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Less Cardiotoxicity With Liposomal Doxorubicin

Less Cardiotoxicity With Liposomal Doxorubicin

MONTREAL—Single-agent therapy with liposomal doxorubicin matched the response rate of conventional doxorubicin in patients with metastatic breast cancer but caused less toxicity, especially cardiotoxicity, Gerald Batist, MD, reported at the San Antonio Symposium.

Treatment with the liposomal formulation (Evacet, The Liposome Company, Princeton, NJ) led to a 28% response rate vs 25% with free doxorubicin. Protocol-defined cardiotoxicity occurred in twice as many patients treated with free doxorubicin, 27% vs 13%. Dr. Batist characterized the 28% and 25% response rates as acceptable for single-agent therapy. He noted that results of a study of Evacet plus cyclophosphamide vs free doxorubicin plus cyclophosphamide showed identical response rates and disease-free survival “with much less cardiotoxicity in the Evacet group.”

Future Uses

“In the future, Evacet could have a tremendous role to play in the treatment of breast cancer,” said Dr. Batist, of McGill University. “First, in the adjuvant setting, I think the use of the agent is a highly rational approach. Second, we have seen striking examples of drugs and novel agents that appear to represent steps forward in breast cancer therapy, except for cardiotoxicity. Obviously, there is work to be done with the combination of Evacet and some of these new agents.”

Dr. Batist reported findings from 224 evaluable patients from a total of 288 randomized to liposomal or free doxorubicin. Each group received 75 mg/m² of doxorubicin as a 60-minute infusion repeated every 3 weeks. The study excluded patients with any evidence of cardiac disease and those who had received more than 300 mg/m² of doxorubicin during adjuvant therapy.

Less Toxicity

All patients received multiple gated acquisition (MUGA) scans at baseline and during follow-up. Treatment was discontinued if a patient had a 20% absolute decline in left ventricular ejection fraction, a 10% decline that dropped the ejection fraction below 50%, or clinically evident congestive heart failure (CHF).

In general, the liposomal formulation was associated with less severe toxicity. “The most striking finding of the study has been the cardioprotective effect of Evacet,” he said. “We saw a very low rate of cardiotoxicity with the liposomal formulation, whereas we saw problems fairly frequently with free doxorubicin, beginning at a cumulative dose of 400 mg/m².”

Aside from the overall difference in cardiac dysfunction (27% vs 13%), patients in the Evacet group had a 1% incidence of CHF vs 6% in the doxorubicin group. The one patient who developed CHF with Evacet did so at a cumulative dose in excess of 1,100 mg/m². The CHF cases in the free doxorubicin group had cumulative lifetime doses of 525 to 765 mg/m².

 
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