ESTADO ACTUAL DE LOS AGENTES HORMONALES, QUIMIOTERAPIA Y AGENTES EN INVESTIGACION PARA EL TRATAMIENTO DEL CANCER DE ENDOMETRIO

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El mayor conocimiento de los eventos que provocan la transformación celular y el crecimiento e invasión tumorales permitirá el diseño racional de drogas oncológicas que actúen sobre blancos moleculares específicos.
elit.jpg Autor:
Laurie Elit
Columnista Experto de SIIC
Artículos publicados por Laurie Elit
Coautor
Hal Hirte* 
MD, FRCP(c). McMaster Univesity*
Recepción del artículo
15 de Marzo, 2004
Aprobación
16 de Abril, 2004
Primera edición
3 de Septiembre, 2004
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
Introducción: La mediana de supervivencia de las mujeres con cáncer endometrial avanzado o recurrente es menor que un año. Sólo la mitad de las mujeres con estadios tempranos de cáncer endometrial y factores pronósticos débiles, como alto grado o invasión miometrial profunda, sobrevivirán cinco años. Se han dado increíbles pasos a lo largo de la última década en cuanto a la evaluación de una terapia sistémica para esta enfermedad. Sin embargo, las tasas de supervivencia son aún magras. Métodos: Se llevó a cabo una búsqueda en la literatura mediante Cancerlit, Embase, Medline, Investigational Drug Database (Current Drug Ltd.) y R&D Focus (c IMSworld Publications). Se exploraron también las referencias de los artículos. Los términos de la búsqueda incluyeron: cáncer endometrial, quimioterapia, terapias endocrina/hormonal, biología molecular y nombres específicos de drogas. Revisión: La terapia progestacional ofrece tasas de respuesta de 10% a 20% y de supervivencia menor que un año. Los progestágenos son más efectivos en mujeres con tumores bien diferenciados e intervalos libres de enfermedad prolongados. No existe un papel para la terapia progestacional adyuvante en la enfermedad con estadios tempranos. La quimioterapia con agentes únicos con mayor actividad incluye ifosfamida, cisplatino/carboplatino, doxorrubicina, paclitaxel y topotecán. La quimioterapia combinada provee tasas de respuesta de 40% a 60%; sin embargo, la mediana de supervivencia es todavía hoy menor que un año. Las nuevas áreas de investigación incluyen la identificación y evaluación de nuevas terapias endocrinas activas (por ejemplo, LY353381, HCL y letrozol), quimioterapéuticos (por ejemplo, trastuzumab), la evaluación de agentes quimioterapéuticos en combinación (por ejemplo, paclitaxel, doxorrubicina y platino), además de radiación o en reemplazo de ella. Existen nuevos métodos en desarrollo que involucran moléculas específicas y las vías responsables de la iniciación y crecimiento del carcinoma endometrial, que incluyen: genes supresores tumorales, genes reparadores de discordancias del ADN, oncogenes, moléculas involucradas en la adhesión, invasión y angiogénesis. Conclusión: Es poco probable que se produzcan avances significativos en cuanto a radioterapia, terapia hormonal y quimioterapia. Ciertos avances promisorios respecto de la comprensión de las moléculas involucradas en el desarrollo tumoral y las metástasis permitirán el desarrollo de inhibidores específicos selectivos.

Palabras clave
Cáncer endometrial, quimioterapia, terapia biológica


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Abstract
Introduction: The median survival of women with advanced or recurrent endometrial is less than one year. Only half of the women with early stage endometrial cancer and poor prognostic factors like high grade or deep myometrial invasion will survive 5 years. Over the last decade, incredible strides have been taken in evaluating systemic therapy for this disease. However, survival rates remain poor. Methods: A literature search was conducted using Cancerlit, Embase, Medline, Investigational Drug database (Current Drug Ltd.) and R&D Focus (c IMSworld Publications). The references of the articles were also explored. Search terms included: endometrial cancer, chemotherapy, endocrine/hormonal therapies, molecular biologics, and specific drug names. Review: Progestin therapy offers a 10%-20% response rate and survival of less than 1 year. Progestins are most effective in women with well-differentiated tumors and long disease free interval. There is no role for adjuvant progestin therapy in early stage disease. Single agent chemotherapy with most activity include ifosfamide, cisplatin/carboplatin, doxorubicin, paclitaxel and topotecan. Combination chemotherapy provides response rate of 40%-60%, however, median survival is still less than a year. New areas of research include the identification and evaluation of new active endocrine therapies (i.e., LY353381.HCl and letrozole), chemotherapeutics (i.e., trastuzumab), evaluating chemotherapeutic agents in combination (i.e., paclitaxel, doxorubicin and platinum), in addition to radiation or instead of radiation. New avenues under development involve the specific molecules and pathways responsible for the initiation and growth of endometrial carcinoma including: tumor suppressor genes, DNA mismatch repair genes, oncogenes, molecules involved in adhesion and invasion and angiogenesis. Conclusion: Further significant advanced in radiotherapy, hormonal therapy and chemotherapy are unlikely. Exciting developments in understanding the molecules involved in tumor development and metastasis will allow the development of specific and selective inhibitors.


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Especialidades
Principal: Obstetricia y Ginecología, Oncología
Relacionadas: Anatomía Patológica, Endocrinología y Metabolismo, Farmacología, Medicina Nuclear



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