MONTREALSingle-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.
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.
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.