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在芝加哥当地时间5月31日上午的ASCO泌尿生殖肿瘤专场上，Cedars-Sinai医学中心放射肿瘤部的Howard Sandler口头报告了一项针对高危、局部前列腺癌的首个有效辅助化疗的研究（摘要号LBA5002）。医脉通对此进行了报道。
ASCO观点：
“辅助化疗使一些最常见类型肿瘤的患者获得重要的生存获益，现在我们终于在前列腺癌患者中看到了同样的现象。目前我们对这种历史悠久的治疗方法有了新的应用。没有联邦政府资助的临床试验，我们不可能获得今天的进步。”
联邦政府资助的一项III期研究发现，在标准激素治疗和放疗中加入多西他赛化疗可降低高危、局部前列腺癌患者的死亡风险。在平均随访时间5.5年时，标准方案治疗组和多西他赛化疗组的四年总存活率分别为89%和93%。
据作者报道，在美国每年有高达33000的人诊断为高危、局部前列腺癌。
洛杉矶Cedars-Sinai医疗癌症中心的放射肿瘤学教授Howard Sandler说，“该研究首次阐明化疗在局部前列腺癌的辅助治疗中的作用。随着时间的推移，我们也希望看到更大的生存优势。这一发现可能会改善成千上万患者的治疗效果。同时，化疗也带来了一定的副作用，所以医生与患者讨论获益和风险的平衡是很重要的。”
辅助治疗是在患者完成其肿瘤主要治疗（如手术或放疗）后的附加治疗。辅助治疗的目的是降低复发风险和改善总生存。在最常见的肿瘤——肺癌、乳腺癌、结直肠癌和前列腺癌中——前列腺癌是唯一没有建立辅助化疗方案的疾病。
在这项研究中，562例高危、局部晚期前列腺癌患者被随机分配到标准治疗组（放疗加两年的内分泌治疗）或标准治疗后加多西他赛化疗组。多西他赛共给予18周，放疗后1个月开始给药。
平均随访5.5年后，标准治疗组和多西他赛化疗组死亡患者例数分别为52例和36例；四年总存活率分别为89%和93%。多西他赛还可以降低复发风险—标准治疗组和多西他赛化疗组的五年无病生存率分别为66%和73%。
该研究将会继续随访患者以确定辅助化疗在这种情况下的长期益处，稍后将会公布患者生存质量分析数据。Sandler 指出未来的研究将会探讨辅助治疗对高危、局部前列腺癌患者的影响。
摘要原文
Background: High-risk, localized prostate cancer (PCa) patients have a relatively poor prognosis. We hypothesized that the addition of adjuvant docetaxel and prednisone to long-term (24 month) AS and radiation therapy (RT) would improve overall survival (OS).
Methods: RTOG 0521 opened December 2005 and closed August 2009 with targeted accrual of 600 cases. It was designed to detect improvement in 4-year OS from 86% to 93% with a 51% hazard reduction (HR = 0.49). Under a 0.05 1-sided type I error and 90% power, at least 78 deaths were required to analyze the OS endpoint. Patients had 1) Gleason (Gl) 7-8, any T-stage, and PSA > 20, or 2) Gl 8, ≥ T2, any PSA, or 3) Gl 9-10, any T-stage, any PSA. All had PSA ≤ 150. RT dose was 75.6 Gy. CT consisted of 6, 21-day cycles of docetaxel + prednisone starting 28 days after RT.
Results: Of 612 enrolled, 50 were excluded for eligibility issues, leaving 562 evaluable. Median age = 66, median PSA = 15.1, 53% had Gl 9-10, 27% had cT3-4. Median follow-up = 5.5 yrs. 4-yr OS rates were 89% [95% CI: 84-92%] for the AS+RT arm and 93% [95% CI: 90-96%] for the AS+RT+CT arm (1-sided p = 0.03, HR = 0.68 [95% CI: 0.44, 1.03]). There were 52 centrally-reviewed deaths in the AS+RT arm and 36 in the AS+RT+CT arm, with fewer deaths both due to PCa/treatment (20 vs 16) and due to other causes/unknown (32 vs 20) in the AS+RT+CT arm. 5-yr disease-free survival rates were 66% for AS+RT and 73% for AS+RT+CT (2-sided p = 0.05, HR = 0.76 [95% CI: 0.57, 1.00]). There was 1, Gr 5 unlikely-related adverse event (AE) in the AS+RT arm and 2, Gr 5 possibly/probably-related AEs with AS+RT+CT.
Conclusions: For high-risk, localized PCa,adjuvant CT improved the OS from 89% to 93% at 4 years. Toxicity was acceptable. This trial was designed with a short OS assessment period and additional follow-up is warranted to determine the long-term benefit of CT to the current standard of care of long-term AS+RT. This project was supported by grants U10CA21661, U10CA180868, U10CA180822, from the National Cancer Institute and Sanofi with additional support from AstraZeneca for Australian site participation.
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