Division of Oncology, Department of Internal Medicine, University of Texas Health Science Center at Houston (Medical School)/Memorial Hermann Cancer Center, 6410 Fannin St., Suite 830, Houston, TX 77030, USA.
Cancer Chemother Pharmacol. 2013 Jun;71(6):1629-34. doi: 10.1007/s00280-013-2163-4. Epub 2013 Apr 21.
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.
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疗的患者初始治疗的安全性和有效性。
入组患者接受每 12 周一次的亮丙瑞林 ADT，共 24 个月，在化疗完成后开始使用比卡鲁胺。化疗方案为酮康唑和阿霉素，第 1、3 和 5 周；依托泊苷和多西他赛，第 2、4 和 6 周；第 7 和 8 周不接受治疗。
共入组 46 例患者，45 例患者可评估。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 例可测量疾病患者中，22 例有客观缓解：9 例完全缓解；2 例部分缓解；10 例疾病稳定。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%）。罕见的 4 级不良事件包括低碳酸氢盐（2%）、低钾血症（2%）、白细胞减少（2%）和中性粒细胞减少（2%）。
该治疗方案在所有患者亚组中均显示出临床获益，且治疗相关的不良反应可逆转。亚组分析表明，先前的局部治疗可带来更长的 PFS 和 OS。
