options of surgery, radiation, and chemotherapy rarely significantly extend life and are considered palliative. Within the realm of chemotherapy, the last decade has seen an explosion of novel chemotherapeutics involving targeting agents and unique dosage forms. We provide a historical overview of BCBM chemotherapy, review the mechanisms of new agents such as poly-ADP ribose polymerase inhibitors, cyclin-dependent kinase 4/6 inhibitors, phosphatidyl inositol 3-kinaseinhibitors, estrogen pathway antagonists for hormone-receptor positive BCBM; tyrosine kinase inhibitors, antibodies, and conjugates for HER2+ BCBM; repurposed cytotoxic chemotherapy for triple negative BCBM; and the utilization of these new agents and formulations in ongoing clinical trials. The mechanisms of novel dosage formulations such as nanoparticles, liposomes, pegylation, the concepts of enhanced permeation and retention, and drugs utilizing these concepts involved in clinical trials are also discussed. These new treatments provide a promising outlook in the treatment of BCBM.
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Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Barreira Hematoencefálica/metabolismo , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/secundário , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Sistemas de Liberação de Medicamentos , HumanosRESUMO
BACKGROUND: We conducted an open-label, randomized controlled trial evaluating the appropriate treatment duration of leuprorelin acetate 3-month depot, TAP-144-SR (3M), administered postsurgically every 3 months for 2 years versus 3 or more (up to 5) years, in combination with tamoxifen, for 5 years in premenopausal endocrine-responsive breast cancer patients and reported similar survival benefit in the two treatment groups. We hereby present patient-reported quality of life (QOL) data obtained from this trial. METHODS: Three self-administered QOL questionnaires (QOL-ACD, QOL-ACD-B, FACT-ES subscale) were used, and the difference in QOL score changes between the two groups was analyzed using a mixed-effects model for repeated measures. RESULTS: Eligible patients (N = 222) were randomly assigned to a 2-year (2YG, N = 112) or 3-or-more-year treatment group (3YG, N = 110). The time courses of the three QOL scores during the trial period were similar in the two groups. The mean changes in the QOL scores from week 96 were largely stable through week 240 in the 3YG, but showed significantly greater improvement in the score changes from week 96 in the 2YG than the 3YG. Symptoms associated with menopause such as hot flashes and sweating contributed to these results. Menstruation recovery was associated with significantly greater improvement of these symptoms in the 2YG than the 3YG. CONCLUSIONS: Patient-reported menopause-associated symptoms and QOL improved after discontinuation of the LH-RH agonist administration and menstruation recovery. QOL information should be a consideration in long-term treatment.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Leuprolida/uso terapêutico , Qualidade de Vida/psicologia , Tamoxifeno/uso terapêutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Neoplasias da Mama/patologia , Feminino , Humanos , Leuprolida/administração & dosagem , Leuprolida/farmacologia , Pessoa de Meia-Idade , Pré-Menopausa , Tamoxifeno/administração & dosagem , Tamoxifeno/farmacologia , Resultado do TratamentoRESUMO
INTRODUCTION: We investigated the health-related quality of life (HRQoL) of long-term prostate cancer patients who received leuprorelin acetate in microcapsules (LAM) for androgen-deprivation therapy (ADT). METHODS: The observational study was carried out by 30 office-based German urologists in 536 prostate cancer (PCa) patients treated for ≥5 years with LAM and in 116 patients of an age-matched control group (CG). Data on HRQoL and health status was collected prospectively using validated questionnaires QLQ-C30, QLQ-PR25 and Karnofsky Index. Data on effectiveness (clinical response, prostate specific antigen [PSA], testosterone) and safety was collected retrospectively from patients' health records. We used descriptive statistics to analyze the data. RESULTS: The mean treatment duration was 8.6 years (range 4.5-19.8 years). General health status (QLQ-C30) was comparable for both groups. Differences were observed regarding physical - and role functioning. ADT patients rated single items slightly worse than CG. Karnofsky-Index showed comparable high values (median of 90%). QLQ-PR25 revealed more PCa-related symptoms for ADT patients. Within 6 months, median PSA level declined >90% and median testosterone levels declined below castration level from 4.0 to 0.2 ng/mL. Clinical response (European Organisation for Research and Treatment of Cancer criteria) was observed in at least 90% of ADT patients. CONCLUSIONS: Long-term ADT with LAM is a well-accepted, tolerated, effective, and low-burden treatment option for patients with advanced, hormone-sensitive PCa.
