Reversible heart failure after sorafenib administration in advanced metastatic differentiated thyroid carcinoma (DTC)
Massimo Giusti1, Maria Derchi2, Lorenzo Mortara1, Mario Canepa2, Francesca Cecoli1, Francesco Minuto1 & Paolo Spallarossa2
Sorafenib (S) is a reasonably well-tolerated therapy in DTC. A large number of side-effects have been reported. We report our data on the effectiveness and tolerability of S in 6 patients with advanced metastatic epithelial (2 follicular, 1 papillary, 1 insular) and medullary DTCs (5279 years). In all patients, heart function was evaluated before and during S administration (400 mg/day) together with the objective response rate and changes in serum markers. Underlying heart function, clinical examination, EKG, echocardiographic assessment and N-terminal type-B natriuretic peptide (NT-proBNP) and troponin I levels were recorded before therapy, on therapy and after S discontinuation. Hypertension was found in 50% of patients before therapy; in these patients, hypotensive treatment did not change on therapy. In 2 of the remaining patients, hypotensive therapy was started after a 1-month period of S. S therapy was discontinued in 3 cases owing to: disease progression after a 6-month period of stable disease; patient request due to mucositis and skin rash after 3 months; and severe heart failure (NYHA class 4) after 3 months. No patients showed changes in troponin I levels. NT-proBNP levels sharply increased in a previously normotensive patient with insular cancer after 2 months on S, when heart failure begun. A slight NT-proBNP increases was seen in 2 further subjects. The table reports some of the echo-cardiographic variables measured. In case 4, heart function returned to pre-S levels in the 6-month after S discontinuation and BP normalized on hypotensive therapy.
Our data seem to indicate a decrease in tumor markers and a partial response in 66% of subjects during a 36 month course of S. Hypertension and severe heart failure may occur but they are not associated with cardiomyocyte death and are reversible side-effects. Heart function should be carefully monitored during S therapy in thyroid cancer patients.