Long term cardiac tolerability of trastuzumab in HER-2-overexpressing metastatic breast cancer (MBC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 629-629
Author(s):  
V. Guarneri ◽  
D. J. Lenihan ◽  
V. Valero ◽  
J. Durand ◽  
K. Broglio ◽  
...  
Keyword(s):  
Cardiac Toxicity ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Percentage Points ◽  
Increased Risk ◽  
One Year ◽  
Experienced Grade

629 Background: The use of trastuzumab is associated with an increased risk of cardiotoxic events such as congestive hearth failure (CHF) and decline in the left ventricular ejection fraction (LVEF). Our objectives were to evaluate the incidence of cardiac dysfunction, to identify risk factors and to evaluate the outcome of patients with MBC treated with trastuzumab for one year or longer. Methods: Among 218 MBC patients treated with trastuzumab-based therapy for at least one year, 173 patients were evaluable for cardiac toxicity. Cardiac events (CE) were defined as follows: 1) asymptomatic drop of LVEF below 50%; 2) drop of 20 percentage points in LVEF compared to the baseline; 3) signs or symptoms of CHF. The cardiac toxicity was graded according the NCI-CTCAE, version 3.0. Results: Median age at the start of trastuzumab therapy was 50 years (range, 26–79), median cumulative time on trastuzumab was 21.3 months (range, 11.6–77.6), and median follow-up was 32.2 months (range, 9.7–79.0). Eighty-five percent of patients received prior anthracyclines (median cumulative doxorubicin dose: 300 mg/m2). Forty-nine patients (28%) experienced a CE: 3 patients (1.7%) had an asymptomatic drop in the LVEF of 20 percentage points; 27 patients (15.6%) experienced grade 2 cardiac toxicity; and 18 patients (10.4%) experienced grade 3 cardiac toxicity. There was one cardiac related death (0.5%). Cardiac event-free survival was 87.3% at 1 year. All but four patients had improved LVEF or symptoms of CHF after stopping trastuzumab or with appropriate therapy. After complete recovery, 26 patients were re treated with trastuzumab; 16 patients did not experience further CE. Concomitant taxane use was the only factor significantly associated with a CE (HR: 4.37, 95%CI 1.06–17.98, p:0.04).Prior anthracycline exposure was not associated with increased risk of CE. Conclusions: The risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function. The increased risk of cardiotoxicity associated with taxane administration needs to be further investigated. No significant financial relationships to disclose.

Long-Term Cardiac Tolerability of Trastuzumab in Metastatic Breast Cancer: The M.D. Anderson Cancer Center Experience

2006 ◽  
Vol 24 (25) ◽  
pp. 4107-4115 ◽  
Author(s):  
Valentina Guarneri ◽  
Daniel J. Lenihan ◽  
Vicente Valero ◽  
Jean-Bernard Durand ◽  
Kristine Broglio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cardiac Toxicity ◽  
Metastatic Breast ◽  
Left Ventricular Ejection ◽  
Cancer Center ◽  
Percentage Points ◽  
Experienced Grade

PurposeTo evaluate the cardiac safety of long-term trastuzumab therapy in patients with human epidermal growth receptor 2 (HER2) –overexpressing metastatic breast cancer (MBC) treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX).Patients and MethodsAmong 218 MBC patients treated with trastuzumab-based therapy for at least 1 year, 173 patients were assessable for cardiac toxicity. Cardiac events (CEs) were defined as follows: asymptomatic decrease of left ventricular ejection fraction (LVEF) below 50%; decrease of 20 percentage points in LVEF compared with the baseline; or signs or symptoms of congestive heart failure (CHF).ResultsThe median cumulative time for trastuzumab administration was 21.3 months. The median follow-up was 32.6 months (range, 11.8 to 79.0 months). Forty-nine patients (28%) experienced a CE: three patients (1.7%) had an asymptomatic decrease in the LVEF of 20 percentage points, 27 patients (15.6%) experienced grade 2 cardiac toxicity, and 19 patients (10.9%) experienced grade 3 cardiac toxicity. All but three patients had improved LVEF or symptoms of CHF with trastuzumab discontinuation and appropriate therapy. There was one cardiac-related death (0.5%). Baseline LVEF was significantly associated with CE (hazard ratio, 0.94; P = .001). The hazard of a CE among patients taking concomitant taxanes was higher early in the follow-up period but declined during the course of follow-up.ConclusionThe risk of cardiac toxicity of long-term trastuzumab-based therapy is acceptable in this population, and this toxicity is reversible in the majority of the patients. In patients who have experienced a CE, additional treatment with trastuzumab can be considered after recovery of cardiac function.

