Department of Urology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
BJU Int. 2012 Dec;110(11 Pt B):E635-40. doi: 10.1111/j.1464-410X.2012.11364.x. Epub 2012 Aug 13.
Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Docetaxel rechallenge has shown preserved anti-tumour activity and has therefore been proposed as an option for further treatment in patients with metastatic castration-resistant prostate cancer, who have shown a good response to first-line chemotherapy with docetaxel. The present study provides evidence of docetaxel activity in patients who were treated with full-dose (75 mg/m(2) ) 3-weekly docetaxel at first-line chemotherapy and rechallenge. It shows that PSA response to first-line chemotherapy may provide a rational indication for docetaxel rechallenge.
• To determine whether prostate-specific antigen (PSA) response at first-line chemotherapy with docetaxel correlates with PSA response and survival at docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC).
• We retrospectively evaluated the oncological outcomes of patients with mCRPC, who were treated with full-dose (75 mg/m(2) ), 3-weekly docetaxel plus prednisone/prednisolone at first-line chemotherapy and rechallenge, between 1999 and 2011, at our institution. • The endpoints were PSA-progression-free survival (PSA-PFS) and overall survival (OS) at docetaxel rechallenge. • Statistical analyses included Kaplan-Meier curves and log-rank tests to evaluate the effect of PSA response at first-line chemotherapy on PSA-PFS and OS at rechallenge.
• Fourty-four patients were included in the analysis. • At a median (range) follow-up of 26.4 (9.8-89.8) months after the first administration of docetaxel, 24 (55%) patients had died. At first-line chemotherapy, 36 (82%) patients achieved a reduction in PSA level of ≥50%. At rechallenge, 10 (28%) patients responded with a reduction of ≥50% for a second time. • The median (95% confidence interval [CI]) PSA-PFS was 5.9 (95% CI 3.5-6.8) months and the median OS was 21.8 (95% CI 19.9-23.7) months at docetaxel rechallenge. • Of the PSA response variables evaluated, only a PSA level reduction of ≥50% at first-line chemotherapy correlated significantly with prolonged PSA-PFS (5.8 vs. 4.5 months; P= 0.01) and OS (22.1 vs. 7.2 months; P= 0.03) at rechallenge.
• In the present single-institution study, a reduction in PSA level of ≥50% at first-line chemotherapy with docetaxel correlated with superior PSA-PFS and OS in the rechallenge setting and might, therefore, present a rational indication for docetaxel rechallenge.
研究类型-治疗（病例系列）证据水平 4 已知内容：多西他赛再挑战显示出保留的抗肿瘤活性，因此被提议作为转移性去势抵抗性前列腺癌患者一线化疗后进一步治疗的选择，这些患者在一线化疗中对多西他赛表现出良好的反应。本研究提供了在一线化疗中接受全剂量（75mg/m2）3 周多西他赛治疗并再挑战的患者中多西他赛活性的证据。它表明，前列腺特异性抗原（PSA）对一线化疗的反应可能为多西他赛再挑战提供合理的指征。
•确定转移性去势抵抗性前列腺癌（mCRPC）患者一线化疗中多西他赛的 PSA 反应是否与 PSA 反应和再挑战时的生存相关。
•我们回顾性评估了在我们机构接受全剂量（75mg/m2）3 周多西他赛联合泼尼松/强的松一线化疗和再挑战的 mCRPC 患者的肿瘤学结局，时间范围为 1999 年至 2011 年。•终点是 PSA 无进展生存期（PSA-PFS）和总生存期（OS）在多西他赛再挑战时。•统计分析包括 Kaplan-Meier 曲线和对数秩检验，以评估 PSA 反应在一线化疗对再挑战时 PSA-PFS 和 OS 的影响。
•44 例患者纳入分析。•在多西他赛首次给药后中位数（范围）随访 26.4（9.8-89.8）个月时，24 例（55%）患者死亡。在一线化疗中，36 例（82%）患者 PSA 水平降低≥50%。在再挑战时，10 例（28%）患者第二次 PSA 下降≥50%。•多西他赛再挑战时 PSA-PFS 的中位数（95%置信区间[CI]）为 5.9（95%CI 3.5-6.8）个月，OS 中位数（95%CI）为 21.8（95%CI 19.9-23.7）个月。•在评估的 PSA 反应变量中，只有一线化疗时 PSA 水平降低≥50%与 PSA-PFS（5.8 与 4.5 个月；P=0.01）和 OS（22.1 与 7.2 个月；P=0.03）的延长显著相关。
•在本单中心研究中，一线化疗时 PSA 水平降低≥50%与 PSA-PFS 和 OS 改善相关，因此可能为多西他赛再挑战提供合理的指征。
