Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer

Purpose: To determine whether Myocet (liposome-encapsulated doxorubicin; Th e Liposome Company, Elan Corporation, Princeton, NJ) in combination with cy clophosphamide significantly reduces doxorubicin cardiotoxicity while provi ding comparable antitumor efficacy in first-line treatment of metastatic br east cancer (MBC). Patients and Methods: Two hundred ninety-seven patients with MBC and no pri or chemotherapy for metastatic disease were randomized to receive either 60 mg/m(2) of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m(2) of cyclophosphamide (C), every 3 weeks until disease progressi on or unacceptable toxicity. Cardiotoxicity was defined by reductions in le ft-ventricular ejection fraction, assessed by serial multigated radionuclid e angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization c riteria) time to progression, and survival. Results: Six percent of MC patients versus 21% (including five cases of CHF ) of AC patients developed cardiotoxicity (P =.0002). Median cumulative dox orubicin dose at onset was more than 2,220 mg/m(2) for MC versus 480 mg/m(2 ) for AC (P =.0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of IMC versus AC was comparable: ob jective response rates, 43% versus 43%; median time to progression, 5.11% v ersus 5.5 months; median time to treatment failure, 4.6 versus 4.4 months; and median survival, 19 versus 16 months. Conclusion: Myocet improves the therapeutic index of doxorubicin by signifi cantly reducing cardiotoxicity and grade 4 neutropenia and provides compara ble antitumor efficacy, when used in combination with cyclophosphamide as f irst-line therapy for MBC, J Clin Oncol 19:1444-1454. (C) 2001 by American Society of Clinical Oncology.