Abstract 16422: Lower Mitochondrial-derived Peptide Humanin in Young Adults Born Preterm vs. Term and Association With Left Ventricular Ejection Fraction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Daniela Ravizzoni Dartora ◽  
Adrien Flahualt ◽  
Carolina Nobre Pontes ◽  
Gabriel Altit ◽  
Alyson Deprez ◽  
...  
Keyword(s):  
Young Adults ◽  
Ejection Fraction ◽  
Experimental Models ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Lv Function ◽  
Ventricular Ejection Fraction ◽  
Mitochondrial Alterations ◽  
Increased Risk

Introduction: Preterm (PT) birth is associated with increased risk of cardiovascular diseases (CVD) and heart failure. We previously reported left ventricular (LV) mitochondrial dysfunction in a rat model mimicking the deleterious conditions associated with PT birth. Whether mitochondrial function is altered in humans born PT and associated with LV function changes is unknown. We aimed to determine if serum humanin levels, a mitochondrial-derived peptide with cytoprotective effects, are altered in humans born PT and are associated with impaired myocardial function. Methods: Data were obtained from 55 young adults born PT (<30 weeks of gestational age, GA) compared to 54 full-term (T) controls of the same age. Serum humanin levels were determined by ELISA and LV ejection fraction (LVEF) by echocardiography. Results are shown as median (interquartile range) and comparisons between groups were performed using non-parametric tests. Results: Individuals were evaluated at 23.3 (21.4, 25.3) years, and age and sex distribution were similar between groups. Median GA was 27.5 (26.2, 28.4) weeks in the PT group. Humanin levels (pg/ml) were 132.9 (105.1, 189.3) and 161.1 (123.6, 252) in the PT and the T groups, respectively (p=0.0414). LVEF was within the normal range and similar between groups. Lower LVEF was associated with lower humanin levels (p<0.001), and this association was observed both in the term (p=0.002) and the preterm (p=0.047) groups. Conclusions: Serum humanin levels are lower in adult born PT. Since lower humanin levels are also associated with lower LVEF, our results suggest that mitochondrial alterations could play a role in the long-term adverse cardiovascular consequences of PT birth. Humanin analogs improve LV function in experimental models. Our results pave the way for future studies exploring humanin as a therapeutic avenue for the prevention and treatment of CVD in individuals born PT.

Phase II Trial of Liposome-Encapsulated Doxorubicin, Cyclophosphamide, and Fluorouracil as First-Line Therapy in Patients With Metastatic Breast Cancer

1999 ◽  
Vol 17 (5) ◽  
pp. 1425-1425 ◽  
Author(s):  
Vicente Valero ◽  
Aman U. Buzdar ◽  
Richard L. Theriault ◽  
Nozar Azarnia ◽  
Gustavo A. Fonseca ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Cardiac Toxicity ◽  
Metastatic Breast ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Survival Duration ◽  
First Line ◽  
Ventricular Ejection Fraction

