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The first drug shown to extend life after docetaxel has stopped working. Cabazitaxel, a taxane designed to get past the pumps that expel docetaxel from resistant cells, added about two and a half months, at the cost of a high rate of low white cell counts.
Johann de Bono and the TROPIC investigators randomised 755 men whose metastatic castration-resistant prostate cancer had progressed during or after docetaxel to cabazitaxel or mitoxantrone, each with 10 mg of oral prednisone daily. It was an open-label phase 3 trial with overall survival as the primary endpoint.
Before TROPIC there was nothing after docetaxel. The trial opened the second line and, in the same period as abiraterone and enzalutamide, turned castration-resistant prostate cancer from a single-treatment disease into a sequencing problem. The toxicity is the reason cabazitaxel is used carefully: 82 percent of patients had grade 3 or higher neutropenia and 8 percent had febrile neutropenia, which is why growth factor support became routine.
Proof that a cancer resistant to one taxane is not resistant to all of them, and the beginning of treatment sequencing in castration-resistant disease. The CARD trial later showed that after an androgen receptor drug has failed, cabazitaxel beats switching to the other androgen receptor drug.
This is the paper Europe PMC returns for registry id NCT03392428 with the most citations, so it is the natural first reading for anyone following the TheraP trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.
The end of therapeutic nihilism in castration-resistant prostate cancer. It is also the trial that set the field's expectation of what a positive result looks like in this disease: a hazard ratio near 0.75 and a median gain measured in months, not years.
Shares TAX 327: docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer, Mitoxantrone, Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs, Prednisone and the tag prostate-evidence.
Shares AFFIRM: increased survival with enzalutamide in prostate cancer after chemotherapy, Johann de Bono, 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 Randomise the order of treatment, not only the drugs: a strategy platform for metastatic prostate cancer, 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 Johann de Bono, 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, Acquired resistance to every therapy, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.
Shares AFFIRM: increased survival with enzalutamide in prostate cancer after chemotherapy, 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 Johann de Bono, 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, Docetaxel, Metastatic castration-resistant prostate cancer 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, Acquired resistance to every therapy, Metastatic castration-resistant prostate cancer and the tag prostate-evidence.