Download Nuevos conceptos y alternativas en el tratamiento hormonal

Nuevos conceptos y
alternativas en el
tratamiento
hormonal para la
enfermedad
avanzada
María J. Ribal
Servicio de Urología.
Hospital Clínic. Universitat de Barcelona
• 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.
•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
Tratamiento inmediato o diferido
Selection Criteria
Results Intermittent versus Continous AD
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
Castración resistencia
Prostate Cancer Continuum
Locally Advanced
Monotherapy
Multimodality
Mets Asymptomatic
Hormone Naive
Rising PSA
Hormone Naive
Rising PSA
CRPC
Mets Asymptomatic CRPC
Mets CRPC Symptomatic
CRPC Post-Docetaxel
Death From CRPC
NCCN, 2010.
•
•
Análisis secundario de la rama placebo de un estudio RCT (atrasentran vs placebo)
N = 470 pts afectos CPRC M0
Time (mo)
•
Median time to disease progression
22.4
Median time to first bone metastasis
25.2
Median overall survival
46.8
Análisis multivariante:
Predictive factors for
outcome*
Factor not predictive
for outcome*
PSA
BMI
PSA velocity
Charles B. Huggins
“Despite regressions of great magnitude,
it is obvious that there are many
failures of endocrine therapy to control
the disease.”
CRPC: Adaptation or selection?
Androgen-sensitive tumour cells
Androgen-independent tumour cells
Adaptation theory: genetic changes provide survival mechanisms that allow the
cells to continue growing in the androgen depleted environment
Hormone
withdrawal
Tumour hormonedependent
Regression of
tumour
Hormonewithdrawal
Clonal selection pathway, androgen
withdrawal allows for the selection of androgenindependent cells to proliferate that existed at the time of
initiation of therapy
Tumour
hormoneindependent
AR with DHT
Ligand (Dimers)
Testosterone
5a-R
DHT
Activated AR gets in the
nucleus and binds DNA
Hsp 70
RA (Inactive)
Hsp 90
Gene expression
Androgen Response
Element (ARE)