4, P = 0.001). Four I-BET-762 price patients developed congestive heart failure, 3 of them in the doxorubicin arm. The calculated mean cumulative dose

until cardiotoxicity occurrence was 580mg/m2 for doxorubicin and 780mg/m2 for the liposomal formulation (HR: 4.8, P = 0.001). A further Phase III study [36] randomized 160 patients to receive cyclophosphamide 600mg/m2 plus either epirubicin 75mg/m2 or liposomal doxorubicin 75mg/m2. No significant differences were observed in the rate of asymptomatic reduction in LVEF (11 versus 10%). In this study, no patient developed clinical heart failure. It must be noted Inhibitors,research,lifescience,medical that epirubicin dosing was lower than the equipotent doxorubicin. In 2010, the Cochrane Library reported a systematic review of the different anthracycline compounds Inhibitors,research,lifescience,medical and their cardiotoxicity [48]. Studies by Harris and Batist were analyzed together and authors concluded that nonpegylated liposomal anthracyclines reduced the overall risk of cardiotoxicity (RR = 0.38, P < 0.0001) and the risk of clinical heart failure (RR = 0.20, P = 0.02). Efficacy and safety Inhibitors,research,lifescience,medical of pegylated liposomal doxorubicin (PLD) combined with other cytostatic agents were studied in two Phase III studies. Sparano et al. [37] randomized 751 patients previously treated with anthracyclines (as adjuvant or neoadjuvant) with a PFI over 12 months to receive either docetaxel

75mg/m2 (373p) or the combination of PLD 30mg/m2 plus docetaxel 60mg/m2 every 21 days (378p) until disease progression or unacceptable toxicity occurred. Combined treatment improved PFS significantly from 7.0 to 9.8 months (HR 0.65; 95% CI, 0.55 −0.77; P < 0.00001). OS was similar: 20.6 months in the docetaxel arm and 20.5 in the combined treatment arm (HR 1.02; 95% CI, 0.86–1.22). The incidence of hand-foot syndrome Inhibitors,research,lifescience,medical was higher in the combined treatment arm (24% versus 0%) and symptomatic cardiac toxicity was similar: 4% in the docetaxel group and 5% in the PLD-docetaxel group. Patients with metastatic breast cancer progressing

after taxanes and anthracyclines had fewer treatment options Inhibitors,research,lifescience,medical and often anthracyclines were not used again, due to the cumulative risk of cardiotoxicity. Ketanserin Based on the safety and efficacy data for PLD, a Phase III study was proposed [49] in which 301 patients with metastatic breast cancer progressing to taxanes (<6 months) were randomized to receive one of the following three alternatives: PLD 50mg/m2 every 4 weeks (150p); vinorelbine 30mg/m2 every week (129p); or mitomycin-C 10mg/m2, on days, on 1 and 28 plus vinblastine 5mg/m2 on days 1, 14, 28, and 42 every 6–8 weeks (22p). 83% of patients had received prior anthracyclines, in 10% of them cumulative doses above 450mg/m2 had been reached. No patient treated with PLD showed clinical symptoms of cardiotoxicity. PFS was similar (2.86 months in the PLD group versus 2.53 months in the other two control groups) (HR 1.26; 95% CI, 0.98–1.62).