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Antineoplásicos Hormonais/uso terapêutico , Leuprolida/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Sobreviventes de Câncer , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: This study examined the clinical effects of leuprolide acetate in sexual offenders with paraphilic disorders evaluated by means of objective psychiatric assessment. METHODS: The subjects of this study were seven sexual offenders who were being treated by means of an injection for sexual impulse control by a court order. They had been diagnosed with paraphilia by a psychiatrist based on the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and had been put on probation by the Ministry of Justice between January 2016 and December 2016. RESULTS: After twelve months, we observed significant improvement in symptoms, as decrease of abnormal sexual interest and activity, sexual fantasy, Clinical Global Impression-Severity (CGI-S), and Clinical Global Impression-Impulsivity (GCI-I). There were a mild feminization of the body shape, feelings of fatigue, and mild hot flushes. No other adverse effect was reported. CONCLUSION: These results suggested that the clinical effects of leuprolide acetate in sexual offenders might be an effective treatment and safety strategy.
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Delitos Sexuais , Adulto , Criminosos , Manual Diagnóstico e Estatístico de Transtornos Mentais , Humanos , Leuprolida , Pessoa de Meia-Idade , Transtornos ParafílicosRESUMO
OBJECTIVE: Leuprorelin acetate (TAP-144-SR) is commonly used worldwide in prostate cancer patients. This study was conducted to assess the non-inferiority of a 6-month depot formulation of TAP-144-SR (TAP-144-SR [6M]) 22.5 mg to a 3-month depot formulation of TAP-144-SR (TAP-144-SR [3M]) 11.25 mg in prostate cancer patients in Japan. METHODS: This was a 48-week Phase III, open-label, parallel-group comparative study. TAP-144-SR (6M) 22.5 mg (6M group) and TAP-144-SR (3M) 11.25 mg (3M group) were administered to 81 and 79 subjects, respectively. The primary endpoint was the rate of serum testosterone suppression to the castrate level (≤100 ng/dl). RESULTS: Serum testosterone of all subjects excluding one subject in the 3M group was suppressed to the castrate level throughout 48 weeks. The estimated between-group difference (6M group - 3M group) in suppression rate was 1.3% (95% confidence interval: -3.4, 6.8), and its lower confidence interval was more than -10% of the pre-determined allowable limit value to judge the non-inferiority. The prostate-specific antigen concentrations were stable throughout the study in both groups. Progressive disease in the best overall response based on the Response Evaluation Criteria In Solid Tumors was 0.0% for the 6M group and 2.6% for the 3M group. Adverse events occurred in 92.6% in the 6M group and 89.9% in the 3M group. Adverse events leading to discontinuation were reported in 2.5% in the 6M group and 3.8% in the 3M group. CONCLUSIONS: TAP-144-SR (6M) was not inferior to TAP-144-SR (3M) for the suppressive effect on serum testosterone level. TAP-144-SR (6M) was also as well tolerated as TAP-144-SR (3M).
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Leuprolida/uso terapêutico , Neoplasias da Próstata/sangue , Neoplasias da Próstata/tratamento farmacológico , Testosterona/sangue , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/efeitos adversos , Biomarcadores Tumorais/sangue , Preparações de Ação Retardada/administração & dosagem , Humanos , Japão , Leuprolida/administração & dosagem , Leuprolida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Antígeno Prostático Específico/sangue , Projetos de Pesquisa , Resultado do TratamentoRESUMO
Paraphilia is a psychiatric disease that has been difficult to cure. However, recently developed therapeutic methods hold promise. The patient was a 20-yr-old male with chief complaints of continuous masturbation, genital exposure, and aggressive behavior that started 2 yr ago. We administered leuprorelin 3.6 mg intramuscular injection per month, a depot gonadotrophin-releasing hormone analogue, to this patient who a severe mentally retardation with paraphilia. The clinical global impression (CGI)-severity, CGI-improvement and aberrant behavior checklist were performed. After one month, we observed significant improvement in symptoms, such as decreases of abnormal sexual behavior and sexual desire. The GnRH analogues are suggested to be used as an alternative or supplementary therapeutic method for sexual offenders after clinical studies.
