Epirubicin and paclitaxel with G-CSF support in first line metastatic breast cancer: a randomized phase II study of dose-dense and dose-escalated chemotherapy.

An increased dose-intensity can be achieved by either higher dose of chemotherapy per cycle (dose-escalation) or by shortening the interval between cycles (dose-dense). This multicenter randomized phase II study assessed the efficacy and safety of two different approaches: epirubicin 110 mg/m(2) combined with paclitaxel 200 mg/m(2) every 21 days and epirubicin 75 mg/m(2) combined with paclitaxel 175 mg/m(2) every 10 days, both supported with G-CSF. Patients with advanced breast cancer and without prior palliative chemotherapy were scheduled for 6 cycles. Evaluable for response were 101 patients and for toxicity 106 patients. Grade ≥ 3 toxicities occurred in 39% of patients in the dose-escalated arm and in 29% of the dose-dense arm, mainly febrile neutropenia, thrombocytopenia, neurotoxicity and (asymptomatic) cardiotoxicity. The median delivered cumulative doses for epirubicin/paclitaxel were 656/1194 and 448/1045 mg/m(2), treatment durations were 126 and 61 days, and delivered dose intensities were 36/67 and 51/120 mg/m(2)/week for the dose-escalated and dose-dense arm, respectively. Response rates were 75 and 70%, the progression-free survival 6 and 7 months, respectively. Dose-dense chemotherapy with a lower cumulative dose, a halved treatment time, but a higher dose-intensity may be as effective and safe as dose-escalated chemotherapy. The value of dose-densification over standard scheduled chemotherapy regimes yet needs to be determined.

Echocardiographic diagnosis in carcinoid heart disease.

In this case report the typical echocardiographic features of carcinoid heart disease are presented. Newer treatments such as the use of a somatostatin analogue, interferon and hepatic de-arterialisation have improved the prognosis in patients with carcinoid syndrome. Nevertheless this syndrome portends a poor prognosis in patients with cardiac involvement. Cardiac lesions are mainly located in the right side of the heart. Regurgitation and stenosis of the tricuspid and pulmonary valve, leading to right heart failure, are the most common cardiac manifestations of the disease. Elevated levels of serotonin are probably responsible for the development of these cardiac lesions. Despite treatment resulting in significant reductions of urinary levels of 5-HIAA, regression of the cardiac manifestations in carcinoid syndrome has not been observed. Two-dimensional and Doppler echocardiography are the main tools to establish the diagnosis and severity of carcinoid heart disease. Cardiac surgery for carcinoid heart disease might improve symptoms and longevity, but the scarce data report on early mortality of over 35%.