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mTOR inhibitor-induced interstitial lung disease in cancer patients

mTOR inhibitors have clinically significant activity against various malignancies, such as renal cell carcinoma and breast cancer, but their use can be complicated by several toxicities.
Interstitial lung disease ( ILD ) is an adverse event of particular importance. Mostly, mTORi-induced interstitial lung disease remains asymptomatic or mildly symptomatic, but it can also lead to severe morbidity and even mortality. Therefore, careful diagnosis and management of interstitial lung disease is warranted.

The reported incidence of mTORi-induced interstitial lung disease varies widely as because of a lack of uniform diagnostic criteria and active surveillance. Due to the nonspecific clinical features, a broad differential diagnosis that includes ( opportunistic ) infections should be considered in case of suspicion of mTORi-induced interstitial lung disease.

The exact mechanism or interplay of mechanisms leading to the development of interstitial lung disease remains to be defined. Suggested mechanisms are either a direct toxic effect or immune mediated mechanisms, considering mTOR inhibitors have several effects on the immune system.

The clinical course of interstitial lung disease varies widely and is difficult to predict. Consequently, the discrimination between when mTOR inhibitors can be continued safely and when discontinuation is indicated is challenging. ( Xagena )

Willemsen AE et al, Int J Cancer 2015; Epub ahead of print