Assuntos
Leuprolida/uso terapêutico , Transtornos Mentais/tratamento farmacológico , Transtornos Parafílicos/tratamento farmacológico , Humanos , Leuprolida/farmacologia , Masculino , Transtornos Mentais/complicações , Transtornos Mentais/diagnóstico , Transtornos Parafílicos/complicações , Transtornos Parafílicos/diagnóstico , Delitos Sexuais/prevenção & controle , Comportamento Sexual/efeitos dos fármacos , Adulto JovemRESUMO
Objective: To investigate the effects of combining gonadotropin-releasing hormone agonist (GnRHa) downregulation with hormone replacement therapy (HRT, GnRHa-HRT) on the clinical outcomes of patients undergoing frozen-thawed embryo transfer (FET). Methods: In this retrospective study, we included patients who had FET between January 2018 and December 2022. They were categorized into HRT and GnRHa-HRT groups based on the endometrial preparation protocol. The study compared the clinical outcomes of patients in two groups. Possible factors affecting clinical outcomes were analyzed using univariate analysis. To analyze the impact of two endometrial preparation methods on clinical outcomes, multifactorial logistic regression was performed. Results: The rates of clinical pregnancy (47.31% vs. 59.60%), embryo implantation (37.58% vs. 49.65%), biochemical pregnancy (52.36% vs. 64.31%), and early abortion (7.07% vs. 10.77%) were statistically different between the two groups (p < 0.05). Analysis using multifactorial logistic regression showed that there was a 1.65-fold increase in clinical pregnancy rates (OR = 1.65, 95% CI: 1.29-2.12, p < 0.001) and a 1.55-fold increase in embryo implantation rates (OR = 1.55, 95% CI: 1.27-1.90, p < 0.001) in the GnRHa-HRT group when compared to the HRT group. For blastocyst transfer, the clinical pregnancy and implantation rates of the GnRHa-HRT group were significantly higher than those of the HRT group (OR = 1.75, 95% CI: 1.30-2.37, p < 0.001; OR = 1.73, 95% CI: 1.35-2.21, p < 0.001). Conclusion: In FET cycles, leuprorelin (as a GnRHa) downregulation combined with HRT may improve the clinical outcome of patients compared to the HRT cycle, especially for the clinical pregnancy and embryo implantation rates of patients with blastocyst transfer.
RESUMO
Leuprorelin acetate is a common anticancer medication used for prostate cancer treatment. One of the local adverse reactions after leuprorelin injection is the development of reactive granulomas, typically presenting as subcutaneous nodules. In this case report, we describe a 73-year-old patient with prostate cancer who developed unusually large sized intramuscular reactive granulomas, which mimicked malignant soft tissue tumors. The patient, who had been receiving leuprorelin acetate treatment for the past 12 months, noticed painful masses in both upper arms. Based on the findings of magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography/computed tomography, a diagnosis of malignant soft tissue tumor was strongly suggested. However, further investigation through needle biopsy ultimately led us to the final diagnosis of reactive granuloma. The masses spontaneously resolved after discontinuation of leuprorelin injection. While reactive granulomas after leuprorelin injections are not rare, intramuscular cases are relatively uncommon. Despite using imaging studies as a rational initial approach in the diagnostic process, as we did in our case, their results turned out to be indistinguishable from those of malignant soft tissue tumors, thus highlighting the importance of pathological examination in confirming diagnosis, especially when a patient presents with atypical clinical manifestations.