Sorafenib as a potential strategy for refractory pulmonary arterial hypertension.
Sorafenib is an inhibitor of multi-kinases including tyrosine and serine/threonine kinases. We investigated the efficacy and safety of sorafenib for the treatment of patients with refractory pulmonary arterial hypertension (PAH). Sorafenib was started in 9 patients (7 with idiopathic PAH, 2 with pulmonary veno-occlusive disease) who had severe PAH and right heart failure, in spite of treatment with vasodilators specific for PAH. Sorafenib was started as an add-on therapy at a dose of 50 or 100 mg/day, and increased to 100-400 mg/day. New York Heart Association functional class improved in 8 patients and did not change in 1. Mean pulmonary arterial pressure improved in 6 patients (14-28% decrease) and did not apparently change in 2 (follow-up catheterization was not performed in 1 patient). The main adverse effects of sorafenib were skin reactions on the hands and feet, which appeared in 5 patients. They were tolerable in 4 patients, but discontinuation of sorafenib was needed in only 1 patient. In conclusion, sorafenib had favorable effects to improve symptoms and objective variables in patients with refractory PAH, with tolerable adverse events. Sorafenib is an alternative strategy for patients with refractory PAH.
Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Gou
G
Kimura
Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan; Department of Cardiology, Keio University School of Medicine, Tokyo, Japan. Electronic address: m.kataoka09@keio.jp.
Masaharu
M
Kataoka
Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Takumi
T
Inami
Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
Keiichi
K
Fukuda
Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.
Hideaki
H
Yoshino
Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan. Electronic address: tsatoh@ks.kyorin-u.ac.jp.
Toru
T
Satoh
D000293:Adolescent; D000328:Adult; D062186:Arterial Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D065627:Familial Primary Pulmonary Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D010671:Phenylurea Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D012720:Severity of Illness Index; D000077157:Sorafenib; D016896:Treatment Outcome
D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
Multi-kinase inhibitor; Pulmonary arterial hypertension; Pulmonary veno-occlusive disease; Right heart failure; Sorafenib