Vici et al. Journal of Experimental & Clinical Cancer Research 2011, 30:39 http://www.jeccr.com/content/30/1/39 B A T Time (months) E: epirubicin; V: vinorelbine; PLD: pegylated liposomal doxorubicin Figure 1 Progression Free Survival. grade 3-4 neutropenic fever observed in 3 (5.5%) patients of arm A, and in 2 patients (4.0%) of arm B, in whom the administration of G-CSF was required. A 25% EPI/VNB dose-reduction was required in 7% of the patients, whereas a 25% PLD/VNB dose-reduction was required in 2 (4%) patients. Grade 3 thrombocytopenia was encoun- tered only in one patient in arm A. Grade 3 alopecia was universal in arm A, whereas in arm B it was of grade 3 only in 50% of the patients. Mild (G1-2) nausea and vomiting was encountered in 46.3%/44.0% of the patients in the two arms, respectively. Grade 3 mucositis was observed in 7.4% and 12% of the patients in arm A and B, respectively. Reversible AST/ALT elevation was reported in 2 patients in both arms, and mild and transient periph- eral neurotoxicity was observed in 8 and 7 patients in A A: EV B: PLD/V B Time (months) E: epirubicin; V: vinorelbine; PLD: pegylated liposomal doxorubicin Figure 2 Overall Survival. l a v i v r u S e e r F n o i s s e r g o r P l a v i v r u S l l a r e v O A: EV B: PLD/V Table 3 Grade 3-4 NCI-CTC toxicities in 104 enrolled patients Arm A (EV = 54) Arm B (PLD/V = 50) No. 4 11 - 1 2 6 3 25 1 - Page 5 of 8 % 8 22 - 2.0 4.0 12 6 50 2.0 - Anemia Neutropenia Thrombocytopenia Febrile neutropenia Hepatotoxicity Mucositis PPE/skin Alopecia Neurologic Cardiac No. 5 10 1 3 2 4 - 54 1 2 % 9.2 18.5 1.8 5.5 3.7 7.4 - 100 1.8 3.7 Abbreviations: NCI-CTC: National Cancer Institute Common Toxicity Criteria; PPE: palmoplantar erithrodysthesia; EV: epirubicin/vinorelbine; PLD/V: pegylated liposomal doxorubicin/vinorelbine arm A and B, respectively, while it was of grade 3 in 1 patients in both arms. Grade 3 PPE or cutaneous toxicity was observed in 3 (6%) patients of arm B, usually related to treatment duration, and prompted to treatment dis- continuation in 1 patient after 4 cycles. As cardiotoxicity concerns, no cases of congestive heart failure have been observed in the two arms. A transient and asymptomatic ≥ 20% LVEF decrease was encountered in 2 patients (3.7%) in arm A, and this prompted to treatment discon- tinuation after 5th, and 6th cycle; complete LVEF recov- ery was observed in two months. One case of transient and reversible supraventricular tachyarrhythmia was observed in arm A, during the last EPI infusion. The median cumulative delivered EPI dose was 540 mg/m2 (range, 90 to 720 mg/m2); the median cumulative deliv- ered PLD dose was 240 mg/m2 (range, 40 to 320 mg/m2). No toxic deaths have been observed in the two arms. Discussion Currently, there is no “gold standard” therapy for metastatic breast cancer, and treatment decisions must be based on patient and tumor characteristics, and on prior treatments. In 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 pre- treated 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 anthracycline-based regimen as first-line treatment for advanced disease, mostly in hormonal receptor and/or Her-2 negative tumors, where a “targeted” therapy is not available.