An Autopsy Case of Acute Pulmonary Toxicity Associated with Gemcitabine

Abstract

Acute respiratory distress syndrome (ARDS) developed following intravenous gemcitabine monotherapy in a 75-year-old man with non-small cell lung cancer. The total dose of gemcitabine was 1,500 mg, and the latent period from starting gemcitabine to pulmonary toxicity was three days. The chest radiographs and high resolution computed tomographic scan revealed bilateral groundglass opacity. He died on the fourteenth post-chemotherapeutic day due to respiratory failure. Postmortem examination of the lung revealed mixed exudative and fibrotic stages of diffuse alveolar damage. Pulmonary toxicity from gemcitabine can be acute and fatal.

Clinical features and correlates of gemcitabine‐associated lung injury

“…Finally, the taxonomy of gemcitabine-induced lung injury is imperfect. Published literature reports describe apparently similar presentations of gemcitabine-associated lung injury with the terms capillary leak syndrome, 24,26 -30 noncardiogenic pulmonary edema, 16,31,32 interstitial pneumonitis, 16,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] acute pneumonitis, 49 acute respiratory distress syndrome, 8,36,50,51 acute pulmonary toxicity, 52 or acute lung injury. 16,44,45,36,46,[53][54][55][56] In conclusion, our findings highlight the importance of consideration of the risk of lung injury from drug-drug or drug-radiotherapy interactions in designing novel therapeutic regimens for cancer patients, particularly for drugs with additive or synergistic pulmonary toxicity.…”

Gemcitabine Induced Pulmonary Toxicity with Late Onset

“…Generally it has simple side effects. These are; flu-like symptoms, nausea, vomitting and also bone marrow depression may be seen depending on the dosage (1)(2)(3)(4). First pulmonary toxicity is mentioned in 1997 (5).…”

“…Long term side effects are reported as interstitial covers (4). This time period is 3-4 months (3,4). As the clinical usage of gemcitabine increased, the side effects become more important.…”

“…But sometimes acute lung injury occurs (4,5,9,10). Some of them got better with high doses of corticosteroids but some of the patients died in short term (3,5,9). In autopsy studies, similar to other nucleoside analogs that acute lung damage shows a structural resemblance it is shown that with capillary leaks there were concentrated intraalveolar protein and noncardiogenic pulmonary edema with interstitial inflammation (3,7).…”

Pulmonary Toxicity due to Chemotherapy How is the Risk and Benefit from ZD1839 Treatment against Non-Small Cell Lung Cancer?

“…Gemcitabine is generally a well-tolerated chemotherapeutic agent and active against NSCLC. The spectrum of pulmonary toxicity after treatment with gemcitabine varies from mild dyspnea to a fatal acute respiratory syndrome as shown in the case report of Maniwa et al (1). Recently, the reports of life-threatening pulmonary injury associated with gemcitabine are increasing (4).…”