BACKGROUND Up to 50% of men with poor prognosis, non-seminoma germ cell tumours (GCTs) die with standard BEP (bleomycin, etoposide and cisplatin) chemotherapy. An intensive regimen, CBOP/BEP (carboplatin, bleomycin, vincristine and cisplatin/BEP), met response targets in a randomised, phase II trial (74% complete response or partial response marker negative, 90% confidence interval (CI) 61%-85%). AIM To assess long-term outcomes and late toxicity associated with CBOP/BEP. METHODS Patients with poor prognosis extracranial GCT were randomised to 4xBEP or CBOP/BEP (2xCBOP, 2xBO, 3xBEP with 15,000iu of bleomycin). Low-dose, stabilising chemotherapy before entry was permitted. Response rates (primary outcome) were reported previously. Here, we report secondary outcomes: progression-free survival (PFS), overall survival (OS) and late toxicity. Prognostic factors and the impact of marker decline are assessed in exploratory analysis. RESULTS Eighty-nine patients (43 CBOP/BEP) were randomised. After median 63 months follow-up, 3-year PFS is 55.7% (95% CI: 39.7%, 69.0%) for CBOP/BEP and 38.7% (95% CI: 24.7%, 52.4%) for BEP (hazard ratio [HR]: 0.59 (0.33, 1.06), p = 0.079). Three-year OS is 65.0% (48.8%, 77.2%) and 58.5% (43.0%, 71.2%), respectively (HR: 0.79 (0.41, 1.52), p = 0.49). Twelve-month toxicity was affected by subsequent treatments, with no clear differences between arms. Stabilising chemotherapy was associated with poorer PFS (HR: 2.09 (1.14, 3.81), p = 0.017), whereas unfavourable marker decline, in 60 (70%) patients, was not. CONCLUSION Although not powered for PFS, results for CBOP/BEP are promising. Impact on OS was less clear (and will be affected by subsequent therapy). Further study in an international phase III trial is warranted. TRIAL REGISTRATION ISRCTN 53643604.

中文翻译：

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强化诱导化疗（卡铂，博来霉素，长春新碱和顺铂/博来霉素，依托泊苷和顺铂）和标准博来霉素，依托泊苷和顺铂在预后不良的生殖细胞肿瘤中的长期疗效：一项II期随机试验（ISRCTN53643604）。

背景技术高达50％的预后不良的男性因标准BEP（博来霉素，依托泊苷和顺铂）化疗而死亡，非精原细胞生殖细胞肿瘤（GCT）。一项密集的方案CBOP / BEP（卡铂，博来霉素，长春新碱和顺铂/ BEP）在一项随机的II期临床试验中达到了缓解目标（74％完全缓解或部分缓解指标阴性，90％置信区间（CI）61％- 85％）。目的评估与CBOP / BEP相关的长期结果和晚期毒性。方法将预后不良的颅外GCT患者随机分为4xBEP或CBOP / BEP（2xCBOP，2xBO，3xBEP和博来霉素15,000iu）。允许在进入前进行小剂量，稳定化疗。反应率（主要结局）先前已有报道。在这里，我们报告了次要结果：无进展生存期（PFS），总体生存期（OS）和晚期毒性。在探索性分析中评估预后因素和标志物下降的影响。结果八十九例患者（43 CBOP / BEP）被随机分组​​。中位63个月的随访后，CBOP / BEP的3年PFS为55.7％（95％CI：39.7％，69.0％），而BEP的38.7％（95％CI：24.7％，52.4％）（危险比[ [HR]：0.59（0.33，1.06），p ＝ 0.079）。三年OS分别为65.0％（48.8％，77.2％）和58.5％（43.0％，71.2％）（HR：0.79（0.41，1.52），p = 0.49）。十二个月的毒性受到后续治疗的影响，两组之间无明显差异。稳定的化疗与较差的PFS相关（HR：2.09（1.14，3.81），p = 0.017），而60例（70％）患者的不良标志物下降并非如此。结论尽管没有为PFS提供支持，但CBOP / BEP的结果很有希望。对OS的影响尚不清楚（并将受到后续治疗的影响）。有必要在国际III期试验中进行进一步研究。试用注册号ISRCTN 53643604。