Until recently, docetaxel-based therapy represented the only therapy shown to prolong survival in patients with metastatic castration-resistant prostate cancer （mCRPC）. The past year and a half has been marked by un...Until recently, docetaxel-based therapy represented the only therapy shown to prolong survival in patients with metastatic castration-resistant prostate cancer （mCRPC）. The past year and a half has been marked by unprecedented progress in treatments for this disease. Three positive phase III clinical trials have emerged, each evaluating agents （sipuleuceI-T, cabazitaxel and abiraterone） with distinct mechanisms of action. Herein, the three pivotal trials are described alongside both past and current large phase III studies conducted in this mCRPC. The overall survival for patients with mCRPC treated in current clinical trials is considerably longer than noted in the past. We note that more recent trials with older agents have also shown improved survival and discuss potential non-therapeutic biases that influence this critical measure of outcome. The necessity for utilizing randomized trials when evaluating new therapeutics is emphasized given the changing prognosis in this mCRPC.展开更多
In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional ...In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleuceI-T, cabazitaxel, abiraterone, enzalutamide and （most recently） radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer （e.g. samarium-153 and strontium-89）, radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.展开更多
文摘Until recently, docetaxel-based therapy represented the only therapy shown to prolong survival in patients with metastatic castration-resistant prostate cancer （mCRPC）. The past year and a half has been marked by unprecedented progress in treatments for this disease. Three positive phase III clinical trials have emerged, each evaluating agents （sipuleuceI-T, cabazitaxel and abiraterone） with distinct mechanisms of action. Herein, the three pivotal trials are described alongside both past and current large phase III studies conducted in this mCRPC. The overall survival for patients with mCRPC treated in current clinical trials is considerably longer than noted in the past. We note that more recent trials with older agents have also shown improved survival and discuss potential non-therapeutic biases that influence this critical measure of outcome. The necessity for utilizing randomized trials when evaluating new therapeutics is emphasized given the changing prognosis in this mCRPC.
文摘In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer （mCRPC）. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleuceI-T, cabazitaxel, abiraterone, enzalutamide and （most recently） radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer （e.g. samarium-153 and strontium-89）, radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.
