Evaluation of treatment with bosentan in patients with carcinoid heart disease: single center study.

BACKGROUND: The primary aim of this study was to evaluate a combined therapeutic intervention, including the dual endothelin receptor antagonist bosentan, in patients with carcinoid heart disease (CaHD). The efficacy of the treatment protocol was investigated using serological, echocardiographic, and clinical markers. PATIENTS AND METHODS: Since 2003, 40 patients with neuroendocrine tumours were identified; 14 had echocardiographic findings consistent with CaHD. Six of the 14 patients with CaHD and a New York Heart Association (NYHA) functional class >or= III received bosentan and were eligible for inclusion in this study. RESULTS: N-terminal pro-brain natriuretic peptide (NT-pro-BNP) had decreased 6 months after treatment with bosentan (median: 646 pg/ml vs. 400.5 pg/ml; p = 0.02); the right ventricular systolic pressure had decreased after 3 and 6 months (median: 69 mmHg vs. 61 mmHg, p = 0.02; median: 69 mmHg vs. 48.5 mmHg, p = 0.02); the 6-minute walk distance (6MWD) had significantly improved after 3 and 6 months of treatment (median: 293.5 vs. 406.5 m; p = 0.02; median: 293.5 vs. 578.5 m; p = 0.02). The NYHA functional class improved in 5/6 patients receiving bosentan. CONCLUSIONS: Combined treatment with bosentan is effective in patients with CaHD, based on functional class, 6MWD, and NT-pro-BNP. Further clarification of the CaHD fibrosis pathogenesis is needed to facilitate development of targeted antifibrotic therapeutic agents.

Neoplastic pericardial disease in lung cancer: impact on outcomes of different treatment strategies. A multicenter study.

BACKGROUND: Local (intrapericardial) chemotherapy has been reported to be useful for the treatment of neoplastic pericardial disease, but it has never been compared to systemic chemotherapy, a combination of the two and simple pericardial drainage or sclerosis. METHODS: We analyzed the clinical and echocardiographic data of 119 patients, suffering of neoplastic pericarditis due to lung cancer (97 with non-small-cell), comparing the outcomes of four different treatment strategies (extended catheter drainage/sclerosis, systemic chemotherapy, local chemotherapy, and combined - local plus systemic - chemotherapy) at the last available follow-up or at the change of therapy after a treatment failure. The outcomes (based on semiquantitative evaluation of pericardial disease) were classified as complete, partial, no response and progressing disease. RESULTS: A complete response was achieved in 37/53 of patients with combined, in 12/22 with local, in 5/27 with systemic chemotherapy, respectively, and in 4/17 after drainage/sclerosis (p<0.001). Overall response was achieved in 51/53 with combined, 18/22 and 16/27 with local or systemic chemotherapy, respectively, and in 5/17 with drainage/sclerosis only (p<0.001). Survival was significantly better after combined chemotherapy (p<0.001) and 12/53 patients (23%) in this subgroup survived more than 1 year. The overall response rate was higher with intrapericardial cisplatinum than with other agents (98% vs 80%, χ(2)=7.69, p<0.01). CONCLUSIONS: Local chemotherapy, alone or with systemic chemotherapy, is effective in treating pericardial metastases from lung carcinoma, leading to a good control of pericardial effusion in 92% of cases, and to complete disappearance of effusion and masses in 65%. Combined therapy is significantly better than any other treatment. Pericardiocentesis and intrapericardial chemotherapy should be used whenever possible in lung cancer neoplastic pericardial disease, not only in case of tamponade.

Intrapericardial cisplatin administration after pericardiocentesis in patients with lung adenocarcinoma and malignant cardiac tamponade.

INTRODUCTION: Patients with lung adenocarcinoma often suffer from metastatic pericardial effusion that may eventually cause cardiac tamponade. Recurrence of pericardial effusion is frequent after pericardial drainage and therapy for the prevention of fluid reaccumulation is still controversial. We evaluated the safety and effectiveness of the intrapericardial infusion of cisplatin, a substance with antineoplastic and sclerosing properties, after pericardiocentesis in patients with lung adenocarcinoma and malignant cardiac tamponade. METHODS: Twenty-five patients (19 males and 6 females, median age 55 years) with lung adenocarcinoma confirmed by cytological examination and cardiac tamponade were studied. All patients underwent subxiphoid pericardiocentesis through catheter insertion, under electrocardiographic, echocardiographic and haemodynamic guidance. After the malignant aetiology of the pericardial effusion had been confirmed by cytological examination, cisplatin was instilled (10 mg in 20 ml normal saline) into the pericardial cavity during three consecutive days. Clinical and echocardiographic evaluation was performed every month thereafter. RESULTS: Pericardial fluid of 350-1700 ml was removed (median 750 ml) and was haemorrhagic in 80% of the cases. Paroxysmal atrial fibrillation was detected in three patients (12%) and non-sustained ventricular tachycardia in two (8%). None of the patients had hypotension or retrosternal pain. One patient suffered from significant pericardial effusion reaccumulation (4%). Laboratory findings were not influenced by systemic drug absorption in any patient. Transthoracic echocardiographic study revealed pericardial thickening without physiology of constriction in 4 patients (16%). After pericardiocentesis, the mean survival period overall was 4.5 months (range 3-92 weeks), and mortality was attributed to widespread disease (respiratory failure). CONCLUSIONS: Intrapericardial administration of cisplatin is safe and effective in preventing the reaccumulation of malignant pericardial effusion in the majority of patients with lung adenocarcinoma.