Pavlakis N, Bell D R, Millward M J, Levi J A
Department of Clinical Oncology, Royal North Shore Hospital, St. Leonards, NSW, Australia.
Cancer. 1997 Jul 15;80(2):286-91. doi: 10.1002/(sici)1097-0142(19970715)80:2<286::aid-cncr17>3.0.co;2-q.
Pulmonary toxicity reported with gemcitabine is usually mild and self-limiting. The authors report a series of three patients who had life-threatening pulmonary toxicity after receiving gemcitabine.
The three patients presented to two major teaching hospitals with significant pulmonary dysfunction while receiving gemcitabine. Case data were obtained from patient records. A review of the literature was done to seek reports of pulmonary toxicity with gemcitabine and cytosine arabinoside (ara-C).
The common features of the respiratory illnesses of the three patients in this study were tachypnea, marked hypoxemia, and an interstitial infiltrate on chest radiograph consistent with pulmonary edema. There was no evidence of underlying heart disease in any patient. In addition, there was no evidence of infection, metabolic causes, or lymphangitic carcinomatosis to explain the clinical findings. Two patients died, and postmortem examination confirmed acute RDS (respiratory distress syndrome), whereas in the third patient a transbronchial biopsy showed interstitial pneumonitis. These findings were consistent with drug-induced pulmonary toxicity. Diuretics and corticosteroids were useful measures for treating the patients' symptoms, and one patient survived after gemcitabine was withdrawn.
These three cases of acute RDS may be the result of a capillary leak phenomenon due to treatment with gemcitabine, as observed in patients given intermediate dose and high dose ara-C, a drug similar in structure and metabolism to gemcitabine. The authors suggest caution in repeated administration of gemcitabine to patients who develop unexplained noncardiogenic pulmonary edema. Withdrawing gemcitabine and administering corticosteroids and diuretics may help to avert a fatal outcome.
吉西他滨所致的肺部毒性通常较轻且具有自限性。作者报告了3例患者在接受吉西他滨治疗后出现危及生命的肺部毒性。
这3例患者在接受吉西他滨治疗期间因严重的肺功能障碍就诊于两家大型教学医院。病例数据来自患者记录。对文献进行回顾以查找有关吉西他滨和阿糖胞苷（ara-C）所致肺部毒性的报告。
本研究中3例患者呼吸系统疾病的共同特征为呼吸急促、明显低氧血症以及胸部X线片上与肺水肿一致的间质浸润。所有患者均无潜在心脏病证据。此外，没有证据表明感染、代谢原因或淋巴管癌转移可解释这些临床表现。2例患者死亡，尸检证实为急性呼吸窘迫综合征（RDS），而第3例患者经支气管活检显示为间质性肺炎。这些发现与药物性肺毒性相符。利尿剂和皮质类固醇对治疗患者症状有效，1例患者在停用吉西他滨后存活。
这3例急性RDS可能是由于吉西他滨治疗引起的毛细血管渗漏现象所致，正如接受中剂量和高剂量阿糖胞苷治疗的患者中所观察到的那样，阿糖胞苷在结构和代谢上与吉西他滨相似。作者建议，对于出现不明原因的非心源性肺水肿的患者，在重复给予吉西他滨时应谨慎。停用吉西他滨并给予皮质类固醇和利尿剂可能有助于避免致命后果。
