Cancer Treatment Shows Efficacy in PAH Patients with Advanced Disease in Small Study

Cancer Treatment Shows Efficacy in PAH Patients with Advanced Disease in Small Study

An oral cancer treatment that works as a multi-kinase inhibitor, sorafenib, was seen to benefit patients with refractory, or treatment-resistant, advanced pulmonary arterial hypertension (PAH) in a small study in Japan.

The study was published in the journal Pulmonary Pharmacology & Therapeutics, in an article titled “Sorafenib as a Potential Strategy for Refractory Pulmonary Arterial Hypertension.

Sorafenib, under the brand name Nexavar, is a U.S. Food and Drug Administration-approved treatment for certain liver, kidney and thyroid cancers. It works by blocking, or inhibiting, the tyrosine and serine/threonine kinases, which are proteins that act as chemical messages to support cancer growth. PAH and cancer are known to share some pathological features and, for this reason, sorafenib is being investigated as a potential PAH treatment.

Tyrosine kinase and serine/threonine kinase have been associated with endothelial dysfunction, which can lead to pulmonary hypertension. In animal models of PAH, treatment with sorafenib was shown to improve pulmonary hypertension and prevent right heart remodeling. A Phase 1b study also found that sorafenib at 200 mg twice a day was safe for PAH patients.

Researchers at the Kyorin University School of Medicine investigated the efficacy and safety of sorafenib in treating refractory PAH. The study included nine patients, seven of whom had idiopathic PAH while the others had pulmonary veno-occlusive disease, a rare form of pulmonary hypertension. All had severe disease and showed signs of right heart failure.

Patient were given sorafenib as an add-on therapy to their current treatment regimen, at a dose of 50 or 100 mg a day, which was eventually increased to 100 to 400 mg/day. Changes in hemodynamic parameters, such as mean pulmonary arterial pressure and mean pulmonary vascular resistance, were compared at baseline and treatment’s end.

Results showed improvement in the New York Heart Association functional class, a measure of heart failure, in eight patients. Mean pulmonary arterial pressure decreased by between 14% and 28% in six patients, and mean pulmonary vascular resistance improved in four patients. The other patients did not show changes in these measures, and one withdrew from treatment.

Interestingly, beneficial changes in mean pulmonary arterial pressure were seen early in the treatment course, with little or no hemodynamic improvement until later, suggesting that sorafenib is best used “when started at an earlier stage,” the researchers wrote.

Indeed, they concluded: “The patients could only start taking sorafenib when they became seriously ill, because sorafenib is used on an off-label basis. This impli es that sorafenib may be more effective in improving symptoms and objective signs when it is started at an earlier stage. If the trial of sorafenib progresses with success, it should be started before patients become seriously ill.”

Some adverse effects were noted with sorafenib use in these patients. Five developed skin reactions to the drug on both their hands and feet, and for one of them, a systematic skin reaction was severe enough to stop the therapy.


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