PURPOSE OF REVIEW: The treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) has significantly changed in the recent years. We provide an updated summary of the new therapeutic agents in this disease and discuss open questions and future challenges. RECENT FINDINGS: mCRPC is now known to frequently retain sensitivity to hormonal manipulation even after the development of castration resistance, and both the androgen synthesis inhibitor abiraterone and the androgen-receptor antagonist enzalutamide have recently shown to prolong survival in mCRPC patients after chemotherapy. Cabazitaxel, a new-generation antitubulin chemotherapeutic, and the radionuclide radium-223 chloride have also been shown to prolong survival. The biological agent cabozantinib, an orally bioavailable tyrosine kinase inhibitor with activity against Met and vascular endothelial growth factor receptor 2, demonstrated promising results in a phase II trial and is currently being assessed in two large randomized phase 3 controlled trials. SUMMARY: This recent progress is unprecedented and has already translated to a significant increase in the available armamentarium of drugs for mCRPC. Nonetheless, there are still significant unresolved questions as to the proper sequencing of these novel drugs along the disease continuum. Moreover, the problem of drug resistance, either primary of acquired, continues to be a major therapeutic obstacle.
PURPOSE OF REVIEW: The treatment landscape in metastatic castration-resistant prostate cancer (mCRPC) has significantly changed in the recent years. We provide an updated summary of the new therapeutic agents in this disease and discuss open questions and future challenges. RECENT FINDINGS: mCRPC is now known to frequently retain sensitivity to hormonal manipulation even after the development of castration resistance, and both the androgen synthesis inhibitor abiraterone and the androgen-receptor antagonist enzalutamide have recently shown to prolong survival in mCRPC patients after chemotherapy. Cabazitaxel, a new-generation antitubulin chemotherapeutic, and the radionuclideradium-223 chloride have also been shown to prolong survival. The biological agent cabozantinib, an orally bioavailable tyrosine kinase inhibitor with activity against Met and vascular endothelial growth factor receptor 2, demonstrated promising results in a phase II trial and is currently being assessed in two large randomized phase 3 controlled trials. SUMMARY: This recent progress is unprecedented and has already translated to a significant increase in the available armamentarium of drugs for mCRPC. Nonetheless, there are still significant unresolved questions as to the proper sequencing of these novel drugs along the disease continuum. Moreover, the problem of drug resistance, either primary of acquired, continues to be a major therapeutic obstacle.
Authors: Daniel P Petrylak; Jitendra G Gandhi; William R Clark; Elisabeth Heath; Jianqing Lin; William K Oh; David B Agus; Bradley Carthon; Susan Moran; Ning Kong; Ajit Suri; Michael Bargfrede; Glenn Liu Journal: Invest New Drugs Date: 2015-01-04 Impact factor: 3.850
Authors: K D M Nakamura; T M Tilli; J L Wanderley; A Palumbo; R M Mattos; A C Ferreira; C E Klumb; L E Nasciutti; E R Gimba Journal: Tumour Biol Date: 2015-09-24
Authors: Anna Solini; Vittorio Simeon; Lisa Derosa; Paola Orlandi; Chiara Rossi; Andrea Fontana; Luca Galli; Teresa Di Desidero; Anna Fioravanti; Sara Lucchesi; Luigi Coltelli; Laura Ginocchi; Giacomo Allegrini; Romano Danesi; Alfredo Falcone; Guido Bocci Journal: Oncotarget Date: 2015-10-06