Vici et al. Journal of Experimental & Clinical Cancer Research 2011, 30:39 http://www.jeccr.com/content/30/1/39 Page 6 of 8 The results of the present study confirm the activity of both anthracycline-based chemotherapy regimens for anthracycline-naïve advanced breast cancer patients, even if lower than expected. Response rate, progression free survival and overall survival observed in experimen- tal 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 feb- rile neutropenia and G3 alopecia in arm A, and of grade 3 mucositis and cutaneous toxicity in arm B. As cardio- toxicity concerns, the relatively low cumulative EPI dose delivered (≤ 720 mg/m2) did not allow to evidence sig- nificant clinical cardiotoxicity in the arm A, with only one case of arrhythmia, and a transient and asympto- matic 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 [33], and other trials [18], but some instances of clinical cardiac toxicity in terms of congestive heart fail- ure or cardiomyopathy have been reported, with an inci- dence 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 breast cancer patients, and a recent metanalysis showed a significant lower rate of both clinical and subclinical heart failure in patients treated with liposomal anthracy- clines, compared with conventional doxorubicin [35]. A number of phase II trials have recently evaluated PLD in combination regimens with cyclophosphamide, paclitaxel, docetaxel, gemcitabine, VNB, and with biolo- gical agent such as trastuzumab or lapatinib, with response rates ranging from 31% to 75%, frequently occurring even in anthracycline pretreated patients [36], and with negligible cardiotoxicity. In details, the PLD/ VNB combination was recently employed in two phase II trials in heavily pretreated patients, yielding a response rate of 36% and 39%, without any cardiac toxi- city [37,38]. Two more recent reports with PLD/VNB combination as first-line treatment in elderly patients confirmed the good overall clinical response rate (36% and 50%, respectively), and the high tolerability of the regimen [39,40] suggesting, due to the safety profile of the combination, the employment also in such “frail” patient population. An increasingly pertinent question in patients relap- sing following adjuvant anthracyclines is whether there is a role for anthracycline rechallenge in those with a long free-interval. As a result of a high cardiac risk asso- ciated with increasing cumulative anthracycline dose, patients are often denied re-treatment in advanced set- ting; the choice of a liposomal anthracycline allows the possibility of re-treating an anthracycline-responsive dis- ease without substantially increasing the cardiac risk [36]; this option should not be excluded in fact, and some evidences come from a recent report on first- line chemotherapy selection in adjuvant anthracycline- pretreated patients, where no differences have been found between CMF-based and anthracycline-containing regimens for their impact on the outcome of first-line anthracycline treatment [41]. By this point of view, even if our results are in anthracycline-naïve patients, the activity and the low toxicity profile observed suggest that the choice of a liposomal formulation can offer the chance of a more tolerable regimen maintaing con- ventional anthracyclines efficacy. The results of the present trial indicated both EPI/VNB and PLD/VNB as two reasonable choices as first-line treatment for women with relapsed breast cancer not previously treated with adjuvant anthracyclines; since advanced breast cancer is still an incurable disease, the goals of treatments are symptoms palliation with minimal toxicity, and survival prolongation, possibly with regi- mens active against cancer but also preserving patient’s quality of life; in this context, our results are encouraging, confirming the feasibility and efficacy of two anthracy- cline-containing regimens and, particularly, of a regimen devoided of cardiac toxicity and of other severe side effects, such as PLD/VNB; the choice of this combination could offer a better quality of life and, hopefully, a better outcome to metastatic breast cancer patients. Conclusions Both anthracycline-based regimens evaluated as first-line treatment in advanced breast cancer patients not pre- viously treated with anthracyclines seems to be active and well tolerated, and can be considered as a reason- able choice in this subset of patients Author details 1Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy. 2Department of Medical and Experimental Oncology, Oncologic Institute, Bari, Italy. 3Division of Medical Oncology, S. Francesco Hospital, Paola, Italy. 4Division of Surgery A, Regina Elena National Cancer Institute, Rome, Italy. 5Division of Gynecological Oncology, Regina Elena National Cancer Institute, Rome, Italy. 6Cardiologic Unit, Regina Elena National Cancer Institute, Rome, Italy. 7Biostatistics Unit, Regina Elena National Cancer Institute, Rome, Italy. Authors’ contributions PV, GC, ML designed the study; FG, DS, GF, PP, CB, EV, AC, LP, AL, LDL collected and assembled the data, DG performed the statistical analysis, PV and LDL wrote the manuscript. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests.