Drug-induced pneumonitis in cancer patients treated with mTOR inhibitors: management and insights into possible mechanisms

Abstract

Introduction: Inhibitors of the mammalian target of rapamycin (mTOR) are widely utilized in cancer and transplantation, with increased use of these agents expected in future years. Although generally well tolerated, drug-induced pneumonitis (DIP) has been described as a class effect associated with these compounds, especially at higher doses. This toxicity is observed in about a third of cancer patients, although only around 10% will have symptoms necessitating treatment. Clinical DIP can be effectively managed by early recognition and prompt intervention, including dose reduction and/or treatment cessation. However, little is known about the pathophysiology of this entity and its best management.

Areas covered: This article will review current understanding of the mechanism of DIP, as well as the clinical impact and management of this toxicity in cancer patients treated with mTOR inhibitors. It also provides direction for future research.

Expert opinion: Although guidelines on the management of mTOR inhibitor-associated DIP in cancer patients have been published, these do not always concur or cover all management aspects. Education of patients and healthcare professionals is a key component in managing mTOR inhibitor therapy; assessing the history of pulmonary conditions before the initiation of such a therapy is also essential. Updated diagnostic criteria for pneumonitis might improve our knowledge in the future.

Keywords::

• drug-induced pneumonitis
• mammalian target of rapamycin inhibitors
• renal cell carcinoma
• tuberous sclerosis complex

Acknowledgments

The authors thank Noemi Espurz (Novartis) for her careful review of the manuscript.

Declaration of interest

The meeting was supported by an unrestricted educational grant from Novartis. The authors received writing/editorial support in the preparation of this manuscript provided by Marinella Calle, of Excerpta Medica, funded by Novartis. The authors did not receive honoraria related to the preparation of this manuscript, and were fully responsible for content and editorial decisions for this manuscript. I Duran has received consulting or lecture fees from Novartis and Pfizer. P-J Goebell has received consulting or lecture fees from Bayer, GlaxoSmithKline, Pfizer, Novartis, Amgen, Roche, Bristol-Myers Squibb, Janssen Cilag, Sanofi-Aventis and Hexal. K Papazisis has received consulting or lecture fees from Novartis, Bayer, GlaxoSmithKline, Pfizer, Amgen and Roche. A Ravaud is a member of global, European and/or French advisory boards for Pfizer, Novartis, GlaxoSmithKline, Bayer Schering, Bristol-Myers Squibb, Astellas and Aveo, has received travelling support from Pfizer and Novartis and has received institutional grant support from Pfizer, Novartis and Roche. T Weichhart has received grant support from Novartis and Pfizer. JA Rodriguez-Portal has received consulting fees from InterMune. K Budde has received research funds and/or honoraria from Pfizer, Novartis, Astellas, Roche, Hexal, Bristol-Myers Squibb, Veloxis Pharma and Siemens.

Notes

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