Aspergillosis superinfection as a cause of death of crizotinib-induced interstitial lung disease successfully treated with high-dose corticosteroid therapy

Abstract

Crizotinib is an efficacious and well-tolerated drug in the management of ALK-positive lung cancer. Crizotinib treatment, however, is rarely complicated by the occurrence of acute interstitial lung disease (ILD) that is often fatal. There is no treatment for this serious adverse event. We report a female non-small cell lung cancer patient who developed ILD after a few days of crizotinib therapy. She showed a significant improvement after a high dose of pulse corticosteroid therapy, both radiologically and clinically. Unfortunately, the patient subsequently developed an aspergillosis superinfection leading to death. Our experience suggests that high-dose steroid therapy may be efficacious in the management of a severe complication of crizotinib therapy. However, potent antifungal therapy should be considered to prevent the risk of severe aspergillosis.

Keywords: Acute interstitial lung disease; Crizotinib; Non-small cell lung cancer.

Fig. 1

a The tumor lesion before crizotinib administration was mainly necrotic with air-fluid level and had a diameter of about 41 mm, ilo-perihilar right. b After 10 days of crizotinib administration, a CT scan of the chest showed extensive bilateral ground-glass opacities throughout both lungs and a further increase in the solid lesion (excavated), which measured about 60 mm. c After treatment with corticosteroid, a reduction of the ground-glass component occurred bilaterally, while the lesion in the right lower lobe appeared essentially unchanged in morphology and size.

Fig. 2

Diffuse invasive aspergillosis observed in autopsy lung tissue (HE ×400).