Ghashghaei M, Kucharczyk M, Elakshar S, Muanza T, Niazi T
Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, Montreal, QC.
Division of Experimental Medicine, McGill University, Montreal, QC.
Curr Oncol. 2019 Oct;26(5):e640-e650. doi: 10.3747/co.26.5005. Epub 2019 Oct 1.
Prostate cancer (pca) is the most common non-dermatologic cancer and the 3rd leading cause of male cancer mortality in Canada. In patients with high-risk localized or recurrent pca, management typically includes the combination of long-term androgen deprivation therapy (adt) and radiotherapy (rt). New androgen-receptor-axis targeted therapies (arats), which await validation, offer an option to intensify therapy.
In this narrative review, we report the relevant history that has supported combining adt with rt. The literature in PubMed was searched for studies involving pca and novel arats (abiraterone acetate, enzalutamide, apalutamide, darolutamide) published between 1995 and 2019. Literature discussing clinical trials in which those modalities were combined was extracted and synthesized into a combined molecular and clinical discussion. Potential treatment intensification mechanisms and rationales are explored.
Early results from three phase i/ii trials demonstrated that concurrent abiraterone acetate, adt, and rt is safe, improves the extent of chemical castration, and is associated with limited treatment failures. A single study implies synergy for radiosensitization beyond that facilitated by conventional adt. Studies investigating the combination of other arats with rt are under way, including multiple phase iii trials, but short-term results are not yet available.
前列腺癌（pca）是加拿大最常见的非皮肤癌，也是男性癌症死亡的第三大主要原因。对于高危局限性或复发性前列腺癌患者，治疗通常包括长期雄激素剥夺疗法（adt）和放射疗法（rt）的联合应用。有待验证的新型雄激素受体轴靶向疗法（arats）为强化治疗提供了一种选择。
在这篇叙述性综述中，我们报告了支持adt与rt联合应用的相关历史。在PubMed中检索了1995年至2019年间涉及前列腺癌和新型arats（醋酸阿比特龙、恩杂鲁胺、阿帕他胺、达洛鲁胺）的研究。提取并综合了讨论这些治疗方式联合应用的临床试验的文献，形成了分子与临床相结合的讨论。探讨了潜在的治疗强化机制和基本原理。
三项I/II期试验的早期结果表明，醋酸阿比特龙、adt和rt联合应用是安全的，可提高化学去势的程度，且治疗失败情况有限。一项研究表明，其放射增敏作用具有协同效应，超出了传统adt的促进作用。目前正在进行其他arats与rt联合应用的研究，包括多项III期试验，但短期结果尚未可得。
