Dexrazoxane Adds Cardioprotective Effect in HER2-Positive Breast Cancer

Administration of dexrazoxane along with adjuvant chemotherapy was cardioprotective in patients with HER2-positive breast cancer treated with chemotherapy followed by 1 year of trastuzumab maintenance therapy, according to a new study.

“Although generally well tolerated, an important issue of concern regarding trastuzumab is cardiac toxicity, which can lead to treatment discontinuation, thus depriving patients of therapeutic benefits,” wrote study authors led by In-Ho Kim, MD, of the Catholic University of Korea College of Medicine in Seoul.

Dexrazoxane is a topoisomerase IIb inhibitor, and an intracellular iron chelator; the latter feature can reduce interactions between anthracyclines and metal ions and thus potentially reduce cardiotoxicity. The researchers reviewed records of 228 patients with HER2-positive breast cancer, and included 175 in this analysis; all underwent surgical resection and then received adjuvant chemotherapy followed by 1 year of trastuzumab maintenance therapy. The results were published online ahead of print in the Journal of Breast Cancer.

Of the full cohort, 44 patients (25.1%) received dexrazoxane prior to each administration of doxorubicin; the drug was not administered during the trastuzumab therapy period. Twenty-one patients (12%) experienced a cardiac event during the study period.

There was a significantly lower incidence of cardiac events among those treated with dexrazoxane than in those treated with adjuvant chemotherapy alone (P = .029). On a multivariate analysis, dexrazoxane administration was significantly associated with lower frequency of cardiac events, with an odds ratio of 0.01 (95% CI, 0.01–0.89; P = .039). No other clinicopathologic factors were found to have such an association.

Furthermore, administration of dexrazoxane prolonged the cardiac event-free duration compared with chemotherapy alone (P = .017). Again on a multivariate analysis, dexrazoxane administration was associated with good prognosis for cardiac event-free duration, with a hazard ratio of 0.12 (95% CI, 0.02–0.90; P = .040). Neither overall survival (P = .941) nor relapse-free survival (P = .808) were affected by dexrazoxane.

In the dexrazoxane-treated patients, only two required an interruption of trastuzumab therapy; one was due to cardiac toxicities (2.3%), and one was due to a personal reason. Among the 131 patients in the chemotherapy-alone group, 14 patients had to stop trastuzumab at some point (10.6%); this was due to cardiac toxicities in 10 patients (7.6%) and other causes in four (3.1%).

The authors noted that this was a retrospective review, with relatively small numbers of patients. Still, they wrote that the findings suggest “dexrazoxane has cardioprotective effects in HER2-positive breast cancer patients in an adjuvant setting.” Because cardiotoxicity is a significant cause of discontinuation of trastuzumab, prevention of that toxicity could carry prognostic benefits. “We therefore suggest that dexrazoxane administration could be considered during anthracycline-based adjuvant chemotherapy in HER2-positive patients who will subsequently receive a 1-year adjuvant trastuzumab treatment.”