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Twenty-one men whose prostate cancer had already stopped responding to every hormone treatment available were given a drug that shuts off the last remaining source of androgen. Two thirds had their PSA fall, which proved the cancer had never stopped depending on the hormone.
Gerhardt Attard, Johann de Bono and colleagues at the Royal Marsden and the Institute of Cancer Research ran the first-in-human study of abiraterone acetate, a selective inhibitor of cytochrome P450 17A1 (CYP17), the enzyme that makes androgen in the adrenal gland and in the tumour itself. Twenty-one chemotherapy-naive men whose disease was resistant to multiple hormonal therapies were dosed through five levels from 250 mg to 2,000 mg.
The result settled a twenty-year argument about what castration-resistant prostate cancer is. If the disease were genuinely hormone-refractory, removing the residual androgen would do nothing. It did a great deal, and the secondary mineralocorticoid excess that the drug produces (hypertension, hypokalaemia, lower-limb oedema) was managed with a mineralocorticoid receptor antagonist, which is why abiraterone is still given with a steroid today.
The proof, in people, that castration-resistant prostate cancer is usually still androgen-driven. It renamed the disease (hormone-refractory became castration-resistant) and it opened the line of drugs that now dominate treatment at every stage from first diagnosis of metastatic disease onwards.
Abiraterone with androgen deprivation is a standard first-line doublet for metastatic hormone-sensitive prostate cancer, consistent with the STAMPEDE result.
One of the most cited trial reports Europe PMC returns for Abiraterone acetate in Prostate cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.
Abiraterone became a standard treatment for metastatic castration-resistant prostate cancer and, after later trials, for hormone-sensitive and high-risk localised disease.
The design specification for the second-generation antiandrogens. A drug for castration-resistant prostate cancer has to stay an antagonist when the receptor is abundant, which is what enzalutamide, apalutamide and darolutamide were engineered to do and what bicalutamide fails to do.
Shares Abiraterone in metastatic prostate cancer without previous chemotherapy, Johann de Bono, PSA (prostate-specific antigen), Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares COU-AA-301: abiraterone and increased survival in metastatic castration-resistant prostate cancer after docetaxel, Molecular determinants of resistance to antiandrogen therapy, PSA (prostate-specific antigen), Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, PSA (prostate-specific antigen), Abiraterone acetate, Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, PSA (prostate-specific antigen), Castration-resistant prostate cancer (CRPC), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, Castration-resistant prostate cancer (CRPC), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch, Androgen receptor and the tag prostate-evidence.
Shares PSA (prostate-specific antigen), Abiraterone acetate, Castration-resistant prostate cancer (CRPC), Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, PSA (prostate-specific antigen), Abiraterone acetate, Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares Johann de Bono, The Institute of Cancer Research, The Royal Marsden, Prostate cancer roadmap: from Huggins and the discovery that a cancer can depend on a hormone, through the PSA epidemic and what it cost, the androgen receptor drugs, the DNA repair subset and PSMA, to a 2032 registry watch and the tag prostate-evidence.