pared to patients who did not. Patients unprotected by Zinecard had a 13 times greater risk of developing congestive heart failure. Overall, 3% of patients treated with Zinecard developed CHF compared with 22% of patients not receiving Zinecard.
Figure 1 Doxorubicin Dose at Congestive Heart Failure (CHF) FAC vs. FAC/Zinecard Patients Patients Receiving At Least Seven Courses of Treatment
Because of its cardioprotective effect, Zinecard permitted a greater percentage of patients to be treated with extended doxorubicin therapy. Figure 2 shows the number of patients still on treatment at increasing cumulative doses.
Figure 2 Cumulative Number of Patients On Treatment FAC vs. FAC/Zinecard Patients Patients Receiving at Least Seven Courses of Treatment
In addition to eva luating the cardioprotective efficacy of Zinecard in this setting, the time to tumor progression and survival of these two groups of patients were also compared. There was a similar time to progression in the two groups and survival was at least as long for the group of patients that received Zinecard starting with their seventh course, i.e., starting after a cumulative dose of doxorubicin of 300 mg/m2. These time to progression and survival data should be interpreted with caution, however, because they are based on comparisons of groups entered sequentially in the studies and are not comparisons of prospectively randomized patients.
Indications and Usage for Zinecard
Zinecard is indicated for reducing the incidence and severity of cardiomyopathy associated with doxorubicin administration in women with metastatic breast cancer who have received a cumulative doxorubicin dose of 300 mg/m2 and who will continue to receive doxorubicin therapy to maintain tumor control. It is not recommended for use with the initiation of doxorubicin therapy (see WARNINGS).
Contraindications
Zinecard should not be used with chemotherapy regimens that do not contain an anthracycline.
Warnings
Zinecard may add to the myelosuppression caused by chemotherapeutic agents.
There is some evidence that the use of dexrazoxane concurrently with the initiation of fluorouracil, doxorubicin, and cyclophosphamide (FAC) therapy interferes with the antitumor efficacy of the regimen, and this use is not recommended. In the largest of three breast cancer trials, patients who received dexrazoxane starting with their first cycle of FAC therapy had a lower response rate (48% vs. 63%; p=0.007) and shorter time to progression than patients who did not receive dexrazoxane (see Clinical Studies section of CLINICAL PHARMACOLOGY). Therefore, Zinecard should only be used in those patients who have received a cumulative doxorubicin dose of 300 mg/m2 and are continuing with doxorubicin therapy.
Although clinical studies have shown that patients receiving FAC with Zinecard may receive a higher cumulative dose of doxorubicin before experiencing cardiac toxicity than patients receiving FAC without Zinecard, the use of Zinecard in patients who have already received a cumulative dose of doxorubicin of 300 mg/m2 without Zinecard, does not eliminate the potential for anthracycline induced cardiac toxicity. Therefore, cardiac function should be carefully monitored.
Secondary Malignancies
Secondary malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have been reported in studies of pediatric patients who have received Zinecard in combination with chemotherapy. Zinecard i |
