Zimmerman M S, Ruckdeschel J C, Hussain M
J Clin Oncol. 1984 May;2(5):396-405. doi: 10.1200/JCO.1984.2.5.396.
Twelve cases of interstitial pneumonitis were seen in 50 patients (24%) treated with cyclophosphamide, methotrexate, and etoposide (VP-16-213) for small cell anaplastic lung cancer. The clinical course and pathologic characteristics were consistent with drug-induced pneumonitis in all 12 cases. One additional patient had concurrent histologic evidence of interstitial pneumonitis, pneumocystis infection, and perivascular metastases. Patients presented with severe dyspnea, hypoxemia, cough, fever, and bilateral interstitial infiltrates on chest films. The onset was rapid and unpredictable, following as little as one month or as much as five months of therapy. Nine patients recovered but there were three deaths in the acute period directly attributable to the drug-induced pneumonitis. Although the use of twice weekly oral methotrexate may have been a causative factor, a previously unsuspected drug interaction with etoposide may be the etiologic factor resulting in this unusually high incidence of pulmonary toxicity. The difficulty in establishing a diagnosis of interstitial pneumonitis in this group of patients with chronic lung disease and lung cancer is well known. The extent of morbidity and mortality seen in this study and the commercial availability of etoposide make earlier clinical recognition of this complication imperative.
在50例接受环磷酰胺、甲氨蝶呤和依托泊苷（VP - 16 - 213）治疗的小细胞未分化肺癌患者中，有12例（24%）出现间质性肺炎。所有12例患者的临床病程和病理特征均符合药物性肺炎。另有1例患者同时有间质性肺炎、肺孢子菌感染和血管周围转移的组织学证据。患者表现为严重呼吸困难、低氧血症、咳嗽、发热，胸部X线片显示双侧间质浸润。发病迅速且不可预测，治疗后短至1个月、长至5个月均可出现。9例患者康复，但急性期有3例直接死于药物性肺炎。虽然每周两次口服甲氨蝶呤的使用可能是一个致病因素，但与依托泊苷之前未被怀疑的药物相互作用可能是导致这种异常高的肺毒性发生率的病因。在这组患有慢性肺病和肺癌的患者中，诊断间质性肺炎存在困难，这是众所周知的。本研究中观察到的发病和死亡程度以及依托泊苷的商业可获得性使得早期临床识别这种并发症势在必行。
