Dexrazoxane is indicated as a
cardioprotective agent for patients receiving
doxorubicin who are at increased risk for
cardiotoxicity. Concerns have been raised on the use of
dexrazoxane, particularly in adjuvant
therapy, because of the risk of interference with the antitumor effect of
doxorubicin. Two meta-analyses in metastatic
breast cancer have rejected this hypothesis, but have shown an apparent increase in the severity of myelosuppression when
dexrazoxane is used. Here, we analyzed retrospectively a cohort of our institute database to assess whether the addition of
dexrazoxane causes more bone marrow suppression in
breast cancer patients receiving
doxorubicin-based adjuvant
therapy. The secondary objectives were assessment of the incidence of
febrile neutropenia, dose-schedule modifications, recorded
cardiac events or cardiac test abnormalities, and overall survival. Eight hundred and twenty-two female patients who received adjuvant (or neoadjuvant)
doxorubicin and
cyclophosphamide for
breast cancer between 2001 and 2013 were included. One hundred and four of these patients also received
dexrazoxane concurrently with the adjuvant treatment. Hospital records and, when accessible, community clinic records were reviewed. The median follow-up duration was 7 years for patients receiving
dexrazoxane and 7.5 years for patients not receiving
dexrazoxane. 85.6% of patients were alive at data lock. Compared with the nondexrazoxane group, patients who received
dexrazoxane were older (median age at diagnosis 59 vs. 52 years) and more likely to receive dose-dense AC
therapy (73 vs. 59%) and adjuvant
trastuzumab treatment (29 vs. 15%). Compared with the nondexrazoxane group,
dexrazoxane treatment was associated with a higher rate of hematological side effects:
leukopenia (48 vs. 39%),
neutropenia (45 vs. 31%, P=0.003),
anemia (86 vs. 73%, P=0.005), and
thrombocytopenia (37 vs. 22%, P=0.001). There were more
febrile neutropenia hospitalizations (20 vs. 10%, P=0.001) and
dose reductions (22 vs. 8%, P<0.001) in the
dexrazoxane group, but no significant difference in the incidence of
treatment delays or cancellations. The incidence of
cardiac events was the same in both treatment groups with and without
dexrazoxane. There was a nonsignificantly lower mortality rate in the
dexrazoxane group (9.6%) compared with the nondexrazoxane group (15.0%) at data lock. Adding
dexrazoxane to
doxorubicin in adjuvant
therapy patients leads to higher rates of bone marrow suppression in all blood components, as well as more
febrile neutropenia events, and
dose reductions. No differences in events defined as
cardiac toxicities were detected.
Dexrazoxane had no detrimental effect on survival, despite the higher hematological toxicity, the older median age, and the higher prevalence of HER2-positive disease in the
dexrazoxane group.