Department of Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA.
Oncologist. 2023 May 8;28(5):392-401. doi: 10.1093/oncolo/oyac279.
Radiopharmaceuticals have been utilized for men with advanced prostate cancer for decades. Older agents, seldom used today, provided palliation for bone metastatic pain. In 2013, the alpha emitter radium-223 provided a catalyst for the field by prolonging survival in men with metastatic castrate-resistant prostate cancer (mCRPC). Recently radioisotopic therapies have gained further interest with the development and FDA approval of 177 lutetium (177Lu)-PSMA-617 (also known as lutetium Lu-177 vipivotide tetraxetan). This agent targets the prostate-specific membrane antigen (PSMA) expressed on the cell surface of prostate cancer cells with a beta-emitting isotope (177Lu). This clinical review summarizes key data reported from 177Lu-PSMA-617 clinical trials, including data from the phase III VISION trial which were pivotal for regulatory approval in heavily pretreated PSMA-PET-positive patients with mCRPC. The current field of radiopharmaceuticals is in a rapid state of flux. Additional phase III trials are now ongoing in patients with mCRPC and in patients with metastatic castrate-sensitive prostate cancer. The results from these potential practice-changing trials are highly anticipated. Earlier phase trials (I/II) are in progress examining combination therapies, radiolabeled monoclonal antibodies, and novel compounds. Studies of PSMA-targeted therapies using both beta emitters such as 177Lu and novel alpha emitters such 225 actinium are in progress. During the next decade, radiopharmaceuticals will likely play a central role in the management of patients with advanced prostate cancer.
放射性药物在治疗晚期前列腺癌方面已有数十年的应用历史。过去使用较少的较老药物可缓解骨转移疼痛。2013 年，α发射体镭-223 通过延长转移性去势抵抗性前列腺癌（mCRPC）患者的生存时间，为该领域提供了催化剂。最近，随着放射性同位素疗法的发展和 FDA 批准 177 镥（177Lu）-PSMA-617（也称为镥 Lu-177 vipivotide tetraxetan），该疗法进一步受到关注。该药物靶向表达在前列腺癌细胞表面的前列腺特异性膜抗原（PSMA），使用β发射同位素（177Lu）。本临床综述总结了来自 177Lu-PSMA-617 临床试验的关键数据，包括来自 III 期 VISION 试验的数据，这些数据对于在 mCRPC 中 PSMA-PET 阳性且预处理较多的患者中获得监管批准至关重要。目前放射性药物领域正在迅速变化。目前正在对 mCRPC 患者和转移性去势敏感型前列腺癌患者进行额外的 III 期临床试验。这些可能改变实践的试验结果备受期待。早期的 I/II 期试验正在进行，以研究联合治疗、放射性标记单克隆抗体和新型化合物。使用β发射体（如 177Lu）和新型α发射体（如 225 锕）的 PSMA 靶向治疗研究正在进行中。在未来十年，放射性药物可能在治疗晚期前列腺癌患者方面发挥核心作用。
