Ishioka S
2nd Dept. of Internal Medicine, Hiroshima University School of Medicine.
Gan To Kagaku Ryoho. 1997 Oct;24 Suppl 3:432-8.
Pulmonary disease induced by chemotherapeutic drug or radiation is one of the major cause, of death in patients with lung cancer. Many of these patients die from interstitial lung disease despite discontinuation of the drug and addition of corticosteroid treatment. The clinical presentation is similar for all of the chemotherapeutic drugs. For the early detection of interstitial lung disease due to a chemotherapeutic drug, serial measurements of the CO diffusing capacity (DLco), serum LDH, and serum KL-6 are useful. The first step in treatment is withdrawal of the drugs, and pulse therapy by using methylprednisolone is used as a standard therapy for interstitial lung disease due to chemotherapeutic agents. Immunosuppressive agents, such as cyclophosphamide or azathioprine, might be used as second-line drugs in patients for whom drugs either failed or could not tolerate corticosteroid treatment. Thus the usefulness of this therapy is unknown, and it should be considered as a marginal therapy. To develop an investigational therapy for the chemotherapeutic drug-induced interstitial lung disease, we investigated the efficacy of a new specific neutrophil elastase inhibitor (ONO-5046.Na) in bleomycin-induced pulmonary fibrosis. The inhibitory effect of ONO-5046.Na was observed in bleomycin-induced pulmonary fibrosis in mice. This specific neutrophil elastase could be a investigational therapeutic agent for interstitial lung disease due to chemotherapeutic agents used against lung cancer.
化疗药物或放疗所致肺部疾病是肺癌患者主要死因之一。尽管停用了药物并加用了皮质类固醇治疗，许多此类患者仍死于间质性肺病。所有化疗药物的临床表现相似。为早期发现化疗药物所致间质性肺病，连续测量一氧化碳弥散量（DLco）、血清乳酸脱氢酶（LDH）和血清KL-6很有用。治疗的第一步是停用药物，使用甲泼尼龙进行冲击治疗是化疗药物所致间质性肺病的标准治疗方法。免疫抑制剂，如环磷酰胺或硫唑嘌呤，可作为药物治疗失败或不能耐受皮质类固醇治疗患者的二线药物。然而这种治疗方法的有效性尚不清楚，应视为边缘性治疗。为开发针对化疗药物所致间质性肺病的研究性治疗方法，我们研究了一种新型特异性中性粒细胞弹性蛋白酶抑制剂（ONO-5046.Na）对博来霉素诱导的肺纤维化的疗效。在博来霉素诱导的小鼠肺纤维化中观察到了ONO-5046.Na的抑制作用。这种特异性中性粒细胞弹性蛋白酶可能是针对肺癌化疗药物所致间质性肺病的一种研究性治疗药物。
