Journal of Clinical Oncology, Vol 19, Issue 5
(March), 2001: 1444-1454
© 2001 American Society for Clinical Oncology
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
By Gerald Batist,
Gopal Ramakrishnan,
Chandra Sekhar Rao,
Aruna Chandrasekharan,
John Gutheil,
Troy Guthrie,
Pankaj Shah,
Ali Khojasteh,
Madhavan Krishnan Nair,
Karen Hoelzer,
Katherine Tkaczuk,
Youn Choi Park,
Lily W. Lee,
for the Myocet Study Group
From Jewish General Hospital, McGill University, Montreal, Quebec, Canada; Tata Memorial Hospital, Mumbai; MNJ Institute of Oncology, Hyderabad; Cancer Institute, Madras; The Gujarat Cancer and Research Institute, Ahmedabad; Regional Cancer Centre, Trivandrum, India; Sidney Kimmel Cancer Center, San Diego, CA; University Medical Center, Jacksonville, FL; Columbia Comprehensive Cancer Clinic, Columbia, MO; Springfield Clinic, Springfield, IL; University of Maryland Cancer Center, Ellicott City, MD; and The Liposome Company, Princeton, NJ.
Address reprint requests to Gerald Batist, MD, Jewish General Hospital, 3755 Cote St Catherine, Montreal, PQ H3T 1E2, Canada; email: gbatist{at}onc.jgh.mcgill.ca
PURPOSE: To determine whether Myocet (liposome-encapsulated doxorubicin; The Liposome Company, Elan Corporation, Princeton, NJ) in combination with cyclophosphamide significantly reduces doxorubicin cardiotoxicity while providing comparable antitumor efficacy in first-line treatment of metastatic breast cancer (MBC).
PATIENTS AND METHODS: Two hundred ninety-seven patients with MBC and no prior chemotherapy for metastatic disease were randomized to receive either 60 mg/m2 of Myocet (M) or conventional doxorubicin (A), in combination with 600 mg/m2 of cyclophosphamide (C), every 3 weeks until disease progression or unacceptable toxicity. Cardiotoxicity was defined by reductions in left-ventricular ejection fraction, assessed by serial multigated radionuclide angiography scans, or congestive heart failure (CHF). Antitumor efficacy was assessed by objective tumor response rates (World Health Organization criteria), 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 doxorubicin dose at onset was more than 2,220 mg/m2 for MC versus 480 mg/m2 for AC (P = .0001, hazard ratio, 5.04). MC patients also experienced less grade 4 neutropenia. Antitumor efficacy of MC versus AC was comparable: objective response rates, 43% versus 43%; median time to progression, 5.1% versus 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 significantly reducing cardiotoxicity and grade 4 neutropenia and provides comparable antitumor efficacy, when used in combination with cyclophosphamide as first-line therapy for MBC.
Presented in part at the Thirty-Fifth Annual Meeting of the American Society of Clinical Oncology, Atlanta, GA, May 15-18, 1999.
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