Safety and activity of nonpegylated liposomal doxorubicin (nPLD) combined with oral metronomic cyclophosphamide (mC) as preoperative treatment for locally advanced breast cancer (BC) patients (pts).

Abstract

e11546 Background: nPLD has the same clinical benefits but less toxicity than the traditional doxorubicin. It’s well reported mC produces anti-proliferative and anti-angiogenic effect in tumours. We conducted a retrospective study to evaluate the safety and activity of the association of nPLD and mC in pts with locally advanced BC. Methods: A total of 41 female pts with HER2-negative locally advanced BC unfit for standard chemotherapy received nPLD 25 mg/mq biweekly for eight courses along with mC 50 mg daily as primary systemic treatment. Toxicity and clinical-radiological response with Ki67 and CD31 expression were evaluated in tumour specimens obtained before and after treatment. Results: Pts characteristics included: median age 47.5 years; 31.7% Luminal A (LA), 56.1% Luminal B (LB), and 12.2% Triple Negative BC subtype classified by immunohistochemistry. The rate of breast-conserving surgery was 59.5%. All pts were evaluable for response. Objective response rate (ORR) was 58.5% (95% confidence interval, 42.1% to 73.7%), with 4 (9.7%) clinical complete responses (CR) and 20 (48.8%) partial responses. Sixteen pts (39.0%) achieved a stable disease and 1 pt progressed. One pt experienced a pathological CR. LA subtype was significantly associated with better ORR than others subtypes (p=0.049) and especially than LB (p=0.040). There was a borderline significant reduction of Ki67 expression after treatment (median, 15.5% to 9%; p=0.056), but no significant variation in CD31 expression (p=0.865). The majority of adverse events (AEs) were mild or moderate. Grade ≥3 AEs included neutropenia (12.2%), vomiting (4.9%) and hyperglycemia (2.44%). Temporary treatment suspension due to toxicity occurred in 8 (19.5%) pts; discontinuation was necessary in 1 pt. No symptoms were related to impairment of cardiac function. Mean left ventricular ejection fraction levels did not change substantially before and after treatment: 58.7% and 57.1%, respectively. Conclusions: The combination of nPLD and mC is well tolerated, with a promising activity as preoperative therapy in unfit pts with locally advanced BC.