PURPOSE: To determine the efficacy and safety profile, including the risk for cardiac toxicity, of liposome-encapsulated doxorubicin (TLC D-99), fluorouracil (5-FU), and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one women were registered in this phase II study. All patients had measurable disease and no previous chemotherapy for MBC. Treatment consisted of TLC D-99 60 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 and 5-FU 500 mg/m2 on days 1 and 8 every 3 weeks. Serial cardiac monitoring, including endomyocardial biopsies, was performed. RESULTS: The overall response rate was 73% (95% confidence interval, 57% to 86%). The median duration of response was 11.2 months, the median time to treatment failure was 8.1 months, and the median overall survival duration was 19.4 months. The median number of cycles per patient was 10. The median cumulative dose of TLC D-99 was 528 mg/m2. Ten patients required hospitalization for febrile neutropenia. Nausea/vomiting, stomatitis, and fatigue higher than grade 2 occurred in 12%, 15%, and 41% of patients, respectively. Twenty-one patients reached a cumulative doxorubicin dose greater than 500 mg/m2. Three patients (7%) were withdrawn from the study due to protocol-defined cardiac toxicity, two because of a decrease in left ventricular ejection fraction to ≤ 40%, and one because her endomyocardial biopsy result was grade 1.5. One patient had congestive heart failure that was probably nonanthracycline related. CONCLUSION: This chemotherapy regimen, including TLC D-99, was highly active against MBC and associated with low cardiac toxicity despite high cumulative doses of doxorubicin.

Phase I trial of pegylated liposomal doxorubicin and lapatinib in the treatment of metastatic breast cancer (MBC): Final results.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 610-610
Author(s):  
Mary E. Cianfrocca ◽  
Virginia G. Kaklamani ◽  
Steven T. Rosen ◽  
Jamie H. Von Roenn ◽  
Alfred Rademaker ◽  
...  
Keyword(s):  
Phase I ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Primary Objective ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Grade 3

610 Background: Liposomal formulations including pegylated liposomal doxorubicin (PLD) were developed to improve the therapeutic index of anthracyclines (A). Lapatinib (L) is a selective, highly competitive inhibitor of ErbB1 and ErbB2 tyrosine kinases. Conventional doxorubicin plus trastuzumab was effective but with unacceptable cardiac toxicity. PLD plus L may be effective with less cardiac risk. Methods: This is a phase I, dose-escalation trial of PLD 20, 30, 45 and 60 mg/m2 IV every 4 weeks (maximum of 8 doses) and L, 1500 mg po daily until progression in patients (pts) with MBC. ErbB2 positivity was not required. Prior chemotherapy, endocrine therapy and trastuzumab were allowed. A subsequent amendment allowed prior L. Prior A use was limited to 240 mg/m2 of doxorubicin or 600 mg/m2 of epirubicin. Concomitant CYP3A4 inducers/ inhibitors were not allowed. A left ventricular ejection fraction (LVEF) of > 50% was required. The primary objective was to evaluate the safety (particularly cardiac), tolerability and feasibility of PLD and L. Results: 23 pts (PLD: 20 mg/m2 - 4 pts; 30 mg/m2 - 3 pts; 45 mg/m2 – 13 pts; 60 mg/m2- 3 pts) have been treated; total of 73 treatment cycles. Dose-limiting toxicity (DLT) was not reached. One pt had an LVEF drop to < 50% after 4 cycles accompanied by a pericardial effusion due to progressive disease. Treatment-related grade III/IV adverse events included: 4 pts with hand-foot-syndrome (HFS), 2 pts each with leukopenia, infection, and skin changes, 1 pt each with pain, fatigue, diarrhea, mucositis, hypoalbuminemia, anemia, cough, pleural effusion, and edema. Grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m2 cohort. Response data in 21 evaluable pts: 4 PR, 5 SD, and 12 PD. Preliminary pharmacokinetic (PK) analyses (7 pts) indicate L has no effect on PLD (45 mg/m2) concentrations, but L concentrations were approximately 2-fold higher the day of PLD dosing. Conclusions: In 23 pts treated, PLD plus L was well tolerated with manageable toxicities and no treatment-related cardiac toxicity. DLT was not reached however grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m2 cohort. Preliminary PK analyses demonstrate no effect of L on PLD, but an effect of PLD on L the day of PLD dosing.

