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      ¿Se ha de asumir el efecto de clase farmacológica entre los diferentes análogos de la hormona liberadora de la hormona luteinizante usados en el tratamiento del carcinoma de próstata? Translated title: Does the pharmacological class effect between the different luteinizing hormone releasing hormone analogues used in the treatment of prostate cancer have to be assumed?

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          Abstract

          Introducción: La introducción de la medicina basada en la evidencia está transformando la práctica clínica habitual. Objetivos: Con el enfoque de la medicina basada en la evidencia nos planteamos estudiar si los análogos de la hormona liberadora de la hormona luteinizante son fármacos de una misma clase farmacológica, es decir, si tienen el mismo efecto clínico. Material y métodos: Se ha empleado PubMed como fuente principal de búsqueda. Se revisó la evidencia sobre el supuesto efecto de clase entre análogos y el respaldo bibliográfico existente para su uso en las distintas indicaciones médicas. Cada conclusión se apoya en un nivel de evidencia y grado de recomendación siguiendo las pautas de las «Scottish Intercollegiate Guidelines Network». Resultados: No existen estudios que intenten contestar a la cuestión del efecto de clase entre los análogos o agonistas de la hormona liberadora de la hormona luteinizante. Sí existen revisiones y metaanálisis en cuestiones sobre el manejo terapéutico con análogos, solos o en combinación con la cirugía y la radioterapia. Las comparaciones directas no permiten extraer conclusiones definitivas. Se extraen evidencias indirectas de los ensayos aleatorizados en los que se compara a los diferentes análogos con otros tratamientos para obtener la deprivación androgénica. También se valoran otros factores relacionados con la farmacocinética y la farmacodinámica que puedan apoyar o rechazar la existencia del efecto de clase. Conclusiones: En la actualidad la evidencia científica no es suficiente para respaldar un supuesto efecto de clase farmacológica entre los diferentes análogos en el tratamiento del carcinoma de próstata.

          Translated abstract

          Introduction: Evidence-based medicine is transforming clinical practice because of its progressive implantation. Objectives: We considered studying whether LHRH analogues are agents of the same pharmacological class, i.e., whether they have the same clinical effect, using the approach to evidence-based medicine. Material and methods: PubMed was used as the main source of search. We have reviewed the evidence on the alleged «drug class effect» between analogues and the existing bibliographic support for their use in various medical indications. An evidence level and degree of recommendation have been assigned to each conclusion based on the «Scottish Intercollegiate Guidelines Network». Results: There are no studies designed to answer the question of a class effect between LHRH analogues or agonists. Reviews and meta-analyses have been performed on many other issues related to therapeutic management either with analogues, alone or in combination with surgery or radiation therapy. Direct comparisons do not allow for obtain definitive conclusions. Indirect evidence is obtained from randomized studies comparing the different LHRH analogues to other treatments used to obtain androgen deprivation. Other issues related to pharmacokinetics and pharmacodynamics supporting either the existence or non-existence of class effect were evaluated. Conclusions: The current available evidence is not enough to support a presumed «drug class effect» among the various analogues in the treatment of prostate carcinoma.

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          Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial.

          We did a randomised phase III trial comparing external irradiation alone and external irradiation combined with an analogue of luteinising-hormone releasing hormone (LHRH) to investigate the added value of long-term androgen suppression in locally advanced prostate cancer. Between 1987 and 1995, 415 patients were randomly assigned radiotherapy alone or radiotherapy plus immediate androgen suppression. Eligible patients had T1-2 tumours of WHO grade 3 or T3-4 N0-1 M0 tumours; the median age of participants was 71 years (range 51-80). In both treatment groups, 50 Gy radiation was delivered to the pelvis over 5 weeks, and 20 Gy over 2 weeks as a prostatic boost. Goserelin (3.6 mg subcutaneously every 4 weeks) was started on the first day of irradiation and continued for 3 years; cyproterone acetate (150 mg orally) was given for 1 month starting 1 week before the first goserelin injection. The primary endpoint was clinical disease-free survival. Analyses were by intention to treat. 412 patients had evaluable data, with median follow-up of 66 months (range 1-126). 5-year clinical disease-free survival was 40% (95% CI 32-48) in the radiotherapy-alone group and 74% (67-81) in the combined-treatment group (p=0.0001). 5-year overall survival was 62% (52-72) and 78% (72-84), respectively (p=0.0002) and 5-year specific survival 79% (72-86) and 94% (90-98). Immediate androgen suppression with an LHRH analogue given during and for 3 years after external irradiation improves disease-free and overall survival of patients with locally advanced prostate cancer.
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            Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31.

