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El exemestano esta indicado como terapia de segunda linea en CMA en mujeres con posmenopausia natural o inducida, cuya enfermedad ha progresado despues del tratamiento con antiestrogenos solos. El exemestano esta indicado como terapia de tercera linea en mujeres posmenopausicas con CMA, cuya enfermedad ha progresado despues de multiples terapias hormonales. FARMACOCINETICA Y FARMACODINAMIA: Inhibidor esteroideo de la aromatasa, agente antineoplasico: El exemestano es un inactivador esteroideo de la aromatasa, irreversible, relacionado estructuralmente con el sustrato natural androstenediona. En mujeres posmenopausicas, los estrogenos se producen principalmente de la conversion de androgenos a estrogenos a traves de la enzima aromatasa en los tejidos perifericos. La privacion de estrogeno a traves de la inactivacion de la aromatasa es un tratamiento efectivo y selectivo para el cancer de mama dependiente de hormonas en mujeres posmenopausicas. En mujeres posmenopausicas, el exemestano redujo significativamente las concentraciones de estrogeno serico con una dosis inicial de 5 mg, y alcanzando la supresion maxima (> 90%) con dosis de 10-25 mg. En pacientes posmenopausicas con cancer de mama, tratadas con la dosis diaria de 25 mg, la aromatizacion completa del cuerpo se redujo en 98%. El exemestano no posee ninguna actividad progestagenica o estrogenica. Se ha observado una ligera actividad androgenica, probablemente debida a su derivado 17-hidro, principalmente en dosis altas. En estudios de dosis multiples diarias, el exemestano no tuvo efectos detectables sobre la biosintesis suprarrenal del cortisol o la aldosterona, medidos antes o despues de la estimulacion con ACTH, demostrandose asi su selectividad respecto a las otras enzimas involucradas en la via esteroidogenica. Estos datos indican que la terapia de reemplazo con glucocorticoides o mineralocorticoides no es necesaria. Se ha observado un ligero incremento en los niveles sericos de LH y FSH que no es dependiente de la dosis, aun con dosis bajas; este efecto es, sin embargo, el esperado para la clase farmacologica, y es probablemente el resultado de la retroalimentacion a nivel de la pituitaria, debido a la reduccion en los niveles de estrogeno que estimulan la secrecion de gonadotropinas en la pituitaria en mujeres posmenopausicas. Tratamiento coadyuvante del cancer de mama en estadios iniciales: En un estudio multicentrico, aleatorizado, doble ciego, realizado en 4,724 pacientes posmenopausicas con cancer de mama y receptor estrogenico positivo o desconocido, que habian permanecido sin la enfermedad, despues de recibir tratamiento coadyuvante con tamoxifeno durante 2 o 3 anos, fueron aleatorizadas para recibir exemestano (25 mg/dia) o tamoxifeno (20 o 30 mg/dia) durante 2 a 3 anos, hasta completar un total de 5 anos de terapia hormonal. Seguimiento medio de 35 meses: Despues de una duracion media del tratamiento de unos 27 meses y un seguimiento medio de aproximadamente 35 meses, los resultados mostraron que el tratamiento secuencial con exemestano despues de 2 a 3 anos de tratamiento coadyuvante con tamoxifeno, se asocio con una mejoria clinica y estadisticamente significativa en la supervivencia sin enfermedad (DFS) en comparacion con la continuacion del tratamiento con tamoxifeno. El analisis mostro que durante el periodo de estudio, el exemestano redujo el riesgo recidivante del cancer de mama 31% en comparacion con el tamoxifeno (indice de riesgo 0. El efecto benefico del exemestano sobre el tamoxifeno respecto a la DFS fue claro, independientemente del estado ganglionar o de una quimioterapia previa. De igual forma, el exemestano produjo una reduccion significativa del riesgo de cancer de mama contralateral (indice de riesgo 0. Mediana de seguimiento a 52 meses: Despues de una mediana de duracion de tratamiento de 30 meses y una mediana de seguimiento de aproximadamente 52 meses, los resultados mostraron que el tratamiento secuencial con exemestano despues de 2 a 3 anos de tratamiento adyuvante con tamoxifeno, se asocio con una mejoria clinica y estadisticamente significativa de la supervivencia libre de enfermedad en comparacion con la continuacion del tratamiento con tamoxifeno. El analisis mostro que mas alla del periodo de estudio, el exemestano redujo el riesgo de recurrencia de cancer de mama 24% en comparacion con el tamoxifeno (indice de riesgo 0. El efecto benefico de exemestano sobre el tamoxifeno respecto a la supervivencia libre de enfermedad, fue aparentemente independiente del estado ganglionar o de una quimioterapia previa. De igual forma, el exemestano produjo una reduccion significativa del riesgo de cancer de mama contralateral (indice de riesgo 0. Resultados de un subestudio endometrial indicaron que despues de 2 anos de tratamiento hubo una mediana de reduccion en el grosor endometrial de 33% en los pacientes tratados con exemestano en comparacion con una no notable variacion en los pacientes tratados con tamoxifeno. El engrosamiento endometrial, reportado al inicio del tratamiento de estudio, revirtio a la normalidad en 54% de los pacientes tratados con exemestano, buy nandrobol 375 mg injectable steroids deca durabolin, deca. Tratamiento del cancer de mama avanzado: En un estudio clinico, fase 3 realizado por la EORTC (Organizacion Europea para la Investigacion y Tratamiento del Cancer), el exemestano se comparo con el tamoxifeno como tratamiento de primera linea del cancer de mama avanzado. Los resultados indicaron que los pacientes en el grupo de tratamiento del exemestano presentaron una media mayor del tiempo de Supervivencia Sin Progresion (PFS), en comparacion con el tamoxifeno (9.
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