A multicenter randomized phase II study of nonpegylated liposomal doxorubicin plus vinorelbine versus nonpegylated liposomal doxorubicin plus cyclophosphamide as first line in locally advanced breast cancer (LABC) or metastatic breast cancer (MBC): Safety results

Abstract

1116 Background: We conducted a multicenter randomized phase II trial to assess activity and tolerability of the combination of nonpegylated liposomal doxorubicin plus vinorelbine versus standard nonpegylated liposomal doxorubicin plus cyclophosphamide. Methods: This multicenter randomized phase II study was planned to enrol 140 patients (pts). Elegibile pts must have LABC or MBC, PS (ECOG) ≤ 2, and measurable disease. Adjuvant or neoadjuvant chemotherapy with anthracyclines was allowed as well as prior endocrine therapy. Pts assigned to arm A received nonpegylated liposomal doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 on day 1 of a 21-day cycle. Pts assigned to arm B received nonpegylated liposomal doxorubicin 50 mg/m2 plus vinorelbine 25 mg/m2 iv on day 1, and 60 mg/m2 on day 8 po, every 3 weeks. The primary outcome measure was response rate (RR), whereas safety was one of the secondary endpoints. Results: Between July 2006 and July 2008 110 women were treated; for 80 of these, safety results are available. Patient characteristics: Arm A pts (N=41): median age, 59 (range 37–69); ER status ±/unk, 26/15/0; Her-2 status ±/unk, 5/34/2; PS 0/1/2, 26/14/1; prior adjuvant treatment with anthracyclines 10 pts (24%); dominant site of disease visceral 31 pts (76%). Arm B pts (N=39): median age, 61 (range 25–70); Er status ±/unk, 29/10/0; Her-2 status ±/unk, 3/35/1; prior adjuvant treatment with anthracyclines 14 pts (36%); dominant site of disease visceral in 28 pts (72%). There was no study discontinuation due to AE either in arm A or in arm B, nor study-related deaths. Conclusions: The combination regimen of nonpegylated liposomal doxorubicin plus vinorelbine appears to be associated with a slight increase of hematological and nonhematological toxicity when compared with nonpegylated liposomal doxorubicin plus cyclophosphamide. No increase in cardiotoxicity was seen. The trial is ongoing and we plan to give preliminary efficacy results at the time of the Meeting. [Table: see text] No significant financial relationships to disclose.