A phase II trial of androgen deprivation therapy (ADT) plus chemotherapy as initial treatment for local failures or advanced prostate cancer
A phase II trial of androgen deprivation therapy (ADT) plus chemotherapy as initial treatment for local failures or advanced prostate cancer
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DOI：
10.1007/s00280-013-2163-4
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发表时间：
2013-06-01
影响因子：
3
通讯作者：
Gonzales, Patricia
中科院分区：
文献类型：
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作者：
Amato, Robert;Stepankiw, Mika;Gonzales, Patricia
前列腺癌的长期激素消融与整体健康和生活质量下降有关。很少有报道强调化疗在早期前列腺癌治疗中的作用。本研究分析了雄激素剥夺治疗（ADT）加化疗作为局部失败或因晚期疾病表现而不适合前列腺切除术或放射治疗的患者的初始治疗的安全性和有效性。入组的患者每12周一次接受亮丙瑞林形式的ADT，持续24个月，化疗完成后开始比卡鲁胺治疗。化疗包括第1、3和5周的酮康唑和多柔比星以及第2、4和6周的雌莫司汀和多西他赛。在第7周和第8周期间，没有接受任何治疗。46名患者入组，45名患者可评价。中位无进展生存期（PFS）为23.4个月。中位总生存期（OS）为53.7个月。在45例可测量疾病的患者中，22例患者达到客观缓解：9例患者达到完全缓解; 2例患者达到部分缓解; 10例患者达到疾病稳定。常见的3级不良事件包括ALT升高（17%）、低钾血症（13%）和低磷血症（13%）。4级不良事件罕见，包括低碳酸氢盐（2%）、低钾血症（2%）、白细胞减少（2%）和中性粒细胞减少（2%）。亚组分析表明，既往接受过局部治疗的患者PFS和OS更高。
Long-term hormonal ablation in prostate cancer is associated with decreased overall health and quality of life. Few reports emphasized the role of chemotherapy in the management of early stage prostate cancer. This study analyzed the safety and efficacy of androgen deprivation therapy (ADT) plus chemotherapy as initial treatment for patients identified as local failures or not eligible for prostatectomy or radiation therapy due to advanced disease presentation.Enrolled patients received ADT in the form of leuprolide every 12 weeks for 24 months with bicalutamide initiating after the completion of chemotherapy. Chemotherapy consisted of ketoconazole and doxorubicin for weeks 1, 3, and 5 and estramustine and docetaxel and for weeks 2, 4 and 6. During weeks 7 and 8, no treatment was received.Forty-six patients were enrolled, and forty-five patients were evaluable. Median progression-free survival (PFS) was 23.4 months. Median overall survival (OS) was 53.7 months. Out of 45 patients with measurable disease, 22 patients had an objective response: 9 patients achieved a complete response; 2 patients achieved a partial response; 10 patients achieved stable disease. Frequent grade 3 adverse events included elevated ALT (17 %), hypokalemia (13 %), and hypophosphatemia (13 %). Grade 4 adverse events were rare and included low bicarbonate (2 %), hypokalemia (2 %), leukocytopenia (2 %), and neutropenia (2 %).The treatment demonstrated clinical benefit in all patient subsets with minimal reversible treatment-related adverse events. Subgroup analysis suggests that having prior local therapy resulted in greater PFS and OS.