P969Improvement of left ventricular ejection fraction in the first week post rhythm restoration as a marker of long-term recovery of arrhythmia-induced cardiomyopathy in a latin american population

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
J L Laso Bayas ◽  
R Ibarra Castillo ◽  
J L Arbaiza Simon ◽  
M Peralta Coronel
Keyword(s):  
Left Ventricular Ejection Fraction ◽  
Latin American ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Functional Class ◽  
Rhythm Control ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
One Year

Abstract Introduction The incidence of Arrhythmia-Induced Cardiomyopathy (AIC) is presumed to be between 8% and 34%. Its outcome is also not well known and may be linked to multiple factors. However, it has been suggested that a 25% improvement of the Left Ventricular Ejection Fraction (LVEF), during the first week after rhythm restoration could be an indicator of long-term and complete recovery. This fact has not been studied in our country or even in Latin America. Purpose To observe the behavior of the LVEF after restoration of sinus rhythm in patients with systolic dysfunction presumably secondary to AIC, at least in one year of follow-up. Methods We evaluated all patients referred for arrhythmia treatment and having any degree of systolic dysfunction (LVEF less or equal to 50%) and functional class deterioration between January 2015 and September 2018. Restoration of sinus rhythm was accomplished in either by pharmacologic or invasive methods aimed to specific arrhythmias. After the treatment, we proceed with the systolic function evaluation starting one week after rhythm control, and then at one, three, six and twelve months. This evaluation consisted in clinical examination, echocardiographic determination of LVEF, as well as NT-ProBNP and troponin measurements. Results We identified twenty one cases with presumed AIC. Sixteen cases were secondary to atrial flutter, with four others being secondary to atrial fibrillation, and the last one being a consequence of frequent ventricular extrasystoles (VES). Fifteen patients (74%) were male, mean age was 51 years old (4-76 years). All cases of tachycardia had a ventricular rate over 100 beats per minute. The patient with VES, had a 58% burden of ectopic beats. Eighteen of these patients were taken to invasive electrophysiological study and radiofrequency ablation; and three patients received antiarrhythmics as rhythm control strategy. All patients had mid-range to severe systolic dysfunction prior to treatment, with a mean LVEF of 38%±7,5%; 63% of them were in NYHA class III-IV. One week after rhythm restoration, mean LVEF was 54± 6,36%. That was an improvement of 45% in LVEF. Mean LVEF at one and three months was 63± 5,43%, 61± 5,23% at six months and 63± 5,43% at one year. All patients improved their functional class, to NYHA I at the first evaluation post rhythm restoration. We found no differences between troponin and NT-ProBNP levels before and after treatment, except for one patient . Conclusion Appropriately treated AIC seems to have a good prognosis and short-term recovery of LVEF could be a useful indicator of complete normalization in the long-term. To our knowledge, here we detail the results of a relatively large time-series of AIC, and is perhaps the first study in the Latin American region that suggests that early LVEF improvement could predict AIC recovery, but controlled trials should be done in order to confirm these results.

scholarly journals Conduction System Pacing: Basis and Scope

2022 ◽  
Vol 4 (1) ◽  
pp. 01-10
Author(s):  
DR Vivek Kumar ◽  
DR Vanita Arora
Keyword(s):  
Heart Failure ◽  
Cardiovascular Death ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Heart Failure Hospitalization ◽  
Ventricular Ejection Fraction ◽  
Right Ventricular Pacing ◽  
Increased Risk ◽  
Qrs Duration

Long-term right ventricular pacing (RVP) is associated with more cardiovascular death, atrial fibrillation (AF), thromboembolic complications and heart failure(HF). RVP often results in prolonged QRS duration(QRSd) and ventricular desynchronization. The ventricular desynchronization as a result of RVP leads to an increased risk of heart failure hospitalization (HFH) and AF, and this effect is dependent on cumulative percent ventricular paced ( % VP). In the sub-study from the MOST trial, it was evident that % VP >40% was associated with a 2.6-fold increased risk of HFH compared with pacing < 40% of the time despite preserved atrioventricular synchrony. Moreover this adverse effect of RVP induced ventricular desynchrony was more pronounced in patients with left ventricular ejection fraction( LVEF) of 40% or less resulting in increased death or HFH.

scholarly journals Long-Term Cardiac Safety Analysis of NCCTG N9831 (Alliance) Adjuvant Trastuzumab Trial

