Gignac Gretchen A, Morris Michael J, Hussain Maha
Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
J Urol. 2007 Sep;178(3 Pt 2):S30-5. doi: 10.1016/j.juro.2007.04.033. Epub 2007 Jul 20.
With the wide use of prostate specific antigen to detect response and disease progression resistance to androgen deprivation is being detected at an increasingly earlier stage. We focused on the current management and novel investigational strategies for the chemonaïve patient population with castration resistant metastatic disease.
We reviewed standard and investigational hormonal, chemotherapeutic, biological and immune based strategies for patients with castration resistant metastatic prostate cancer who have not yet received taxane based chemotherapy.
Our understanding of the natural history of this group of patients is evolving. A variety of standard and experimental treatment options are available for this group of patients. Manipulating the androgen receptor signaling axis, targeting antiapoptotic pathways, using antiangiogenic strategies, harnessing the immune system and optimizing docetaxel based regimens and novel cytotoxic agents are under investigation.
Multiple agents currently under development offer a promise of palliation and prolongation of survival above and beyond that of docetaxel. In the absence of guidance from randomized trials with regard to chemotherapy timing, and considering the modest effects of docetaxel on survival, decisions regarding choice of therapy (standard chemotherapy or experimental therapies) must be based on careful consideration of the functional status of each individual, presence of symptoms, comorbidities and overall therapeutic objectives.
随着前列腺特异性抗原在检测反应和疾病进展方面的广泛应用，对雄激素剥夺的耐药性在越来越早的阶段被检测出来。我们关注的是初治的去势抵抗性转移性疾病患者群体的当前治疗管理及新的研究策略。
我们回顾了尚未接受基于紫杉烷化疗的去势抵抗性转移性前列腺癌患者的标准及研究性激素、化疗、生物和免疫治疗策略。
我们对这组患者自然病史的理解正在不断发展。针对这组患者有多种标准和实验性治疗选择。对雄激素受体信号轴的操控、靶向抗凋亡途径、使用抗血管生成策略、利用免疫系统以及优化基于多西他赛的治疗方案和新型细胞毒性药物等正在研究中。
目前正在研发的多种药物有望实现姑息治疗并延长生存期，超越多西他赛的效果。在缺乏关于化疗时机的随机试验指导且考虑到多西他赛对生存期影响有限的情况下，关于治疗选择（标准化疗或实验性治疗）的决策必须基于对每个患者功能状态、症状、合并症及总体治疗目标的仔细考量。
