This study attempted to assess the incidence and outcome of anthracycline cardiotoxicity and the role of dexrazoxane as a cardioprotectant in childhood solid tumors. The dexrazoxane group included 47 patients and the control group of historical cohort included 42. Dexrazoxane was given in the 10:1 ratio to doxorubicin. Fractional shortening and systolic and diastolic left ventricular diameters were used to assess the cardiac function. The median follow-ups were 54 months in the dexrazoxane group and 86 months in the control group. The mean cumulative doses of doxorubicin were 280.8+/-83.4 mg/m2 in the dexrazoxane group and 266.1+/-75.0 mg/m2 in the control group. The dexrazoxane group experienced significantly fewer cardiac events (27.7% vs. 52.4%) and less severe congestive heart failure (6.4% vs. 14.3%) than the control group. Thirteen cardiotoxicities including one cardiac death and 2 congestive heart failures occurred in the dexrazoxane group, and 22 cardiotoxicities including 2 cardiac deaths and 4 congestive heart failures, in the control group. Five year cardiac event free survival rates were 69.2% in the dexrazoxane group and 45.8% in the control group (P=0.04). Dexrazoxane reduces the incidence and severity of early and late anthracycline cardiotoxicity in childhood solid tumors.
Adolescent ; Antibiotics, Antineoplastic/*adverse effects ; Cardiomyopathies/chemically induced/prevention & control ; Cardiovascular Agents/*therapeutic use ; Child ; Child, Preschool ; Cohort Studies ; Disease-Free Survival ; Doxorubicin/*adverse effects ; Echocardiography ; Female ; Follow-Up Studies ; Heart Failure/chemically induced/prevention & control ; Humans ; Infant ; Male ; Neoplasms/*drug therapy/mortality ; Razoxane/*therapeutic use ; Ventricular Function, Left/physiology

OBJECTIVETo evaluate the cardioprotective effects of dexrazoxane (DEX) on breast cancer patients who received anthracycline-containing chemotherapy.

METHODSA total of 122 breast cancer patients after operation were randomly divided into two groups: The experimental group of 61 cases treated with EPI plus DEX (DEX:EPI = 10:1) as adjuvant chemotherapy regimen, and the control group of 61 cases treated with EPI but without DEX. All patients received four cycles of adjuvant chemotherapy and their changes of specific cardiac functional status and hematology status before and after chemotherapy, as well as non-cardiac toxicity were observed and analyzed.

RESULTSBrain natriuretic peptide (BNP) before chemotherapy and after four cycles of chemotherapy in the control group was (106.78 ± 4.52)×10(-6) µg/ml and (187.19 ± 8.71)×10(-6) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (102.34 ± 8.76)×10(-6) µg/ml and (105.29 ± 7.21)×10(-6) µg/ml, respectively, without a significant difference (P > 0.05). Cardiac troponin T (cTnT) before chemotherapy and after four cycles of chemotherapy in the control group was (12.55 ± 2.73)×10(-3) µg/ml and ( 31.05 ± 7.10 )×10(-3) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (12.70 ± 2.15)×10(-3) µg/ml and (13.65 ± 7.82)×10(-3) µg/ml, respectively, without a significant difference (P > 0.05). The hart rate (HR) before chemotherapy and after four cycles of chemotherapy in the control group, was 75.32 ± 7.14 bpm and 89.60 ± 9.21 bpm, respectively, with a significant difference (P < 0.05). It in the experimental group was 78.60 ± 6.29 bpm and 83.10 ± 7.56 bpm, respectively, without a significant difference (P > 0.05). The left ventricular ejection fraction (LVEF) before chemotherapy and after four cycles of chemotherapy in the control group was (65.23 ± 7.82)% and (55.21 ± 7.23)%, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (64.12 ± 6.25)% and (59.6 ± 4.72)%, respectively, without a significant difference (P > 0.05). The absolute neutrophil count before chemotherapy and after four cycles of chemotherapy in the control group was (3.95 ± 1.36)×10(9)/L and (3.50 ± 1.52)×10(9)/L, respectively, without a significant difference (P > 0.05). It in the experimental group, was (4.96 ± 1.41)×10(9)/L and (3.10 ± 1.26)×10(9)/L, respectively, with a significant difference (P < 0.05). The incidence of grade I-IV bone marrow suppression in the experimental group was 21.3%, 16.4%, 24.6%, and 4.9%, respectively. It in the control group was 16.4%, 11.5%, 9.8%, and 5.5%, respectively, with a significant difference (P < 0.05).

CONCLUSIONSCardiac toxicity after anthracycline treatment in breast cancer patients may be significantly reduced by DEX, without increase of non-cardiac and and non-hematologic toxicity. DEX combined with anthracycline increases the risk of bone marrow suppression, therefore, peripheral blood picture should be monitored or routine bone marrow support may be needed.

