Characteristics and outcomes of gemcitabine-associated pulmonary hypertension

Abstract

BackgroundDespite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying mechanism remains unclear.ObjectivesTo assess the association between gemcitabine and PH.MethodsWe identified incident cases of precapillary PH confirmed by right heart catheterisation in patients treated with gemcitabine from the French PH Registry between January 2007 to December 2022. The etiology, clinical, functional, radiologic, and hemodynamic characteristics of PH were reviewed at baseline and during follow-up. A pharmacovigilance disproportionality analysis was conducted using the WHO pharmacovigilance database.ResultsWe identified nine cases of PAH, either induced (in eight patients) or exacerbated (in one patient) by gemcitabine. Patients exhibited severe precapillary PH, with a median mean pulmonary arterial pressure of 40 (min-max 26–47) mmHg, a cardiac index of 2.4 (1.6–3.9) L·min−1·m−2, and pulmonary vascular resistance of 6.3 (3.1–12.6) WU. The median time from the initiation of gemcitabine to the onset of PH was 7 (4–50) months, with patients receiving a median of 16 (6–24) gemcitabine injections. Six patients showed clinical improvement upon discontinuation of gemcitabine. In the WHO pharmacovigilance database, we identified a significant signal with 109 cases reporting at least one adverse event related to PH with gemcitabine.ConclusionBoth clinical cases and pharmacovigilance data substantiate a significant association between gemcitabine use and the onset or worsening of precapillary PH. The observed improvement following the discontinuation of treatment underscores the importance of PH screening in gemcitabine-exposed patients experiencing unexplained dyspnea.