Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7295, USA.
BJU Int. 2012 Dec;110(11 Pt B):E721-6. doi: 10.1111/j.1464-410X.2012.11536.x. Epub 2012 Sep 27.
Study Type - Therapy (phase 1) Level of Evidence 2a What's known on the subject? and What does the study add? High-risk and locally advanced prostate cancers are difficult to cure with the standard regimen of radiation therapy (RT) with concurrent androgen-deprivation therapy (ADT). Multiple studies have explored the addition of docetaxel chemotherapy in attempt to improve patient outcomes. Prior Phase I studies have shown that docetaxel 20 mg/m(2) is a safe dose, when given concurrently with 70 Gy of radiation. But current standard RT for prostate cancer uses higher doses, and it is unclear if concurrent chemotherapy is safe with modern RT. This is a Phase I study that explored the addition of concurrent docetaxel chemotherapy to modern RT (intensity-modulated RT to 78 Gy) plus ADT. The study showed that weekly docetaxel at 20 mg/m(2) is safe with modern RT. At a median follow-up of 2.2 years, biochemical progression-free survival was 94%. This triple-therapy regimen is safe and promising for further evaluation in prospective trials.
• To evaluate in a phase I trial, the feasibility of adding concurrent weekly docetaxel chemotherapy to high-dose intensity modulated radiation therapy (IMRT) and androgen-deprivation therapy (ADT) for treatment of high-risk prostate cancer.
• Patients with high-risk prostate cancer were treated with a luteinising hormone-releasing hormone agonist (starting 2-3 months before IMRT and lasting 2 years), IMRT of 78 Gy to the prostate and seminal vesicles, and weekly docetaxel during RT. • All patients had computed tomography and bone scans to exclude metastatic disease. • A standard 3 + 3 design was used for docetaxel dose escalation. Successive patients were treated on dose levels of 10, 15, and 20 mg/m(2) of weekly docetaxel.
• In all, 18 patients participated in the study: 15 (83%) had Gleason 8-10 disease; the other three had either clinical T3 disease and/or a prostate-specific antigen (PSA) level of >20 ng/mL. • Grade 3 diarrhoea (a defined dose-limiting toxicity, DLT) occurred in one patient in each of the first two dose levels. However, when the cohorts were expanded, no further DLT was seen. • Weekly docetaxel at 20 mg/m(2) (dose level 3) was successfully given without DLT. • No patient had grade 4 or 5 toxicity. • At a median follow-up of 2.2 years, all patients achieved a PSA nadir of <1 ng/mL, including 13 patients who had an undetectable PSA level. The 2-year biochemical progression-free survival was 94%.
• A dose of 20 mg/m(2) of weekly docetaxel given concurrently with high-dose IMRT and ADT appears safe for further study in patients with high-risk prostate cancer.
研究类型-治疗（1 期）证据水平 2a 关于该主题已知的内容是什么？以及这项研究有什么新发现？高危和局部晚期前列腺癌用标准的放射治疗（RT）联合雄激素剥夺疗法（ADT）很难治愈。多项研究探索了添加多西他赛化疗以尝试改善患者预后。先前的 1 期研究表明，当与 70Gy 放射治疗联合使用时，多西他赛 20mg/m²是安全剂量。但目前前列腺癌的标准 RT 使用更高的剂量，目前尚不清楚现代 RT 联合化疗是否安全。这是一项探索在现代 RT（强度调节 RT 至 78Gy）联合 ADT 的基础上添加同步多西他赛化疗的 1 期研究。研究表明，每周 20mg/m²的多西他赛与现代 RT 联合使用是安全的。中位随访 2.2 年后，生化无进展生存率为 94%。这种三联疗法对于进一步在前瞻性试验中评估是安全且有希望的。
在 1 期试验中评估，将每周多西他赛联合高剂量调强放射治疗（IMRT）和雄激素剥夺治疗（ADT）用于治疗高危前列腺癌的可行性。
高危前列腺癌患者接受促黄体激素释放激素激动剂（在开始 IMRT 前 2-3 个月开始，持续 2 年）、前列腺和精囊的 78Gy IMRT 以及放射治疗期间每周多西他赛治疗。所有患者均接受计算机断层扫描和骨扫描以排除转移性疾病。使用标准的 3+3 设计进行多西他赛剂量递增。连续患者接受每周多西他赛 10、15 和 20mg/m²的剂量水平治疗。
共有 18 名患者参与了这项研究：15 名（83%）患者患有 Gleason 8-10 疾病；另外 3 名患者有临床 T3 疾病和/或 PSA 水平>20ng/mL。在头两个剂量水平中，各有一名患者出现 3 级腹泻（定义为剂量限制性毒性，DLT）。然而，当扩大队列时，没有观察到其他 DLT。每周 20mg/m²（剂量水平 3）的多西他赛成功给予，没有 DLT。没有患者发生 4 级或 5 级毒性。中位随访 2.2 年后，所有患者的 PSA 均达到<1ng/mL 的最低点，包括 13 名 PSA 水平不可检测的患者。2 年的生化无进展生存率为 94%。
高危前列腺癌患者每周 20mg/m²的多西他赛与高剂量 IMRT 和 ADT 联合应用的剂量似乎是安全的，可进一步研究。
