Centre for Experimental Cancer Medicine, Barts Cancer Institute, QMUL, London.
Academic Unit of Radiotherapy & Oncology, Institute of Cancer Research, London.
Ann Oncol. 2017 Jun 1;28(6):1333-1338. doi: 10.1093/annonc/mdx071.
Bleomycin is an integral part of combination chemotherapy in germ cell tumours. Pulmonary toxicity often necessitates drug cessation and death occurs in 1%-2% of patients. A continuous infusion of bleomycin might reduce lung toxicity when compared with the conventional weekly boluses given as part of standard BEP chemotherapy.
A phase 3 trial was conducted based on 212 men with IGCCCG good prognosis metastatic germ cell tumours with 1 : 1 randomization. They were stratified for age, smoking history and renal function. Patients received either conventional BEP with weekly bleomycin (30 000 units/week i.v. bolus) or as a 90 000 unit infusion on day 1 over 72 h. The primary endpoint was CT assessed lung toxicity, secondary endpoints included progression-free survival (PFS), changes in lung function testing and quality of life. Repeated measures mixed effects model was used to analyse the data.
CT assessed lung toxicity for the infusional and conventional arm patients were respectively 80% versus 62% at the end of treatment and 54% versus 51% at 1-year post-treatment. There was no significant difference between the two arms for CT assessed lung toxicity (estimated regression coefficient = 1.4, 95% CI: -0.36, 3.16). Older patients had higher toxicity (coefficient = 4.81, 95% CI: 3.04, 6.58). Lung toxicity increased after 1 cycle and peaked at end of treatment (P ≤ 0.002) and then declined. Lung function testing did not predict for subsequent lung damage. The median follow-up was 2.5 years. Two-year PFS rate (infusional: 93%, conventional: 94%; hazard ratio =0.91, 95% CI: 0.33, 2.52) was similar. Cough (P = 0.002) but not shortness of breath (P ≥ 0.09) was associated with bleomycin toxicity.
Infusional bleomycin has no advantage over standard administration. It supports abandoning routine pulmonary function testing, instead the presence of cough should be sought and the early use of CT scanning of the chest to evaluate potential lung toxicity is preferred.
博来霉素是生殖细胞肿瘤联合化疗的重要组成部分。肺毒性常导致药物停止使用，1%-2%的患者死亡。与标准 BEP 化疗中每周给予博来霉素的常规推注相比，连续输注博来霉素可能会降低肺毒性。
基于 212 名 IGCCCG 预后良好的转移性生殖细胞肿瘤男性患者进行了一项 3 期试验，采用 1:1 随机分组。他们根据年龄、吸烟史和肾功能进行分层。患者接受常规 BEP 治疗，每周给予博来霉素（30000 单位/周静脉推注）或第 1 天给予 90000 单位博来霉素输注，持续 72 小时。主要终点为 CT 评估的肺毒性，次要终点包括无进展生存期（PFS）、肺功能测试变化和生活质量。采用重复测量混合效应模型分析数据。
治疗结束时，输注组和常规组的 CT 评估肺毒性分别为 80%和 62%，治疗后 1 年分别为 54%和 51%。两组之间 CT 评估的肺毒性无显著差异（估计回归系数为 1.4，95%CI：-0.36，3.16）。年龄较大的患者毒性更高（系数为 4.81，95%CI：3.04，6.58）。肺毒性在 1 个周期后增加，并在治疗结束时达到高峰（P≤0.002），然后下降。肺功能测试不能预测随后的肺损伤。中位随访时间为 2.5 年。输注组和常规组的 2 年 PFS 率（分别为 93%和 94%；危险比为 0.91，95%CI：0.33，2.52）相似。咳嗽（P=0.002）而非呼吸困难（P≥0.09）与博来霉素毒性相关。
输注博来霉素与标准给药相比没有优势。它支持放弃常规肺功能测试，而应寻求咳嗽的存在，并优先使用胸部 CT 扫描评估潜在的肺毒性。
