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Prostate cancer adapts to having almost no testosterone. This trial did the opposite of what the textbook says and gave men large doses of testosterone. Three in ten responded, and more than half responded again to the hormone-blocking drug that had stopped working.
Benjamin Teply, Samuel Denmeade and colleagues at Johns Hopkins gave monthly intramuscular testosterone cipionate 400 mg, on top of continued luteinising hormone-releasing hormone agonist therapy, to 30 asymptomatic men whose metastatic castration-resistant prostate cancer had progressed on enzalutamide. Rapid cycling between high and low serum testosterone is called bipolar androgen therapy.
The rationale is the same adaptation described by Visakorpi and Chen. A cell that has upregulated the androgen receptor to survive castration is, on that account, vulnerable to a flood of ligand. The co-primary endpoints were the proportion with a 50 percent fall in prostate-specific antigen on bipolar androgen therapy and on enzalutamide rechallenge afterwards, and both were met. It is the resensitisation result, not the direct response rate, that makes the approach interesting.
A demonstration that a drug that has stopped working can be made to work again by changing the environment the tumour has adapted to, rather than by changing the drug. It is the strongest clinical evidence in prostate cancer for treating resistance as something reversible.
Shares Molecular determinants of resistance to antiandrogen therapy, Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, PSA (prostate-specific antigen), Enzalutamide and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, Take high-dose testosterone to phase 3, with progression-free survival through the second line as the primary endpoint, 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 PSA (prostate-specific antigen), Too many combinations to test, Enzalutamide, Castration-resistant prostate cancer (CRPC) and the tag prostate-evidence.
Shares Molecular determinants of resistance to antiandrogen therapy, PSA (prostate-specific antigen), Enzalutamide, 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 Rotate between drugs on a fixed schedule instead of waiting for failure, TRANSFORMER: bipolar androgen therapy versus enzalutamide in asymptomatic metastatic castration-resistant prostate cancer, Bipolar androgen therapy (BAT), Too many combinations to test and the tag prostate-evidence.
Shares 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, Acquired resistance to every therapy and the tag prostate-evidence.
Shares 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, Acquired resistance to every therapy and the tag prostate-evidence.