the scenario of patients presenting with advanced disease, still exists a subgroup who have received only endocrine adjuvant therapy, or adjuvant chemotherapy with CMF or CMF-like regimens and, less frequently, there is a small cohort treated with adjuvant taxanes-based or other anthracycline-free regimens; moreover, there are also anthracycline pretreated patients with a very long free-interval, to be considered still anthracycline sensitive. In all these patient cohorts there is still the option to employ an MEK162 molecular weight anthracycline-based regimen as selleck products first-line treatment for advanced disease, mostly in hormonal receptor and/or Her-2 negative tumors, where a “”targeted”" therapy is not available. The results of the present study confirm the activity of both anthracycline-based chemotherapy regimens for selleck kinase inhibitor anthracycline-naïve advanced
breast cancer patients, even if lower than expected. Response rate, progression free survival and overall survival observed in experimental arm B were comparable to those obtained in the “”calibration”" EPI/VNB arm. As toxicity concerns, both regimens were tolerable, with a higher incidence of febrile neutropenia and G3 alopecia in arm A, and of grade 3 mucositis and cutaneous toxicity in arm B. As cardiotoxicity concerns, the relatively low cumulative EPI dose delivered (≤ 720 mg/m2) did not allow to evidence significant clinical cardiotoxicity in the arm A, with only one case of arrhythmia, and a transient and asymptomatic in LVEF decrease occurring in 2 patients (3.7%), leading to a discontinuation of chemotherapy after 5 and 6 cycles, and with a complete recovery within two months. Analyzing literature data, the EPI/VNB regimen is among the active, non-taxane, anthracycline-containing combinations for breast cancer treatment, as confirmed by definite results of the Scandinavian Breast Trial Group , and other trials , but some instances of clinical
cardiac toxicity in terms of congestive heart failure or cardiomyopathy have been reported, with an incidence of asymptomatic LVEF decrease ranging from 20%-30% [33, 34], so there is an urgent need of introduce new active and safer regimens for anthracycline-sensitive Arachidonate 15-lipoxygenase breast cancer patients, and a recent metanalysis showed a significant lower rate of both clinical and subclinical heart failure in patients treated with liposomal anthracyclines, compared with conventional doxorubicin . A number of phase II trials have recently evaluated PLD in combination regimens with cyclophosphamide, paclitaxel, docetaxel, gemcitabine, VNB, and with biological agent such as trastuzumab or lapatinib, with response rates ranging from 31% to 75%, frequently occurring even in anthracycline pretreated patients , and with negligible cardiotoxicity.