Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

International audienceThe combination therapy of doxorubicin and trastuzumab has been proven to be highly effective for metastatic breast cancer (MBC) patients with Her2/neu over-expressing tumors. However, this regimen is characterized by frequent cardiac toxicity, occurring in 27% of all treated patients and aggravating when the two substances are given concurrently. Pegylated liposomal doxorubicin (PLD) as a single agent reduces significantly cardiac toxicity and maintains efficacy compared to conventional doxorubicin. This prospective open labeled, multicenter phase II study assessed the potential cardiotoxicity and efficacy of PLD and trastuzumab as first and second line combination therapy in Her2/neu over-expressing MBC patients. Patients with Her2 over-expressing, measurable MBC with a baseline left ventricular ejection fraction (LVEF) ≥50% were treated with PLD 40 mg/m every 4 weeks for 6 up to 9 cycles and weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg). Cardiotoxicity was defined as the appearance of clinical signs or symptoms of congestive heart failure in combination with a decrease in LVEF ≤44% or ≥10 units below the normal value of 50% in the obligatory, subsequently performed transthoracic echocardiography. Due to conflicting interests, the planned accrual goal of 30 patients was not reached. Finally 16 patients were enrolled. Ten patients presented with more than one metastatic site and six of them were in second-line therapy. The median LVEF in the study cohort was 66.1 ± 8.68% at baseline, 62.7 ± 5.11% after 6 cycles of therapy, 64.4 ± 7.61% at the first follow up and did not change significantly (61.0 ± 5.56% even at the 5th follow-up). Six out of 12 assessable patients (50.0%) demonstrated a clinical benefit and after a median follow-up of 15.4 months a median progression free survival of 9.67 and a median overall survival of 16.23 months. Non-cardiac side effects were mild with only 3 CTC grade 3 events of 247 treatment cycles (1.2%) and no grade 4 toxicities. The combination of PLD and trastuzumab in patients with Her2/neu over-expressing metastatic breast cancer is a safe, feasible and effective therapy. However, cardiac function should be monitored at close intervals. Due to the promising clinical response rates and mild toxicity profile in this prognostically unfavorable group, this combination therapy should be evaluated in larger studies

Non-invasive imaging in the diagnosis of acute viral myocarditis

Autopsy series of consecutive cases have demonstrated an incidence of myocarditis at approximately 1–10%; on the contrary, myocarditis is seriously underdiagnosed clinically. In a traditional view, the gold standard has been myocardial biopsy. However, it is generally specific but invasive and less sensitive, mostly because of the focal nature of the disease. Thus, non-invasive approaches to detect myocarditis are necessary. The traditional diagnostic tools are electrocardiography, laboratory values, especially troponin T or I, creatine kinase and echocardiography. For a long period, nuclear technique with indium-111 antimyosin antibody has been used as a diagnostic approach. In the last years, the use of this technique has declined because of radiation exposure and 48-h delay in obtaining imaging after injection to prevent blood pool effect. Thus, a non-invasive diagnostic approach without radiation and online image availability has been awaited. Cardiac magnetic resonance imaging has these promising characteristics. With this technique, it is possible to analyse inflammation, oedema and necrosis in addition to functional parameters such as left ventricular function, regional wall motion and dimensions. Thus, cardiovascular magnetic resonance imaging has emerged as the most important imaging tool in the diagnostic procedure and the review focus on this field. But there are also advances in echocardiography and computer tomography, which are described in detail

Diagnosis of early myocarditis after respiratory or gastrointestinal tract viral infection: insights from cardiovascular magnetic resonance

BACKGROUND: The diagnosis of myocarditis continues to be a challenging task in clinical practice. The purpose of our study was to investigate cardiovascular magnetic resonance imaging in the diagnostic workup of ambulatory patients with the suspicion of early myocarditis after respiratory or gastrointestinal tract viral infection. The need for accurate diagnosis of early myocarditis arises from the low diagnostic accuracy of routine clinical tests. METHODS: We examined 67 consecutive patients with symptoms of weakness, palpitations, and fatigue after respiratory or gastrointestinal tract infection. We compared these patients to 31 controls. ECG-triggered, T2-weighted, fast-spin-echo triple inversion recovery sequences and delayed enhancement imaging were obtained in all patients, as well as functional parameters of left ventricular function and dimensions. In addition, in 25 patients and 10 controls, ECG-triggered, T1-weighted, multi-slice spin-echo images were obtained in axial orientation. RESULTS: We found a significant difference between patients with suspected myocarditis and controls in T2-global myocardial signal intensity. In addition, the ratio of global myocardial signal intensity/muscle signal intensity was 2.3 ± 0.4 in patients and 1.8 ± 0.3 in controls, which was highly significant (p < 0.001). In 23 patients, a pathological late enhancement pattern was seen, but only in one of the controls. There was no significant difference in T1-signal parameters. CONCLUSION: Cardiovascular magnetic resonance technique is able to detect early myocardial involvement after respiratory or gastrointestinal tract infection