Phase III Trial of Androgen Ablation With or Without Three Cycles of Systemic Chemotherapy for Advanced Prostate Cancer
Phase III Trial of Androgen Ablation With or Without Three Cycles of Systemic Chemotherapy for Advanced Prostate Cancer
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DOI：
10.1200/jco.2007.15.9830
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发表时间：
2008-12-20
影响因子：
45.3
通讯作者：
Logothetis, Christopher J.
中科院分区：
文献类型：
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作者：
Millikan, Randall E.;Wen, Sijin;Logothetis, Christopher J.
目的：我们在既往未经治疗的转移性前列腺癌患者中进行了一项III期临床试验，以检验以下假设：在标准雄激素剥夺的基础上，会延迟阉割的出现患者和方法符合条件的患者患有足以证明持续雄激素消融的转移性前列腺癌，足够化疗了主要终点是去势抵抗进展的时间，如增加前列腺特异性抗原，新的放射学病变，恶化的癌症相关症状，或接受任何其他全身性therapy.ResultsThree百6例患者登记，286报告。标准治疗组的中位进展时间为24个月（95%CI，18至39个月），化学激素组为35个月（95%CI，26至44个月）（P = 0.39）。中位随访时间为6.4年，标准治疗组的总生存期为5.4年（95% CI，4.7 - 7.8年），而对照组为6.1年（95% CI，5.1 - 10.1年; P = 0.41）。雄激素去除时和激素治疗后最低点的前列腺特异性抗原动力学与生存率密切相关。化疗显着增加了治疗的负担，51%的患者经历了3级或更糟的不良事件，特别是血栓栓塞events.ConclusionThere是没有作用的酮康唑和阿霉素交替长春碱和雌莫司汀出现前的去势抵抗表型。
PurposeWe conducted a phase III trial in patients with previously untreated metastatic prostate cancer to test the hypothesis that three 8-week cycles of ketoconazole and doxorubicin alternating with vinblastine and estramustine, given in addition to standard androgen deprivation, would delay the appearance of castrate-resistant disease.Patients and MethodsEligible patients had metastatic prostate cancer threatening enough to justify sustained androgen ablation and were fit enough for chemotherapy. The primary end point was time to castrate-resistant progression as shown by increasing prostate-specific antigen, new radiographic lesions, worsening cancer-related symptoms, or receipt of any other systemic therapy.ResultsThree hundred six patients were registered; 286 are reported. Median time to progression was 24 months ( 95% CI, 18 to 39 months) in the standard therapy arm, and 35 months ( 95% CI, 26 to 44 months) in the chemohormonal group ( P = .39). At median follow-up of 6.4 years, overall survival was 5.4 years ( 95% CI, 4.7 to 7.8 years) in the standard therapy arm versus 6.1 years ( 95% CI, 5.1 to 10.1 years; P = .41). Prostate-specific antigen kinetics at the time of androgen ablation and the nadir after hormone treatment were strongly correlated with survival. Chemotherapy significantly increased the burden of therapy, with 51% of patients experiencing an adverse event of grade 3 or worse, especially thromboembolic events.ConclusionThere is no role for ketoconazole and doxorubicin alternating with vinblastine and estramustine before emergence of a castrate-resistant phenotype.