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(Drug information on 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 malignancies.
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(Drug information on fluorouracil), doxorubicin, and cyclophosphamide(Drug information on 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.