Low cardiotoxicity of nonpegylated liposomal doxorubicin (NPLD) in patients (pts) with metastatic breast cancer (MBC) previously exposed to 360 mg/m2 of doxorubicin (D).

Abstract

1112 Background: In pts with MBC, retreatment with chemotherapy agents given previously in the early disease setting is a valid therapeutic option. Re-introduction of anthracyclines is limited by the risk of accumulative cardiotoxicity. Since NPLD is less cardiotoxic, administration of NLPD could be a potential strategy to re-introduce anthracyclines in MBC. In order to explore this hypothesis, we have analyzed the cardiotoxicity NPLD-containing regimes in pts with MBC previously exposed to D 360 mg/m2. Methods: Pts had PS 0-2, basal left ventricular ejection fraction (LVEF) >50%, adequate organ function, and prior exposure of D in the (neo)adjuvant setting at a dose of 360 mg/m2. No prior liposomal anthracyclines were allowed. LVEF was measured before initiating treatment with NPLD and at least at the time of treatment discontinuation. Cardiac events were defined as type A in case of signs and/or symptoms of congestive heart failure plus grade 3/4 LVEF decline; or type B including asymptomatic LVEF decline, defined as an absolute drop ≥10% resulting in a final LVEF <50%, any absolute drop >20%, or LVEF <40%. Results: From 2004 to 2009 32 MBC pts who had received prior D 360 mg/m2, have been treated with NPLD-based therapy. Median prior number of chemotherapies regimens were 4 (2-9). Median cumulative dose of NPLD was 258 mg/m2 (range, 60-480) and the median number of cycles was 4 (1-8). Median LVEF at baseline was 60% declining to 54% after NPLD treatment, with a median LVEF decline of 5.75% (p< 0.001). No Type A cardiac events were observed. Type B events occurred in 9 pts (28.1%) with a delay in treatment due to LVEF decline in 6 of them (66.7%). Median time to progression was 3.06 months (95% CI 2.19-3.92) and median overall survival was 11.4 months (95% CI 8.12-13.96). Conclusions: NPLD administration in patients previously treated with D 360mg/m2 results in low cardiac toxicity and absence of type A (symptomatic) events. Our results are similar to that previously reported by our group in pts exposed to D at doses lower than 360 mg/m2 and suggest that NPLD is a valid option in pts with advanced disease that have progressed to approved agents. No significant financial relationships to disclose.