            Radiation Therapy Oncology Group protocol 85-31 was designed to evaluate the effectiveness of adjuvant androgen suppression, using goserelin, in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy (RT). Eligible patients were those with palpable primary tumor extending beyond the prostate (clinical Stage T3) or those with regional lymphatic involvement. Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and/or seminal vesicle involvement was documented histologically. Stratification was based on histologic differentiation, nodal status, acid phosphatase status, and prior prostatectomy. The patients were randomized to either RT and adjuvant goserelin (Arm I) or RT alone followed by observation and application of goserelin at relapse (Arm II). In Arm I, the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression. Between 1987 and 1992, when the study was closed, 977 patients were entered: 488 to Arm I and 489 to Arm II. As of July 2003, the median follow-up for all patients was 7.6 years and for living patients was 11 years. At 10 years, the absolute survival rate was significantly greater for the adjuvant arm than for the control arm: 49% vs. 39%, respectively (p = 0.002). The 10-year local failure rate for the adjuvant arm was 23% vs. 38% for the control arm (p <0.0001). The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24% vs. 39% (p <0.001) and 16% vs. 22% (p = 0.0052), respectively, both in favor of the adjuvant arm. In a population of patients with unfavorable prognosis carcinoma of the prostate, androgen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival. The improvement in survival appeared preferentially in patients with a Gleason score of 7-10.
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              Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610.

              Radiation Therapy Oncology Group (RTOG) 8610 was the first phase III randomized trial to evaluate neoadjuvant androgen deprivation therapy (ADT) in combination with external-beam radiotherapy (EBRT) in men with locally advanced prostate cancer. This report summarizes long-term follow-up results. Between 1987 and 1991, 456 assessable patients (median age, 70 years) were enrolled. Eligible patients had bulky (5 x 5 cm) tumors (T2-4) with or without pelvic lymph node involvement according to the 1988 American Joint Committee on Cancer TNM staging system. Patients received combined ADT that consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg tid for 2 months before and concurrent with EBRT, or they received EBRT alone. Study end points included overall survival (OS), disease-specific mortality (DSM), distant metastasis (DM), disease-free survival (DFS), and biochemical failure (BF). Ten-year OS estimates (43% v 34%) and median survival times (8.7 v 7.3 years) favored ADT and EBRT, respectively; however, these differences did not reach statistical significance (P = .12). There was a statistically significant improvement in 10-year DSM (23% v 36%; P = .01), DM (35% v 47%; P = .006), DFS (11% v 3%; P < .0001), and BF (65% v 80%; P < .0001) with the addition of ADT, but no differences were observed in the risk of fatal cardiac events. The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinically meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events.
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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Role: ND
                Journal
                aue
                Actas Urológicas Españolas
                Actas Urol Esp
                Asociación Española de Urología (, , Spain )
                0210-4806
                October 2010
                : 34
                : 9
                : 749-757
                Affiliations
                [02] Barcelona orgnameHospital General Vall d'Hebrón orgdiv1Servicio de Oncología Radioterápica España
                [01] orgnameInstituto de Medicina Oncológica y Molecular de Asturias orgdiv1Unidad de Oncología Radioterápica España
                [03] Albacete orgnameComplejo Hospitalario Universitario de Albacete orgdiv1Servicio de Oncología Radioterápica España
                Article
                S0210-48062010000900002
                10.1016/j.acuro.2010.05.013
                c72432a4-836d-4501-ac48-12d28b1e7f08

                This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

                History
                : 24 May 2010
                : 29 March 2010
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 63, Pages: 9
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                Análogos de la hormona liberadora de la hormona luteinizante,Carcinoma prostático,Carcinoma de próstata,Efecto de clase farmacológica,Deprivación androgénica,Medicina basada en la evidencia,Luteinizing hormone releasing hormone analogues,Prostate carcinoma,Carcinoma of the prostate,Drugg class effect,Androgen deprivation,Evidence-based medicine

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