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Curr Opin Pulm Med. 2017 Sep;23(5):392-397. doi: 10.1097/MCP.0000000000000412.

Pulmonary arterial hypertension induced by tyrosine kinase inhibitors.

Author information

1
aDivision of Respirology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada bUniversité Paris-Sud, Faculté de Médecine, Université Paris-Saclay cAP-HP, Service de Pneumologie, Centre de Référence de l'Hypertension Pulmonaire Sévère, Hôpital Bicêtre, Le Kremlin-Bicêtre dINSERM UMR_S 999, Hôpital Marie Lannelongue, Le Plessis Robinson eUniversité Paris-Sud, Faculté de Pharmacie, Université Paris-Saclay, Châtenay Malabry fAP-HP, Service de Pharmacie, DHU-TORINO, Hôpital Antoine Béclère, Clamart, France.

Abstract

PURPOSE OF REVIEW:

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of several neoplastic conditions; however, pulmonary arterial hypertension (PAH) has been reported as a complication of TKIs, predominantly with dasatinib. Recent studies have elucidated the potential mechanisms of TKI-induced PAH and have better clarified the long-term outcomes.

RECENT FINDINGS:

In addition to the known association between dasatinib and PAH, several other TKIs have recently been reported to cause PAH, including ponatinib, bosutinib and lapatinib. Dasatinib causes direct pulmonary artery endothelial cell toxicity through the production of mitochondrial reactive oxygen species, but likely requires the presence of a second risk factor to cause PAH. Symptoms and haemodynamic abnormalities frequently resolve after discontinuation of the TKI, but PAH persists in over a third of patients and can reoccur when other TKIs are used, which warrants close follow-up. Rare fatal cases have occurred; therefore, treatment with PAH-specific therapy is recommended for patients with right heart failure or persistent PAH after discontinuation of the TKI.

SUMMARY:

PAH is a rare but important complication of several TKIs. Management includes discontinuation of the TKI, close follow-up and PAH-specific therapy in severe cases.

PMID:
28639957
DOI:
10.1097/MCP.0000000000000412
[Indexed for MEDLINE]

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