Clinical Cardiac Tolerability of Trastuzumab

Perez, Edith A.; Rodeheffer, Richard J.

doi:10.1200/jco.2004.01.120

Cited by 261 publications

(162 citation statements)

References 27 publications

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“…additional medical intervention 22,23 . The mechanism of trastuzumab-induced cardiac dysfunction is not fully understood, but is distinct from that of anthracyclines, for which the cardiotoxicity correlates with total cumulative drug dose, is irreversible and is associated with changes in myocardial ultrastructure, including vacuolization and cardiomyocyte loss 24 .…”

Section: Pressure Overload Stressmentioning

confidence: 99%

Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition

2007

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Section: Pressure Overload Stressmentioning

confidence: 99%

Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition

2007

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“…This risk appears to be higher in patients receiving concurrent anthracyclines [29]. Slamon et al [12] 123 [30].…”

Section: Discussionmentioning

confidence: 99%

Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

Stickeler¹,

Klar²,

Watermann³

et al. 2009

Breast Cancer Res Treat

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The combination therapy of doxorubicin and trastuzumab has been proven to be highly effective for metastatic breast cancer (MBC) patients with Her2/neu over-expressing tumors. However, this regimen is characterized by frequent cardiac toxicity, occurring in 27% of all treated patients and aggravating when the two substances are given concurrently. Pegylated liposomal doxorubicin (PLD) as a single agent reduces significantly cardiac toxicity and maintains efficacy compared to conventional doxorubicin. This prospective open labeled, multicenter phase II study assessed the potential cardiotoxicity and efficacy of PLD and trastuzumab as first and second line combination therapy in Her2/neu over-expressing MBC patients. Patients with Her2 over-expressing, measurable MBC with a baseline left ventricular ejection fraction (LVEF) C50% were treated with PLD 40 mg/m 2 every 4 weeks for 6 up to 9 cycles and weekly trastuzumab (4 mg/kg loading dose, then 2 mg/kg). Cardiotoxicity was defined as the appearance of clinical signs or symptoms of congestive heart failure in combination with a decrease in LVEF B44% or C10 units below the normal value of 50% in the obligatory, subsequently performed transthoracic echocardiography. Due to conflicting interests, the planned accrual goal of 30 patients was not reached. Finally 16 patients were enrolled. Ten patients presented with more than one metastatic site and six of them were in second-line therapy. The median LVEF in the study cohort was 66.1 ± 8.68% at baseline, 62.7 ± 5.11% after 6 cycles of therapy, 64.4 ± 7.61% at the first follow up and did not change significantly (61.0 ± 5.56% even at the 5th followup). Six out of 12 assessable patients (50.0%) demonstrated a clinical benefit and after a median follow-up of 15.4 months a median progression free survival of 9.67 and a median overall survival of 16.23 months. Non-cardiac side effects were mild with only 3 CTC grade 3 events of 247 treatment cycles (1.2%) and no grade 4 toxicities. The combination of PLD and trastuzumab in patients with Her2/neu over-expressing metastatic breast cancer is a safe, feasible and effective therapy. However, cardiac function should be monitored at close intervals. Due to the promising clinical response rates and mild toxicity profile in this prognostically unfavorable group, this combination therapy should be evaluated in larger studies.

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“…Other factors such as prior radiotherapy, and mean cumulative dose of doxorubicin were not found to be independent predictive factors of cardiac dysfunction (Seidman et al, 2002). Moreover, Perez and Rodeheffer (2004) reviewed data from new prospective clinical trials reporting lower incidence of trastuzumab-related cardiac toxicity when more stringent patient selection and cardiac monitoring criteria were adopted. More recently, Tan Toxicity of trastuzumab after high-dose chemotherapy C Bengala et al cardiac dysfunction associated to herceptin in combination with paclitaxel following AC regimen in high-risk breast cancer.…”

Section: Discussionmentioning

confidence: 99%

“…A part from its possible prognostic and predictive role, the HER-2 status determines the choice of treatment: when trastuzumab, a humanised monoclonal antibody that selectively binds to the extracellular domain of the HER-2 protein, is used in combination with chemotherapy, response rate, time to progression and median overall survival are improved (Slamon et al, 2001;Marty et al, 2005). Unfortunately, Trastuzumab was unexpectedly found to be associated with an increased risk of cardiac dysfunctions and asymptomatic decrease in left ventricular ejection fraction (LVEF); this risk was especially high in patient receiving concurrent anthracyclines, older than 50 years or with decreased LVEF after anthracyclines (Seidman et al, 2002;Perez and Rodeheffer, 2004;Tan-Chiu et al, 2005).…”

mentioning

confidence: 99%

Cardiac toxicity of trastuzumab in metastatic breast cancer patients previously treated with high-dose chemotherapy: a retrospective study

et al. 2006

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HER-2 overexpression is associated to a poor prognosis in high-risk and metastatic breast cancer (MBC) patients treated with highdose chemotherapy (HDC). HER-2 status is also a predictive factor and when trastuzumab is administered in combination with or sequentially to chemotherapy, a significant disease-free and/or overall survival improvement has been observed in HER-2 þ early and MBC. Unfortunately, in both settings, trastuzumab is associated with an increased risk of cardiac dysfunction (CD). We have reviewed the clinical charts of HER-2-overexpressing MBC patients treated with trastuzumab after HDC. Age, baseline left ventricular ejection fraction (LVEF), radiation therapy on cardiac area, exposure to anthracycline, single or multiple transplant, high-dose agents, trastuzumab treatment duration were recorded as potential risk factors. In total, 53 patients have been included in the analysis. Median LVEF at baseline was 60.5%; at the end of trastuzumab (data available for 28 patients only), it was 55% (P ¼ 0.01). Five out of the 28 (17.9%) patients experienced CD. Two out of 53 (3.8%) patients developed a congestive heart failure. Age X50 years and multiple transplant procedure were potential risk factors for CD. The overall incidence of CD observed in this population of HER-2 þ MBC patients treated with trastuzumab after HDC is not superior to that reported with concomitant trastuzumab and anthracyclines. However, patients with age X50 years or receiving multiple course of HDC should be considered at risk for CD.

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Clinical Cardiac Tolerability of Trastuzumab

Cited by 261 publications

References 27 publications

Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition

Molecular mechanisms of cardiotoxicity of tyrosine kinase inhibition

Pegylated liposomal doxorubicin and trastuzumab as 1st and 2nd line therapy in her2/neu positive metastatic breast cancer: a multicenter phase II trial

Cardiac toxicity of trastuzumab in metastatic breast cancer patients previously treated with high-dose chemotherapy: a retrospective study

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