Independent Adjudication of Symptomatic Heart Failure With the Use of Doxorubicin and Cyclophosphamide Followed by Trastuzumab Adjuvant Therapy: A Combined Review of Cardiac Data From the National Surgical Adjuvant Breast and Bowel Project B-31 and the North Central Cancer Treatment Group N9831 Clinical Trials
ABSTRACT An independent Adjuvant Cardiac Review and Evaluation Committee (ACREC) systematically reviewed cases of symptomatic heart failure events to uniformly define the cardiac event rate across two large trials (National Surgical Adjuvant Breast and Bowel Project [NSABP] B-31 and North Central Cancer Treatment Group [NCCTG] N9831) that assessed the addition of trastuzumab to standard adjuvant chemotherapy.
The committee was composed of six independent oncologists and cardiologists. A retrospective review of patients with a cardiac event was performed by the primary investigators of the trials. The ACREC prospectively established criteria for determining a symptomatic heart failure event. Recovery status was determined from documented resolution of signs and symptoms. Potential risk factors were also assessed.
Medical records for a total of 173 patients were reviewed: 40 in the chemotherapy-alone arm and 133 in the trastuzumab arm. Trastuzumab-treated patients had a 2.0% incidence of symptomatic heart failure events compared with 0.45% in the chemotherapy-alone arm. Complete or partial recovery was observed in 86.1% of trastuzumab-treated patients with symptomatic heart failure events. Of five patients who died, only one patient had received trastuzumab. Independent predictors for cardiac events were age older than 50 years, a low ejection fraction at the start of paclitaxel treatment, and trastuzumab treatment.
The incidence of symptomatic heart failure events is 2.0% in patients treated with adjuvant trastuzumab, and the majority of these patients recover with appropriate treatment.
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ABSTRACT: To review the evidence for the use of various biomarkers in the detection of chemotherapy associated cardiac damage.Design and methodsPubmed.gov was queried using the search words chemotherapy and cardiac biomarkers with the filters of past 10 years, humans, and English language. An emphasis was placed in obtaining primary research articles looking at the utility of biomarkers for the detection of chemotherapy-mediated cardiac injury.ResultsBiomarkers may help identify patients undergoing treatment who are at high risk for cardiotoxicity and may assist in identification of a low risk cohort that does not necessitate continued intensive screening. cTn assays are the best studied biomarkers in this context and may represent a promising and potentially valuable modality for detecting cardiac toxicity in patients undergoing chemotherapy. Monitoring cTnI levels may provide information regarding the development of cardiac toxicity before left ventricular dysfunction becomes apparent on echocardiography or via clinical symptoms. A host of other biomarkers have been evaluated for their utility in the field of chemotherapy related cardiac toxicity with intermittent success; further trials are necessary to determine what role they may end up playing for prediction and prognostication in this setting.Conclusions Biomarkers represent an exciting potential complement or replacement for echocardiographic monitoring of chemotherapy related cardiac toxicity which may allow for earlier realization of the degree of cardiac damage occurring during therapy, creating the opportunity for more timely modulation of therapy.Clinical Biochemistry 11/2014; 48(4-5). DOI:10.1016/j.clinbiochem.2014.10.013 · 2.23 Impact Factor
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ABSTRACT: Cardiovascular toxicity is unfortunately a potential short- or long-term sequela of breast cancer therapy. Both conventional chemotherapeutic agents such as anthracyclines and newer targeted agents such as trastuzumab can cause varying degrees of cardiac dysfunction. Type I cardiac toxicity is dose-dependent and irreversible, whereas Type II is not dose-dependent and is generally reversible with cessation of the drug. In this review, we discuss what is currently known about the cardiovascular effects of systemic breast cancer treatments, with a focus on the putative mechanisms of toxicity, the role of biomarkers, and potential methods of preventing and minimizing cardiovascular complications.Frontiers in Oncology 12/2014; 4:346. DOI:10.3389/fonc.2014.00346
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ABSTRACT: We evaluated the tolerability and cardiac safety of docetaxel, cyclophosphamide, and trastuzumab (TCyH) for the treatment of early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer and compared to the standard trastuzumab-based chemotherapy regimens doxorubicin with cyclophosphamide followed by paclitaxel and trastuzumab (AC-TH) and docetaxel, carboplatin, and trastuzumab (TCaH). We retrospectively reviewed early-stage, resectable, HER2-positive breast cancer patients treated with trastuzumab-based chemotherapy at a single comprehensive cancer center between 2004 and 2011. Patient characteristics, comorbidities, relative dose intensity (RDI) of each regimen, tolerability, and cardiac toxicity were evaluated. One hundred seventy-seven patients were included in the study (AC-TH, n=114; TCaH, n=39; TCyH, n=24). TCyH was solely administered in the adjuvant setting, whereas two-thirds of the AC-TH and TCaH groups were administered postoperatively. Patients treated with TCyH tended to have a more significant underlying cardiac history, higher Charlson comorbidity index, and were of an earlier stage. All patients treated with TCyH received granulocyte colony stimulating factor primary prophylaxis. No febrile neutropenia or grade ≥3 hematologic toxicity was observed in the TCyH group as compared to the AC-TH and TCaH groups. There were no significant differences in the rates of early termination, hospitalization, dose reduction, or RDI between the regimens. The symptomatic congestive heart failure rate between AC-TH, TCaH, and TCyH groups was not significantly different (4.4% vs. 2.6% vs. 8.3%, respectively, p=0.57). There was also no significant difference in the rate of early trastuzumab termination between patients treated with each regimen. TCyH is well tolerated and should be investigated as an alternative adjuvant chemotherapy option for patients who are not candidates for standard trastuzumab-containing regimens. Larger clinical trials are necessary to support the wider use of TCyH as an adjuvant regimen.Journal of Breast Cancer 12/2014; 17(4):356-62. DOI:10.4048/jbc.2014.17.4.356 · 1.32 Impact Factor