Pegylated liposomal doxorubicin (PLD) plus cyclophosphamide as 1st-line therapy for metastatic breast cancer in patients previously treated with anthracyclines

Abstract

745 Background: Anthracyclines are among the most active drugs used for the treatment of breast cancer. Utilization in advanced disease however, is limited by their intrinsic dose limiting cardio-toxicity and extensive exposure in the adjuvant setting. Pegylated Liposomal Doxorubicin (Caelyx/Doxil) has been shown to possess similar activity to conventional doxorubicin, with a more favorable toxicity profile and significantly less cardiotoxicity. Cyclophosphamide is commonly used in combination with anthracyclines, thus represents an interesting drug to use with PLD. Methods: We undertook a multi-center single arm phase II trial to assess the safety and efficacy of PLD 35mg/m2 in combination with cyclophosphamide 600 mg/m2 every 3 weeks. Eligibility criteria included: Measurable disease, prior anthracyclines exposure >12 months prior to study entry, adequate organ and bone marrow function. A 2 stage design was implemented with planned accrual of 70 patients if an objective response rate of ≥ 28% was observed in the first 25 patients in the absence of significant cardiac or other severe toxicities. Results: Previous adjuvant therapy included cyclophosphamide, doxorubicin, epirubicin, 5-Fu and taxanes in 90%, 59%, 41%, 30% and 27% of cases, respectively. Patients received a median of 4 cycles (4–10) of PLD and no major toxicity has been reported after the first 30 patients. Four patients experience asymptomatic >10% declines in LVEF that was reversible upon discontinuation of PLD. The incidence of hand foot syndrome (HFS) was relatively low (13%); only one patient stopped therapy due to grade 3 HFS. Other toxicities were uncommon and usually did not lead to discontinuation of therapy. An early efficacy analysis revealed a 32% objective response rate exceeding the predefined stopping rule. The study is now moving forward to the second stage. Conclusions: The combination of PLD with Cyclophosphamide given every 3 weeks is a safe and active combination in advanced breast cancer patients who relapse more then one year after completion of adjuvant therapy with anthracyclines. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Canada, Aventis, Pfizer, Roche Canada AstraZeneca, Aventis, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Hoffmann-La Roche, Novartis, Pfizer, Schering Amgen Canada, AstraZeneca, Aventis, Bristol-Myers Squibb, GlaxoSmithKline, Hoffmann-La Roche, Novartis, Pfizer