2016 ◽  
Vol 34 (6) ◽  
pp. 581-587 ◽  
Author(s):  
Pooja P. Advani ◽  
Karla V. Ballman ◽  
Travis J. Dockter ◽  
Gerardo Colon-Otero ◽  
Edith A. Perez
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Cumulative Incidence ◽  
Cardiac Toxicity ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

Purpose Significant improvement in survival outcomes has been established with the addition of trastuzumab to adjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2) –positive early breast cancer treatment. However, trastuzumab may increase the risk of cardiac toxicity, and long-term evaluation of its incidence and risk factors are warranted. Methods NCCTG (Alliance) N9831 trial compared adjuvant doxorubicin and cyclophosphamide (AC) followed by either weekly paclitaxel (arm A); paclitaxel then trastuzumab (arm B); or paclitaxel plus trastuzumab followed by trastuzumab alone (arm C) in patients with HER2-positive breast cancer. Cumulative incidence of cardiac events (CE) and left ventricular ejection fraction (LVEF) were evaluated in 1,944 women who proceeded to post-AC therapy. Risk factors for trastuzumab-induced cardiac toxicity were identified by Cox regression models. Results The 6-year cumulative incidence of CE was 0.6% in arm A, 2.8% in arm B, and 3.4% in arm C. At a median follow-up of 9.2 years, only two additional CHF diagnoses (of 1,046 patients) occurred beyond our previously reported follow-up time of 3.75 years. LVEF recovered in the majority of the patients who developed CHF. There were two cardiac deaths in arm A and one each in arms B and C. Age of 60 years or older, registration LVEF less than 65%, and use of antihypertensive medications were associated with an increased risk of CE in arms B and C. Conclusion The cumulative incidence of CE at 6 years was slightly higher with the addition of trastuzumab; however, the late development of CE is infrequent. Trastuzumab (in the context of anthracycline- and taxane-based therapy) continues to have a favorable benefit-risk ratio.

scholarly journals Long-Term Efficacy and Impact on Mortality of Remote Magnetic Navigation Guided Catheter Ablation of Ventricular Arrhythmias

2021 ◽  
Vol 10 (20) ◽  
pp. 4695
Author(s):  
Denise Guckel ◽  
Sarah Niemann ◽  
Marc Ditzhaus ◽  
Stephan Molatta ◽  
Leonard Bergau ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Long Term Results ◽  
Left Ventricular Ejection ◽  
Magnetic Navigation ◽  
Premature Ventricular Contractions ◽  
Ventricular Ejection Fraction ◽  
Remote Magnetic Navigation ◽  
Term Efficacy ◽  
Increased Risk

Remote magnetic navigation (RMN) facilitates ventricular arrhythmia (VA) ablation. This study aimed to evaluate the long-term efficacy of RMN-guided ablation for ventricular tachycardia (VT) and premature ventricular contractions (PVC). A total of 176 consecutive patients (mean age 53.23 ± 17.55 years, 37% female) underwent VA ablation for PVC (132 patients, 75%) or VT (44 patients, 25%). The cohort consisted of 119 patients (68%) with idiopathic VA, 31 (18%) with ischemic (ICM), and 26 (15%) with dilated cardiomyopathy (DCM). VA recurrence was observed in 69 patients (39%, mean age 51.71 ± 19.91 years, 23% female) during a follow-up period of 5.48 years (first quartile 770.50 days, second quartile 1101.50 days, third quartile 1615.50 days). Left ventricular ejection fraction <40% lead to a significantly increased risk for VA (p = 0.031*). Multivariate analyses found DCM to be an independent predictor (IP) for VA recurrence (p < 0.001*, hazard ratio (HR) 3.74, confidence interval (CI) 1.58–8.88). ICM resulted in a lower increase in VA recurrence (p = 0.221, HR 1.49, CI 0.79–2.81). Class I/III/IV antiarrhythmic drug therapy (AADs) was also identified as IP for recurrence (p = 0.030*, HR 2.48, CI 1.11–5.68). A total of 16 patients (9%) died within the observational period. RMN-guided ablation of VA lead to acceptable long-term results. An impaired LV function, DCM, and AADs were associated with a significant risk for VA recurrence. Personalized paths are needed to improve efficacy and outcome.

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