Pegylated liposomal doxorubicin and cyclophosphamide as first-line therapy for patients with metastatic or recurrent breast cancer.

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.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.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.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.