J Breast Cancer.  2017 Mar;20(1):82-90. 10.4048/jbc.2017.20.1.82.

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

• Kim IH
• Lee JE
• Youn HJ
• Song BJ
• Chae BJ

• KMID: 2379402
• DOI: http://doi.org/10.4048/jbc.2017.20.1.82

Abstract

PURPOSE
We intended to determine whether dexrazoxane (DZR) is cardioprotective during administration of adjuvant anthracycline-based chemotherapy followed by a 1-year trastuzumab treatment.
METHODS
The 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.
RESULTS
Twelve 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.
CONCLUSION
DZR 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.

Keyword

Adjuvant chemotherapy; Breast neoplasms; Cardiotoxicity; Dexrazoxane; Trastuzumab

MeSH Terms

Breast Neoplasms*
Breast*
Cardiotoxicity
Chemotherapy, Adjuvant*
Cohort Studies
Cyclophosphamide
Dexrazoxane*
Doxorubicin
Drug Therapy
Humans
Medical Records
Multivariate Analysis
Quality of Life
Receptor, Epidermal Growth Factor
Stroke Volume
Trastuzumab*
Cyclophosphamide
Doxorubicin
Receptor, Epidermal Growth Factor
Trastuzumab

Figure

• 

  Figure 1 Changes in mean left ventricular ejection fraction (LVEF) depending on dexrazoxane (DZR) administration over time. Only ADJ group showed significant decrease of LVEF than ADJ with DZR group (group×time interaction, F=8.122, p<0.001). F for group, time and group×time interaction. ADJ=anthracycline-based adjuvant chemotherapy followed by trastuzumab.

• 

  Figure 2 Kaplan-Meier analysis with the log-rank test showed that ADJ with dexrazoxane (DZR) group showed remarkable prolonged cardiac event-free duration (CFD) (p=0.017) compared with only ADJ group. A cumulative 3-year cardiac event free rates were 100% and 87.1% in ADJ with DZR and only ADJ group, respectively. ADJ=anthracycline-based adjuvant chemotherapy followed by trastuzumab.

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