Purpose: Pegylated liposomal doxorubicin (PLD) is an active agent for breast cancer. The efficacy and safety of PLD in combination with cyclophosphamide as first-line treatment of metastatic breast cancer (MBC) was evaluated in this phase II study.
Patients and methods: Eligible patients had metastatic or recurrent breast cancer with no previous chemotherapy for metastatic disease. Patients were enrolled into 3 sequential cohorts: cohort I (n = 10) received PLD 50 mg/m2 intravenously (I.V.) on day 1 and cyclophosphamide 100 mg/m2 orally on days 1-14 every 28-day cycle; cohort II (n = 20) received PLD 30 mg/m2 plus cyclophosphamide 600 mg/m2 I.V. on day 1 every 21 days; and cohort III (n = 21) received PLD 35 mg/m2 plus cyclophosphamide 600 mg/m2 I.V. on day 1 every 21 days.
Results: An objective response was exhibited in 26 of 51 patients (4 complete responses [CRs], 22 partial responses [PRs]; 51%) in the intent-to-treat population and responses were similar among cohorts. The clinical benefit rate (CR plus PR plus stable disease) was 86%. The median duration of response was 35.1 weeks. The most common adverse events were nausea (71%), asthenia (69%), and neutropenia (67%). There was less toxicity in cohort II than in other cohorts. No clinical cardiac toxicity was observed. Only 2 of 20 patients in cohort II (10%) required treatment discontinuation as a result of adverse events.
Conclusion: First-line combination therapy with PLD and cyclophosphamide is active and well tolerated in patients with MBC. The recommended doses from this study are PLD 30 mg/m2 and cyclophosphamide 600 mg/m2 I.V. every 21 days.