RESUMO
Clinical trial data forms the foundation of how we treat men with metastatic prostate cancer who are initiating therapy. However, clinical trial data does not answer everything; hence, good clinical practice, pragmatism, and occasionally extrapolation drives how we manage these patients. Fortunately, multiple international guideline committees meet regularly and offer clinical guidance. In this mini-review, we focus on the United States National Comprehensive Cancer Network, European Society for Medical Oncology, and European Association of Urology (EAU) recommendations for the initial treatment of metastatic prostate cancer.
Assuntos
Antagonistas de Androgênios/uso terapêutico , Metástase Neoplásica/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Acetato de Abiraterona/administração & dosagem , Acetato de Abiraterona/efeitos adversos , Acetato de Abiraterona/uso terapêutico , Antagonistas de Androgênios/efeitos adversos , Ensaios Clínicos como Assunto , Docetaxel/administração & dosagem , Docetaxel/efeitos adversos , Docetaxel/uso terapêutico , Humanos , Infusões Intravenosas , Masculino , Oncologia/organização & administração , Metástase Neoplásica/patologia , Guias de Prática Clínica como Assunto , Neoplasias da Próstata/patologia , Neoplasias da Próstata/secundário , Inibidores da Síntese de Esteroides/uso terapêutico , Moduladores de Tubulina/uso terapêutico , Urologia/organização & administraçãoAssuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Hormonais/administração & dosagem , Amplificação de Genes , Calicreínas/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/tratamento farmacológico , Receptores Androgênicos/genética , Testosterona/administração & dosagem , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adenocarcinoma/secundário , Idoso , Androstenos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Masculino , Neoplasias da Próstata/sangue , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-myc/genética , Inibidores da Síntese de Esteroides/uso terapêutico , Resultado do TratamentoRESUMO
The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has been revolutionized by the arrival of multiple novel agents in the past 2 years. Immunotherapy in the form of sipuleucel-T, androgen axis inhibitors, including abiraterone acetate and enzalutamide, a chemotherapeutic agent, cabazitaxel, and a radiopharmaceutical, radium-223, have all yielded incremental extensions of survival and have been recently approved. A number of other agents appear promising in early studies, suggesting that the armamentarium against castrate-resistant prostate cancer is likely to continue to expand. Emerging androgen pathway inhibitors include androgen synthesis inhibitors (TAK700), androgen receptor inhibitors (ARN-509, ODM-201), AR DNA binding domain inhibitors (EPI-001), selective AR downregulators or SARDs (AZD-3514), and agents that inhibit both androgen synthesis and receptor binding (TOK-001/galeterone). Promising immunotherapeutic agents include poxvirus vaccines and CTLA-4 inhibitor (ipilimumab). Biologic agents targeting the molecular drivers of disease are also being investigated as single agents, including cabozantinib (Met and VEGFR2 inhibitor) and tasquinimod (angiogenesis and immune modulatory agent). Despite the disappointing results seen from studies evaluating docetaxel in combination with other agents, including GVAX, anti-angiogentic agents (bevacizumab, aflibercept, lenalinomide), a SRC kinase inhibitor (dasatinib), endothelin receptor antagonists (atrasentan, zibotentan), and high-dose calcitriol (DN-101), the results from the trial evaluating docetaxel in combination with the clusterin antagonist, custirsen, are eagerly awaited. New therapeutic hurdles consist of discovering new targets, understanding resistance mechanisms, the optimal sequencing and combinations of available agents, as well as biomarkers predictive for benefit. Novel agents targeting bone metastases are being developed following the success of zoledronic acid and denosumab. Finally, all of these modalities do not appear curative, suggesting that clinical trial enrollment and a better understanding of biology remain of paramount importance.