Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial
Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial
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DOI：
10.1016/s1470-2045(12)70560-0
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发表时间：
2013-02-01
期刊：
影响因子：
51.1
通讯作者：
Soulie, Michel
中科院分区：
文献类型：
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作者：
Gravis, Gwenaelle;Fizazi, Karim;Soulie, Michel
背景早期化疗可能改善转移性非去势(即激素敏感型)前列腺癌患者的整体预后。我们研究了在雄激素剥夺疗法(ADT)的基础上加用多西他赛对转移性非去势前列腺癌患者的影响。方法在这项随机开放的3期研究中，我们在法国的29个中心和比利时的一个中心招募了患者。符合条件的患者年龄超过18岁，有组织学证实的前列腺癌和放射学证实的转移性疾病；Karnofsky评分至少70%；预期寿命至少3个月；以及足够的肝、血液和肾功能。他们被随机分配接受ADT(切除或黄体化激素释放激素激动剂，单独或与非类固醇抗雄激素联合使用)或与多西紫杉醇(每21天周期的第一天静脉注射75 mg/m(2)；最多9个周期)。患者按1：1的比例随机进行，动态最小化以最大限度地减少以前使用ADT、局部疾病化疗或单独的血清前列腺特异性抗原浓度升高的全身治疗中的失衡，以及Glass Risk组。患者、医生和数据分析师没有被掩饰到治疗分配中。主要终点是总体存活率。按意向处理进行疗效分析。这项试验已在临床试验中注册。GOV，编号NCT00104715。2004年10月18日至2008年12月31日，192名患者被随机分配接受ADT加多西紫杉醇治疗，193名患者仅接受ADT治疗。中位随访期为50个月(IQR 39~63)。ADT联合多西紫杉醇治疗组的中位总生存期为58.9个月(95%CI为50.8~69.1)，单用ADT组的中位总生存期为54.2个月(42.2个月未达)(风险比1.01，95%CI为0.75~1.36)。ADT加多西紫杉醇治疗组共发生72例严重不良反应，其中最常见的是中性粒细胞减少症40例(21%)，发热中性粒细胞减少症6例(3%)，肝功能异常3例(2%)，中性粒细胞减少合并感染2例(1%)。ADT加多西紫杉醇治疗组发生4例与治疗相关的死亡(其中两例与中性粒细胞减少症有关)，之后数据监测委员会建议使用粒细胞集落刺激因子治疗。在这一建议之后，没有发生与治疗相关的进一步死亡。单用ADT组未报告严重不良事件。多西他赛不应作为非去势转移性前列腺癌患者一线治疗的一部分。
Background Early chemotherapy might improve the overall outcomes of patients with metastatic non-castrate (ie, hormone-sensitive) prostate cancer. We investigated the effects of the addition of docetaxel to androgen-deprivation therapy (ADT) for patients with metastatic non-castrate prostate cancer.Methods In this randomised, open-label, phase 3 study, we enrolled patients in 29 centres in France and one in Belgium. Eligible patients were older than 18 years and had histologically confirmed adenocarcinoma of the prostate and radiologically proven metastatic disease; a Karnofsky score of at least 70%; a life expectancy of at least 3 months; and adequate hepatic, haematological, and renal function. They were randomly assigned to receive to ADT (orchiectomy or luteinising hormone-releasing hormone agonists, alone or combined with non-steroidal antiandrogens) alone or in combination with docetaxel (75 mg/m(2) intravenously on the first day of each 21-day cycle; up to nine cycles). Patients were randomised in a 1:1 ratio, with dynamic minimisation to minimise imbalances in previous systemic treatment with ADT, chemotherapy for local disease or isolated rising concentration of serum prostate-specific antigen, and Glass risk groups. Patients, physicians, and data analysts were not masked to treatment allocation. The primary endpoint was overall survival. Efficacy analyses were done by intention to treat. This trial is registered with ClinicalTrials. gov, number NCT00104715.Findings Between Oct 18, 2004, and Dec 31, 2008, 192 patients were randomly allocated to receive ADT plus docetaxel and 193 to receive ADT alone. Median follow-up was 50 months (IQR 39-63). Median overall survival was 58.9 months (95% CI 50.8-69.1) in the group given ADT plus docetaxel and 54.2 months (42.2-not reached) in that given ADT alone (hazard ratio 1.01, 95% CI 0.75-1.36). 72 serious adverse events were reported in the group given ADT plus docetaxel, of which the most frequent were neutropenia (40 [21%]), febrile neutropenia (six [3%]), abnormal liver function tests (three [2%]), and neutropenia with infection (two [1%]). Four treatment-related deaths occurred in the ADT plus docetaxel group (two of which were neutropenia-related), after which the data monitoring committee recommended treatment with granulocyte colony-stimulating factor. After this recommendation, no further treatment-related deaths occurred. No serious adverse events were reported in the ADT alone group.Interpretation Docetaxel should not be used as part of first-line treatment for patients with non-castrate metastatic prostate cancer.