Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, Tor Vergata General Hospital, Rome, Italy.
Unit of Radiation Oncology, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.
Semin Oncol. 2018 Oct;45(5-6):303-315. doi: 10.1053/j.seminoncol.2018.10.001. Epub 2018 Oct 30.
The tumors of many patients with prostate cancer eventually become refractory to androgen deprivation therapy with progression to metastatic castration-resistant disease. Significant advances in the treatment of metastatic castration-resistant prostate cancer (mCRPC) have been made in recent years, and new treatment strategies have recently been made available. The aim of this report was to schematically review all the approved pharmacologic treatment options for patients with mCRPC through 2018, analyzing the efficacy and possible side effects of each therapy to assist clinicians in reaching an appropriate treatment decision. New biomarkers potentially of aid in the choice of treatment in this setting are also briefly reviewed.
We performed a literature search of clinical trials of new drugs and treatments for patients diagnosed with mCRPC published through 2018.
Two new hormonal drugs, abiraterone acetate and enzalutamide have been approved by FDA in 2011 and 2012, respectively for the treatment of patients with mCRPC and have undergone extensive testing. While these treatments have shown a benefit in progression-free and overall survival, the appropriate sequencing must still be determined so that treatment decisions can be made based on their specific clinical profile. Cabazitaxel has been shown to be an efficient therapeutic option in a postdocetaxel setting, while its role in chemotherapy-naïve patients must still be determined. Sipuleucel-T and radium-223 have been studied in patients without visceral metastases and have achieved overall survival benefits with good safety profiles. The feasibility and efficacy of combinations of new treatments with other known therapies such as chemotherapy are currently under investigation.
Drug development efforts continue to attempt to prolong survival and improve quality of life in the mCRPC setting, with several therapeutic options available. Ongoing and future trials are needed to further assess the efficacy and safety of these new drugs and their interactions, along with the most appropriate sequencing.
许多前列腺癌患者的肿瘤最终对雄激素剥夺疗法产生抗药性，进展为转移性去势抵抗性疾病。近年来，转移性去势抵抗性前列腺癌（mCRPC）的治疗取得了重大进展，新的治疗策略最近已经问世。本报告的目的是通过 2018 年对所有批准的 mCRPC 患者的药物治疗选择进行综述，分析每种治疗方法的疗效和可能的副作用，以帮助临床医生做出适当的治疗决策。还简要回顾了在这种情况下可能有助于治疗选择的新生物标志物。
我们对 2018 年之前发表的新药物和治疗 mCRPC 患者的临床试验进行了文献检索。
两种新的激素药物醋酸阿比特龙和恩杂鲁胺分别于 2011 年和 2012 年获得 FDA 批准用于治疗 mCRPC，并且已经进行了广泛的测试。虽然这些治疗方法在无进展生存期和总生存期方面显示出获益，但仍需确定适当的治疗顺序，以便根据其特定的临床特征做出治疗决策。卡巴他赛在多西他赛治疗后显示出有效的治疗选择，但其在化疗初治患者中的作用仍需确定。Sipuleucel-T 和镭-223 已在无内脏转移患者中进行了研究，并具有良好的安全性和总生存期获益。目前正在研究新的治疗方法与其他已知疗法（如化疗）联合应用的可行性和疗效。
药物开发工作继续努力延长 mCRPC 患者的生存期并提高生活质量，目前有多种治疗选择。需要进行正在进行和未来的试验，以进一步评估这些新药的疗效和安全性及其相互作用，以及最合适的治疗顺序。
