Originally published as JCO Early Release 10.1200/JCO.2005.03.8331 on May 8 2006

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Pegylated Liposomal Doxorubicin and Trastuzumab in HER-2 Overexpressing Metastatic Breast Cancer: A Multicenter Phase II Trial

Stephen Chia, Mark Clemons, Lee-Ann Martin, Angela Rodgers, Karen Gelmon, Gregory R. Pond, Lawrence Panasci

From the British Columbia Cancer Agency, Vancouver Cancer Centre; British Columbia Cancer Agency, Fraser Valley Cancer Centre, Surrey BC; Toronto Sunnybrook Regional Cancer Centre; Princess Margaret Hospital, Toronto, Ontario; Schering Canada Inc; and McGill University, Jewish General Hospital, Montréal, Québec, Canada

Address reprint requests to Stephen Chia, MD, British Columbia Cancer Agency, Vancouver Cancer Centre, 600 W 10th Ave, Vancouver, BC, Canada V5Z 4E6; e-mail: schia{at}bccancer.bc.ca

PURPOSE: Cardiotoxicity precludes the concurrent use of doxorubicin and trastuzumab. Because pegylated liposomal doxorubicin (PLD) has equal efficacy but significantly less cardiotoxicity than conventional doxorubicin, this phase II study assessed the rate of cardiotoxicity and efficacy of first-line PLD plus trastuzumab in HER-2–positive metastatic breast cancer (MBC).

PATIENTS AND METHODS: Women with HER-2–positive, measurable MBC, and a baseline left ventricular ejection fraction (LVEF) 55% were treated with PLD 50 mg/m² every 4 weeks for six cycles and weekly trastuzumab (4 mg/kg loading dose then 2 mg/kg thereafter). Cardiotoxicity was defined as symptomatic congestive heart failure (CHF) with 10% decline in LVEF to below lower limits of normal, 15% decline in LVEF without symptomatic CHF, or less than 10% LVEF decline to less than 45%.

RESULTS: Thirty women were enrolled, 13 had received prior adjuvant anthracyclines. A median 5.5 cycles of PLD were administered. Mean baseline LVEF was 62.8%, 59.5% after cycle four, and 58.3% after cycle six. Three patients (10%) developed protocol-defined cardiotoxicity. No patients developed symptomatic CHF. Response rate was 52%, with an additional 38% stable disease rate. At a median follow-up of 13.9 months, the median progression-free survival was 12.0 months; median overall survival has not yet been reached. The most common adverse events were grade 3 hand-foot syndrome (30%) and grade 3/4 neutropenia (27%).

CONCLUSION: The combination of PLD and trastuzumab is a well tolerated and active regimen in HER-2-positive MBC. Cardiotoxicity was observed, but limited to asymptomatic declines in LVEF. Further evaluation of this combination is warranted.

Supported by Schering Plough and Hoffmann La-Roche.

Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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