Sunnybrook Health Sciences Centre, Odette Cancer Centre, Toronto, Ontario, Canada.
Clin Oncol (R Coll Radiol). 2013 Jul;25(7):406-30. doi: 10.1016/j.clon.2013.03.002. Epub 2013 Apr 12.
Since 2004, docetaxel-based chemotherapy has been the standard of care for men with metastatic castration-resistant prostate cancer (mCRPC), but recently randomised controlled trials (RCTs) of novel agents have shown promise in extending overall survival. These trials have evaluated agents delivered before chemotherapy, to replace or supplement docetaxel, or addressed treatment options for men who have progressed on docetaxel therapy. This review was undertaken to determine which systemic therapies improve cancer- or patient-related outcomes in men with mCRPC.
Searches were carried out in MEDLINE, EMBASE, the Cochrane Library and relevant conference proceedings. Eligible articles included RCTs comparing systemic therapy or combination (excluding primary or secondary androgen deprivation therapy, bone protective agents or radionuclides) with placebo or other agents in men with mCRPC.
Twenty-five RCTs met the selection criteria. In chemotherapy-naive patients, targeted therapy with tasquinimod conferred a benefit in progression-free survival. Immunotherapy with sipuleucel-T extended overall survival and was well tolerated, but had no effect on the time to disease progression. Hypercastration with abiraterone extended progression-free survival, whereas overall survival was improved but not statistically proven. In the chemotherapy setting, updated and new trials of docetaxel alone confirmed the survival benefit seen in previous studies. A survival benefit with the addition of estramustine to docetaxel shown in a previous study did not lead to an improvement in pain palliation or quality of life. Trials of combining targeted therapies with docetaxel generally did not extend survival. The addition of bevacizumab improved progression-free survival, but not overall survival. The addition of GVAX immunotherapy or calcitriol was harmful. In the post-chemotherapy setting, progression-free and overall survival benefits were detected with cabazitaxel, abiraterone and enzalutamide. Cabazitaxel was associated with greater toxicity, whereas abiraterone and enzalutamide had less severe adverse effects. Satraplatin and sunitinib both extended progression-free survival, but did not improve overall survival.
Docetaxel-based chemotherapy remains the standard of care in men with mCRPC who are candidates for palliative systemic therapy. Promising results are emerging with sipuleucel-T and abiraterone in the pre-docetaxel setting and cabazitaxel, abiraterone and enzalutamide in patients who progress on or after docetaxel. Further research to determine the optimal choice, sequence or even the combination of these agents is necessary.
自 2004 年以来，多西他赛为基础的化疗一直是转移性去势抵抗性前列腺癌（mCRPC）患者的标准治疗方法，但最近新型药物的随机对照试验（RCT）显示在延长总生存期方面有希望。这些试验评估了在化疗前给予的药物，以替代或补充多西他赛，或针对接受多西他赛治疗后进展的患者的治疗选择。进行这项综述是为了确定哪些系统治疗方法可以改善 mCRPC 男性的癌症相关或患者相关结局。
在 MEDLINE、EMBASE、Cochrane 图书馆和相关会议记录中进行了检索。符合条件的文章包括比较系统治疗或联合治疗（不包括原发性或继发性去势治疗、骨保护剂或放射性核素）与安慰剂或其他药物在 mCRPC 男性中的 RCT。
25 项 RCT 符合入选标准。在化疗初治患者中，tasquinimod 的靶向治疗可延长无进展生存期。sipuleucel-T 的免疫治疗可延长总生存期，且耐受性良好，但对疾病进展时间无影响。用 abiraterone 进行超去势治疗可延长无进展生存期，而总生存期的改善并未得到统计学证实。在化疗环境中，对多西他赛的更新和新试验证实了先前研究中观察到的生存获益。先前研究显示，多西他赛联合雌莫司汀可改善疼痛缓解或生活质量，但并未导致改善。靶向治疗联合多西他赛的试验一般未能延长生存期。贝伐单抗可改善无进展生存期，但不能改善总生存期。添加 GVAX 免疫治疗或骨化三醇会产生不良影响。在化疗后环境中，cabazitaxel、abiraterone 和 enzalutamide 可检测到无进展生存期和总生存期获益。与 cabazitaxel 相关的毒性更大，而 abiraterone 和 enzalutamide 的不良反应则较轻。satraplatin 和 sunitinib 均可延长无进展生存期，但不能改善总生存期。
对于适合姑息性全身治疗的 mCRPC 男性，多西他赛为基础的化疗仍然是标准治疗方法。在 docetaxel 之前的治疗中，sipuleucel-T 和 abiraterone 以及 cabazitaxel、abiraterone 和 enzalutamide 在 docetaxel 进展或之后的患者中出现了有希望的结果。有必要进一步研究确定这些药物的最佳选择、顺序甚至联合使用。
