Pegylated liposomal doxorubicin (PLD) with cyclophosphamide (C) as 1^st-line chemotherapy for metastatic breast cancer (MBC) patients previously treated with adjuvant anthracyclines

Abstract

10627 Background: Anthracyclines (A) are key elements in adjuvant and metastatic chemotherapy regimens for breast cancer. Pre-exposure limits the utilization of A in advanced disease due to cumulative cardiotoxicity. PLD (Caelyx/Doxil) has equivalent activity to conventional doxorubicin in MBC. However PLD has reduced toxicity, including significantly less cardiotoxicity. Combinations of A+C are the backbone of many adjuvant therapies, thus C represents a logical drug to combine with PLD. Methods: MBC patients with measurable disease who completed anthracycline containing adjuvant therapy > 12 months ago were entered in a multi-center single arm phase II trial. They received PLD 35mg/m2 + cyclophosphamide 600 mg/m2 every 3 weeks. This study was powered to demonstrate an objective response rate > 25%. Results: Seventy three patients were enrolled. Prior adjuvant therapy included: AC (37%), CEF/FEC (28%), AC-T (15%), AT (7%), EC (7%). The median cumulative dose of prior A were 240mg/m2 and 580mg/m2 for doxorubicin or epirubicin, respectively. Median time since adjuvant chemotherapy was 4.4 years (1–14). Patients received a median of 6 cycles (2–10) of PLD + C. Major toxicities were; grade 3/4 neutropenia (7.5%), asymptomatic > 10% declines in LVEF (9%) (reversible upon discontinuation of PLD), grade 3/4 hand foot syndrome (6%). Other toxicities were uncommon and usually did not require discontinuation. The objective response rate (ORR) was 38% (4% CR and 34% PR), with an additional 32% having stable disease > 6 months for a clinical benefit of 70% (CB). ORR was similar for patients who had received adjuvant taxanes. Kaplan-Meyer estimated median time to progression was 31.5 weeks (23% progression free). Conclusions: The combination of PLD + C every 3 weeks in patients who have completed adjuvant anthracycline chemotherapy after more than one year prior is well tolerated and has a clinical benefit rate of 70%. This finding is similar to other commonly employed chemotherapeutic regimens for MBC and suggests that re-treatment with a non-cardiotoxic anthracycline following previous anthracycline therapy may be a reasonable therapeutic option for some patients. [Table: see text]

Liposomal Doxorubicin in Breast Cancer

“…The efficacy of PLD was further enhanced by combination with other chemotherapeutic agents that have different mechanisms of action and nonoverlapping toxicities. This has been documented in several studies in combination with cyclophosphamide [51,52], vinorelbine [53,54], gemcitabine [55,56], taxanes and trastuzumab [57,58,59]. The RRs range from 33–75%, which is higher than single agent-studies.…”