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Nuevos conceptos y alternativas en el tratamiento hormonal para la enfermedad avanzada

Nuevos conceptos y alternativas en el tratamiento hormonal para la enfermedad avanzada. María J. Ribal Servicio de Urología. Hospital Clínic. Universitat de Barcelona.

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Nuevos conceptos y alternativas en el tratamiento hormonal para la enfermedad avanzada

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  1. Nuevos conceptos y alternativas en el tratamiento hormonal para la enfermedad avanzada María J. Ribal Servicio de Urología. Hospital Clínic. Universitat de Barcelona

  2. El tratamiento hormonal no está exento de efectos secundarios, debemos tener en cuenta la calidad de vida de nuestros pacientes. • Podemos retrasar la castración-resistencia? • Tratamiento hormonal intermitente • Tratamiento hormonal diferido • Los mecanismos moleculares de desarrollo del CPCR han abierto las puertas a nuevas alternativas terapéuticas. • El RA es uno de los efectivos en el desarrollo del CPCR. • Las maniobras hormonales siguen siendo vigentes en el CPCR.

  3. We performed a matched cohort study using linked administrative data at the Institute for Clinical Evaluative Sciences (ICES) in Ontario, Canada (population of approximately 11,000,000). • Men with prostate cancer were identified using the Ontario Cancer Registry (OCR). The OCR is a comprehensive provincial registry that captures more than 95% of cancer cases

  4. Tratamiento inmediato o diferido

  5. Selection Criteria

  6. Results Intermittent versus Continous AD

  7. Dynamics of bone mineral density (BMD) during intermittent ADT (ASCO#4558) • Prospective study, N = 48 PCa pts treated with intermittent ADT for biochemical relapse after RP or RT ADT-induced loss of BMD was attenuated during the ‘off treatment’ period of an intermittent ADT regimen, suggesting less net BMD loss than during continuous ADT

  8. Castración resistencia

  9. Prostate Cancer Continuum Locally Advanced Monotherapy Multimodality Mets Asymptomatic Hormone Naive Rising PSA Hormone Naive Mets Asymptomatic CRPC Rising PSA CRPC Mets CRPC Symptomatic CRPC Post-Docetaxel Death From CRPC NCCN, 2010.

  10. Análisis secundario de la rama placebo de un estudio RCT (atrasentran vs placebo) N = 470 pts afectos CPRC M0 Análisis multivariante:

  11. Charles B. Huggins • “Despite regressions of great magnitude, it is obvious that there are many failures of endocrine therapy to control the disease.”

  12. CRPC: Adaptation or selection? Adaptation theory: genetic changes provide survival mechanisms that allow the cells to continue growing in the androgen depleted environment Hormone withdrawal Regression of tumour Tumour hormone-dependent Tumour hormone-independent Hormone- withdrawal Clonal selection pathway, androgen withdrawal allows for the selection of androgen-independent cells to proliferate that existed at the time of initiation of therapy Androgen-sensitive tumour cells Androgen-independent tumour cells

  13. AR with DHT Ligand (Dimers) Activated AR gets in the nucleus and binds DNA Gene expression Androgen Response Element (ARE) Testosterone 5a-R DHT Hsp 70 RA (Inactive) Hsp 90

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