Phase 2 Study of Cyclophosphamide, Etoposide, and Estramustine in Patients With Castration-Resistant Prostate Cancer
Phase 2 Study of Cyclophosphamide, Etoposide, and Estramustine in Patients With Castration-Resistant Prostate Cancer
复制标题
环磷酰胺、依托泊苷和雌莫司汀治疗去势抵抗性前列腺癌患者的 2 期研究。
DOI：
10.1016/j.clgc.2018.06.007
复制
发表时间：
2018-12-01
影响因子：
3.2
通讯作者：
Visweshwar, Nathan
中科院分区：
文献类型：
--
作者：
Laber, Damian A.;Chen, Min-Bin;Visweshwar, Nathan
对于转移性去势抵抗性前列腺癌（mCRPC）患者，没有有效的化疗方法，这些患者的疾病必须对紫杉烷治疗有反应或不希望接受静脉内药物。口服环磷酰胺、依托泊苷和雌莫司汀（CEE）治疗mCRPC.Background的2期研究发现，CEE是一种耐受性良好、易于管理且有效的治疗mCRPC.Background患者的方法：对于转移性去势抵抗性前列腺癌（mCRPC）患者，紫杉烷类药物治疗无效或不希望接受静脉药物治疗的患者，尚无有效的化疗方法。我们假设，低剂量的多种药物与长期暴露将导致高反应率和低毒性。患者和方法：mCRPC患者有资格参加这项II期试验。主要终点是前列腺特异性抗原降低超过50%。CEE包括环磷酰胺（50 mg/m2）、依托泊苷（50 mg/m2）和雌莫司汀（280 mg），口服，每日1次，每28天14天为1周期。结果：52例患者入组并纳入所有评价。所有患者的前列腺特异性抗原应答率为46%，化疗初治患者为53%，多西他赛化疗后为31%。30例受试者有可测量的病变，1例（3%）完全缓解，2例（7%）部分缓解，22例（73%）疾病稳定，临床获益为83%。60%的人在他们的表现状态方面有所改善，65%的人报告他们的疼痛有所改善。所有患者的中位总生存期为18.6个月，化疗初治患者为20.4个月，多西他赛治疗期间疾病进展的患者为11.3个月。3/4级治疗相关毒性包括20%中性粒细胞减少、10%血小板减少、10%深静脉血栓形成、8%贫血、8%疲乏、4%死亡和2%厌食和口腔炎。结论：CEE是治疗mCRPC患者的一种全口服、易于给药且有效的三联药物治疗。(C)2018爱思唯尔公司All rights reserved.
There are no effective chemotherapies for patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease has have to respond to taxane therapy or who do not wish to receive intravenous drugs. A phase 2 study of oral cyclophosphamide, etoposide, and estramustine (CEE) in mCRPC found that CEE was a well-tolerated, easy-to-administer, and effective therapy for patients with mCRPC.Background: There are no effective chemotherapies for patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease has failed to respond to taxanes or patients who do not wish to receive intravenous drugs. We hypothesized that low doses of multiple medications with prolonged exposure would result in a high response rate and low toxicity. Patients and Methods: Patients with mCRPC were eligible for this phase 2 trial. The primary endpoint was a prostate-specific antigen decrease of more than 50%. CEE consisted of cyclophosphamide (50 mg/m(2)), etoposide (50 mg/m(2)), and estramustine 280 mg provided orally once a day for 14-day cycles every 28 days. Results: Fifty-two patients were enrolled and included in all evaluations. The prostate-specific antigen response rate was 46% in all patients, 53% in chemotherapy-naive subjects, and 31% after docetaxel chemotherapy. Thirty subjects had measurable lesions, 1 (3%) had complete response, 2 (7%) partial response, and 22 (73%) stable disease, for a clinical benefit of 83%. Sixty percent experienced an improvement in their performance status, and 65% reported improvement in their pain. The median overall survival was 18.6 months in all patients, 20.4 months in chemotherapy-naive patients and 11.3 months in patients whose disease progressed while receiving docetaxel therapy. Grade 3/4 treatment-related toxicities included 20% neutropenia, 10% thrombocytopenia, 10% deep-vein thrombosis, 8% anemia, 8% fatigue, 4% death, and 2% anorexia and stomatitis. Conclusion: CEE was an all-oral, easy-to-administer, and effective triple-drug therapy for patients with mCRPC. (C) 2018 Elsevier Inc. All rights reserved.