O'Sullivan J M, Huddart R A, Norman A R, Nicholls J, Dearnaley D P, Horwich A
Academic Unit of Radiotherapy and Clinical Oncology, The Institute of Cancer Research, Royal Marsden NHS Trust, Sutton, UK.
Ann Oncol. 2003 Jan;14(1):91-6. doi: 10.1093/annonc/mdg020.
Bleomycin pulmonary toxicity (BPT) has been known since the early clinical trials of bleomycin in the 1960s. Postulated risk factors include cumulative bleomycin dose, reduced glomerular filtration rate (GFR), raised creatinine, older age and supplemental oxygen exposure.
From our prospectively collected testicular cancer research database, we reviewed 835 patients treated at the Royal Marsden NHS Trust (Sutton, UK) with bleomycin-containing regimens for germ-cell tumours between January 1982 and December 1999, to identify those with BPT.
Fifty-seven (6.8%) patients had BPT, ranging from X-ray/CT (computed tomography) changes to dyspnoea. There were eight deaths (1% of patients treated) directly attributed to BPT. The median time from the start of bleomycin administration to documented lung toxicity was 4.2 months (range 1.2-8.2). On multivariate analysis, the factors independently predicting for increased risk of BPT were GFR <80 ml/min [hazard ratio (HR) 3.3], age >40 years (HR 2.3), stage IV disease at presentation (HR 2.6) and cumulative dose of bleomycin >300,000 IU (HR 3.5).
Patients with poor renal function are at high risk of BPT, especially if they are aged >40 years, have stage IV disease at presentation or receive >300,000 IU of bleomycin. In such cases alternative drug regimens or dose restriction should be considered.
自20世纪60年代博来霉素进行早期临床试验以来，人们就已了解到博来霉素所致肺毒性（BPT）。推测的风险因素包括博来霉素累积剂量、肾小球滤过率（GFR）降低、肌酐升高、年龄较大以及暴露于补充氧气环境。
从我们前瞻性收集的睾丸癌研究数据库中，我们回顾了1982年1月至1999年12月期间在英国皇家马斯登国民保健服务信托基金（萨顿）接受含博来霉素方案治疗生殖细胞肿瘤的835例患者，以确定那些发生BPT的患者。
57例（6.8%）患者发生BPT，表现从X线/CT（计算机断层扫描）改变到呼吸困难。有8例死亡（占接受治疗患者的1%）直接归因于BPT。从开始使用博来霉素至记录到肺部毒性的中位时间为4.2个月（范围1.2 - 8.2个月）。多因素分析显示，独立预测BPT风险增加的因素为GFR<80 ml/分钟[风险比（HR）3.3]、年龄>40岁（HR 2.3）、就诊时为IV期疾病（HR 2.6）以及博来霉素累积剂量>300,000 IU（HR 3.5）。
肾功能不佳的患者发生BPT的风险很高，尤其是如果他们年龄>40岁、就诊时为IV期疾病或接受>300,000 IU的博来霉素。在这种情况下，应考虑替代药物方案或剂量限制。
