Longer-term cardiac safety and outcomes of dose dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) with and without lapatinib (L) in patients (pts) with early breast cancer (BC).

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 167-167
Author(s):  
Neil M. Iyengar ◽  
Patrick Glyn Morris ◽  
Sujata Patil ◽  
Carol Chen ◽  
Alyson Abbruzzi ◽  
...  
Keyword(s):  
Early Stage ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Phase Ii Studies ◽  
Increased Risk ◽  
Dose Dense

167 Background: The addition of H to chemotherapy has improved outcomes in HER2-positive early BC. This approach is associated with (w/) an increased risk (<4%) of congestive heart failure (CHF). Dose-dense (every 2 weeks) anthracycline-taxane therapy (Rx) improves survival compared to the every 3 week schedule and can be combined w/ anti-HER2 Rx w/ no increased risk of cardiotoxicity up to 36 months. Here we report the incidence of NYHA Class III/IV CHF in 2 phase II studies with longer follow-up. Methods: We conducted a retrospective review of pts w/ HER2 + early stage BC treated at MSKCC and DFCI on two trials: In trial A - pts received dd AC (60/600 mg/m2) x 4 → T (175mg/m2) x 4 (w/ pegfilgrastim) w/ H x 1 year. Trial B differed w/ use of weekly T (80mg/m2) x 12 and the addition of L (1000mg orally daily) x 1 year. Left ventricular ejection fraction (LVEF) was prospectively assessed by a multi-gated acquisition scan serially throughout Rx. Results: Trial A enrolled 70 pts and Trial B enrolled 95 pts w/ the median age of 46 years (range 27-73 years). Overall, the 5-year distant disease-free survival (DDFS) for trials A and B is 92% (95%Cl; 83-97%) and 89% (95%CI; 81-94%), respectively. The baseline median LVEF was 68% (range 52-81%). In total, 28 of 165 (17%) pts had pre-existing hypertension. Now at a median follow-up of 84 and 57 months respectively, only one (1.4%, 95%CI; 1.36-7.7%) and 4 (4.2%, 95%CI; 4.2-10.4%) pts developed CHF. Since our earlier report, 1 additional CHF event occurred (Trial B) at month 44. Conclusions: Longer follow-up of these 2 studies demonstrate that dd AC → TH with or without L is associated w/ a low risk of CHF. This is consistent w/ the long-term cardiac toxicity reported from the randomized phase III studies of H w/ conventionally scheduled anthracycline-based regimens (with or without taxanes). DDFS outcomes are also encouraging. Clinical trial information: NCT00591851 and NCT00482391.

Longer-term cardiac safety and outcomes of dose dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) and trastuzumab (H) with and without lapatinib (L) in patients (pts) with early breast cancer (BC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 630-630
Author(s):  
Patrick Glyn Morris ◽  
Neil M. Iyengar ◽  
Sujata Patil ◽  
Carol Chen ◽  
Alyson Abbruzzi ◽  
...  
Keyword(s):  
Early Stage ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Phase Ii Studies ◽  
Increased Risk ◽  
Dose Dense

630 Background: The addition of H to chemotherapy has improved outcomes in HER2-positive early BC. This approach is associated with (w/) an increased risk (<4%) of congestive heart failure (CHF). At a median f/u of 36 months, the addition of anti-HER2 Rx to dose-dense (every 2 weeks) anthracycline-taxane therapy (Rx) was not associated with excess cardiotoxicity. Here we report the incidence of NYHA Class III/IV CHF in 2 phase II studies with longer follow-up. Methods: We conducted a retrospective review of pts w/ HER2 + early stage BC treated at MSKCC and DF/HCC on two trials: In trial A - pts received dd AC (60/600 mg/m2) x 4 → T (175mg/m2) x 4 (w/ pegfilgrastim) w/ H x 1 year. Trial B differed w/ use of weekly T (80mg/m2) x 12 and the addition of L (1000mg orally daily) x 1 year. In both trials, H was begun after completion of AC and concurrent with T. Left ventricular ejection fraction (LVEF) was prospectively assessed by multi-gated acquisition scan serially throughout Rx. Results: Trial A enrolled 70 pts and Trial B enrolled 95 pts w/ the median age of 46 years (range 27-73 years). Overall, the 5-year distant disease-free survival (DDFS) for trials A and B is 92% (95%Cl; 83-97%) and 89% (95%CI; 81-94%), respectively. The baseline median LVEF was 68% (range 52-81%). In total, 28 of 165 (17%) pts had pre-existing hypertension. Now at a median follow-up of 84 and 57 months respectively, only one (1.4%, 95%CI; 1.36-7.7%) and 4 (4.2%, 95%CI; 4.2-10.4%) pts developed CHF. Since our earlier report, 1 additional CHF event occurred (Trial B) at month 44. Conclusions: Longer follow-up of these 2 studies demonstrate that dd AC → TH with or without L is associated w/ a low risk of CHF. This is consistent w/ the long-term cardiac toxicity reported from the randomized phase III studies of H w/ conventionally scheduled anthracycline-based regimens (with or without taxanes). DDFS outcomes are also encouraging. Clinical trial information: NCT00482391.

