Cardioprotective Effect of Dexrazoxane in Patients with HER2-Positive Breast Cancer Who Receive Anthracycline Based Adjuvant Chemotherapy Followed by Trastuzumab

Abstract

PurposeWe intended to determine whether dexrazoxane (DZR) is cardioprotective during administration of adjuvant anthracycline-based chemotherapy followed by a 1-year trastuzumab treatment.MethodsThe medical records of 228 patients who underwent surgical resection and received adjuvant chemotherapy with trastuzumab for human epidermal growth factor receptor type 2 (HER2)-positive breast cancer between January 2010 and December 2014 were reviewed. Approximately 25% of patients received DZR prior to each administration of doxorubicin during doxorubicin with cyclophosphamide (AC) chemotherapy. DZR was not administered during the 1-year trastuzumab maintenance period. Rates of cardiac events (reduction in left ventricular ejection fraction [LVEF] by 10% or more; reduction in absolute LVEF to <45%) and cardiac event-free duration (CFD) were examined. The trastuzumab interruption rate was also assessed.ResultsTwelve percent of patients experienced a cardiac event. Repeated-measures analysis of variance for ejection fraction revealed a significant main effect of time, and a significant group (DZR)×time interaction. The group treated with adjuvant chemotherapy and DZR experienced significantly lower frequencies of cardiac events than the adjuvant chemotherapy only group. In multivariate analysis, DZR administration was associated with significantly fewer cardiac events. Moreover, DZR administration was an independent good prognostic factor for CFD. Only one patient (2.3%) experienced early interruption of trastuzumab in the adjuvant chemotherapy with DZR group due to cardiac toxicity, whereas 10 patients (7.6%) experienced a trastuzumab stop event in the adjuvant chemotherapy only group.ConclusionDZR is cardioprotective in HER2-positive breast cancer patients who received adjuvant chemotherapy with trastuzumab. A large cohort randomized trial is needed to determine if DZR has an effect on trastuzumab interruption and completion of 12-month trastuzumab. Because cardiac toxicity has a significant negative effect on trastuzumab maintenance and quality of life, DZR administration could be considered concomitantly with anthracycline-based adjuvant chemotherapy with trastuzumab.

Effects of dexrazoxane on doxorubicin-related cardiotoxicity and second malignant neoplasms in children with osteosarcoma: a report from the Children’s Oncology Group

“…Trastuzumab alone had a relative risk of 5.11 for severe heart failure in a meta-analysis of women with breast cancer [35]. A retrospective study of women with HER2positive breast cancer who received doxorubicin and trastuzumab showed that the 25% who received dexrazoxane had significantly fewer cardiac events [36]. Our study supports this impression that dexrazoxane may mitigate the cardiotoxicity of doxorubicin given with trastuzumab.…”

A Systematic Review on Cardioprotection Strategies to Prevent Breast Cancer Therapy Cardiotoxicity

“…LVEF with echocardiography, cardiac MRI, MUGA, and echocardiography and MUGA were analyzed in 15 [9][10][11][12][13][15][16][17][18][19][20][21][22]25,26], 2 [14,23], 1 [27], and 1 [24] studies, respectively. Cardiac biomarkers, such as NT-pro-BNP, cardiac troponin, and cardiac troponin T were examined in 3 [12,16,22], 3 studies [11,14,16], and 2 [18,22] studies, respectively.…”

Inequity in Cardio‐Oncology: Identifying Disparities in Cardiotoxicity and Links to Cardiac and Cancer Outcomes

“…Only 21% of identified cohort studies and clinical trials on cardioprotective therapies provide either demographic information on the race and ethnicity of study participants or demographic information on participants’ socioeconomic status or other social determinants of health, though it does bear noting that some of the included studies were conducted in European countries with universal health care (Table S1 ). 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 In accordance with the National Institutes of Health Revitalization Act, 115 achieving diverse representation in clinical trials on cardioprotective therapies must be made a priority. Doing so will require direct targeting of known barriers to clinical trial enrollment (including patient trust, healthcare access, education, and communication) 116 as well as explorations of factors specific to cardioprotection studies.…”