Adolescent ; Adult ; Aged ; Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; Bone Marrow ; drug effects ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; physiopathology ; surgery ; Cardiovascular Agents ; adverse effects ; therapeutic use ; Chemotherapy, Adjuvant ; Epirubicin ; adverse effects ; therapeutic use ; Female ; Follow-Up Studies ; Heart Rate ; drug effects ; Humans ; Leukocyte Count ; Middle Aged ; Natriuretic Peptide, Brain ; metabolism ; Neutrophils ; cytology ; Razoxane ; adverse effects ; therapeutic use ; Stroke Volume ; drug effects ; Young Adult

PURPOSE: To find out the myocardial protective effect of cardioxane for the myocardial damage by doxorubicin. METHODS: Using Eighteen rabbits(2.0-3.2 kg), doxorubicin(30 mg/m2) was injected intravenously once a week in group I(12 rabbits) and cardioxane(600 mg/m2) was injected at 20-30 minutes before doxorubicin administration in group II(6 rabbits). After this, we operated on the rabbits when the total cumulative dose of doxorubicin was reached at 210, 240, 270 and 300 mg/m2 and observed the degree of myocardial damage with light and electronic microscope. RESULTS: In group I, rabbits with less than 210 mg/m2 of total cumulative dose of doxorubicin, there was no definite myocardial damage but with 240 mg/m2, focal degenerative change was observed and with 300 mg/m2, severe degenerative change was detected with light microscopic examination. With electronic microscope, rabbits with less than 180 mg/m2 of total cumulative dose of doxorubicin in group I, there was no evidence of myocardial damage. In 210 mg/m2, focal degenerative change was detected. With 240 mg/m2, degenerative change was much more advanced and with 300 mg/m2, severe degenerative change was detected. In group II, no definite myocardial damage was observed even though the total cumulative dose of doxorubicin reached 300 mg/m2, but with 360 mg/m2, there was a focal area where myocardial fibers were somewhat decreased, but it's difficult to say whether these decrement were due to adriamycin in the electronic microscopic examination. CONCLUSION: Cardioxane have a good protective effect for the doxorubicin induced cardiomyopathy and it will be used safely in pediatric cancer patients.
Cardiomyopathies ; Dexrazoxane* ; Doxorubicin* ; Humans ; Rabbits

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.
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*

PURPOSE: Dexrazoxane has been used as an effective cardioprotector against anthracycline cardiotoxicity. This study intended to analyze cardioprotective efficacy and secondary malignancy development, and elucidate risk factors for secondary malignancies in dexrazoxane-treated pediatric patients. MATERIALS AND METHODS: Data was collected from 15 hospitals in Korea. Patients who received any anthracyclines, and completed treatment without stem cell transplantation were included. For efficacy evaluation, the incidence of cardiac events and cardiac event-free survival rates were compared. Data about risk factors of secondary malignancies were collected. RESULTS: Data of total 1,453 cases were analyzed; dexrazoxane with every anthracyclines group (D group, 1,035 patients) and no dexrazoxane group (non-D group, 418 patients). Incidence of the reported cardiac events was not statistically different between two groups; however, the cardiac event-free survival rate of patients with more than 400 mg/m2 of anthracyclines was significantly higher in D group (91.2% vs. 80.1%, p=0.04). The 6-year cumulative incidence of secondary malignancy was not different between both groups after considering follow-up duration difference (non-D, 0.52%±0.37%; D, 0.60%±0.28%; p=0.55). The most influential risk factor for secondary malignancy was the duration of anthracycline administration according to multivariate analysis. CONCLUSION: Dexrazoxane had an efficacy in lowering cardiac event-free survival rates in patients with higher cumulative anthracyclines. As a result of multivariate analysis for assessing risk factors of secondary malignancy, the occurrence of secondary malignancy was not related to dexrazoxane administration.
Anthracyclines ; Cardiotoxicity ; Dexrazoxane ; Disease-Free Survival ; Follow-Up Studies ; Humans ; Incidence ; Korea ; Multivariate Analysis ; Neoplasms, Second Primary ; Risk Factors* ; Stem Cell Transplantation

In this study, it is to compare the effectiveness of prevention against and treatment of doxorubicin (DOX) induced cardiotoxicity by dexrazoxane and schisandrin B (Sch B) in rats. Sprague-Dawley (SD) rats were randomly divided into the following 6 groups: normal saline group, DOX group, DOX+DEX group, DOX+Sch B (80 mg x kg(-1)) group, DOX+Sch B (40 mg x kg(-1)) group and DOX+Sch B (20 mg x kg(-1)) group. The results showed that Sch B could combat the increase of myocardial enzymes in peripheral blood, decrease of the enzyme activity of myocardial tissue antioxidant enzymes and disorders of systolic and diastolic function of heart in rats intravenously injected with doxorubicin (15 mg x kg(-1)). Sch B was better than DEX in protecting rat against DOX-induced the symptoms. Sch B could protect rat against DOX-induced acute cardiomyopathy and has clinical potential applications.
Animals ; Antibiotics, Antineoplastic ; adverse effects ; Antioxidants ; metabolism ; Cardiomyopathies ; chemically induced ; drug therapy ; Cardiotoxicity ; drug therapy ; Cyclooctanes ; therapeutic use ; Dexrazoxane ; therapeutic use ; Doxorubicin ; adverse effects ; Heart ; physiopathology ; Lignans ; therapeutic use ; Myocardium ; enzymology ; Polycyclic Compounds ; therapeutic use ; Rats ; Rats, Sprague-Dawley