NEW YORK--Dexrazoxane (Zine-card), which was developed in Great
Britain in the 1960s as an anticancer drug, is extremely effective
in blocking the cardiotoxic effects of doxorubicin, said James
L. Speyer, MD, professor of clinical medicine, Department of Oncology,
New York University Medical Center.
Dexrazoxane was recently approved by the FDA for use in at-risk
breast cancer patients, but may be useful for other malignancies,
including several pediatric cancers, he said in a presentation
at the Chemotherapy Foundation symposium.
Doxorubicin is a mainstay of chemotherapy in breast cancer, Hodgkin's
lymphomas, childhood leukemias, and many solid tumors, Dr. Speyer
said. Nonetheless, its tendency to induce cardiomyopathy at higher
doses poses a major clinical problem in the management of these
With higher doses and dose-intensive therapies, the problem is
becoming more common. The result is that, in an effort to avoid
toxicity, many patients do not receive optimal doses, and among
those that do, some suffer cardiac symptoms.
Children are among those whose treatments may be modified because
of cardiac risk. "Recent reports in children highlight the
increased sensitivity of this population as a function of dose,
dose intensity, age at which treatment is received, and sex,"
Dr. Speyer said.
Dexrazoxane appears to work through chelation of intracellular
iron with reduction of the iron-doxorubicin complex and decreased
free-radical production. It is not effective for preexisting cardiac
conditions, but when given in conjunction with a doxorubicin-containing
regimen, it appears to confer cardiac protection without interfering
with the antitumor action of doxorubicin. Its dose-limiting toxicity
is myelosuppres-sion, Dr. Speyer said.
Randomized trials were conducted at NYU with 150 breast cancer
patients receiving a regimen of fluorouracil, doxorubicin, and
cyclophosphamide (FAC). Seventy-six women were pretreated with
1,000 mg/m² of dexrazoxane, followed by chemotherapy; the
control group received chemotherapy alone. Study endpoints were
development of cardiotoxicity or disease progression.