NT-ProBNP and hsTnI: A Multistate Survival Analysis in Outpatients with Reduced Left-Ventricular Ejection Fraction

Cardiology ◽  
2019 ◽  
Vol 142 (1) ◽  
pp. 7-13
Author(s):  
Gabriele Di Gesaro ◽  
Giuseppa Caccamo ◽  
Diego Bellavia ◽  
Calogero Falletta ◽  
Chiara Minà ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Troponin I ◽  
Serum Levels ◽  
Left Ventricular ◽  
Clinical Event ◽  
Left Ventricular Ejection ◽  
Baseline Serum ◽  
Ventricular Ejection Fraction ◽  
Increased Risk

Heart failure (HF) with reduced ejection fraction (HFrEF) has a well-known epidemic relevance in western countries. It affects up to 1–2% of patients > 60 years and reaches a prevalence of 12% in octogenarian patients. The role of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitive troponin I (hsTnI) in risk stratifying HFrEF patients has been established; at present, evidence is exclusively based on one-time assessments, and the prognostic usefulness of serial biochemical assessments in this population still remains to be determined. We prospectively recruited 226 patients with chronic HFrEF, who were all referred to the Outpatient Clinic of our institution from November 2011 through September 2014. Recruited patients underwent full clinical evaluation with complete history taking and physical examination as well as ECG, biochemical assessment, and standard 2D and Doppler flow echocardiography at the first visit, and then again at each visit during the follow-up, repeated every 6 months. During the follow-up period, cardiovascular (CV) death, which occurred in 16 patients, was not statistically correlated with gender (p = 0.088) or age (p = 0.1636); however, baseline serum levels of NT-proBNP, which were 3 times higher in deceased patients, were significantly related to this clinical event (p = 0.001). We found that NT-proBNP represents a strong and independent predictor of CV outcome; serum levels of hsTnI, which are significantly related to an increased risk of hospitalization, cannot properly predict the relative risk of CV mortality. Our study validates, eventually, the multimarker strategy, which reflects the complexity of the HF pathophysiology.

Neoadjuvant chemotherapy (NACT) with prolonged high-dose (HD) doxorubicin (A) and cyclophosphamide (C) with G-CSF support in locally advanced breast cancer (LABC): Long-term follow-up data

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11090-11090
Author(s):  
S. Altintas ◽  
M. T. Huizing ◽  
I. Spoormans ◽  
J. Van den Brande ◽  
P. Wilmes ◽  
...  
Keyword(s):  
Residual Disease ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
High Dose ◽  
Axillary Lymph ◽  
Study Objective ◽  
Ventricular Ejection Fraction

11090 Background: NACT improves survival in LABC. The optimal regimen, dose and duration is still under study Objective: To determine the efficacy and safety of prolonged preoperative HD-AC plus G-CSF. Methods: LABC patients (pts) were treated with AC for 6 cycles (Cy): Cy 1: A 90 mg/m2, C 1000 mg/m2; Cy 2–3: A 82.5 mg/m2, C 875 mg/m2; Cy 4–6: A 75mg/m2, C 750 mg/m2) with prophylactic (peg)filgastrim q3wks. In case of cardiotoxicity or poor tumor response (TR) pts switched to Docetaxel (D) 100mg/m2 q3wks. Within 5 weeks after NACT, pts underwent mastectomy with axillary lymph node dissection followed by radiotherapy. In case of positive estrogen (ER) or progesteron receptor (PgR), hormonal treatment was given for 5 yrs. Toxicity was scored weekly (NCI-CTC 2), response every 3 wks (WHO). Kaplan-Meier analysis was performed to calculate disease free survival (DFS) and overall survival (OS). Results: Between 8/1997 and 10/2003 21 pts (median age 55 years, range 22–74) were enrolled. One pt had stage IIB, 6 stage IIIA, 14 stage IIIB disease (10 T4d). 10 tumors were ER+, 5 PgR+, none overexpressed Her-2/Neu. A total of 130 NACT Cy was given. 15 pts completed all 6 AC Cy, 6 switched to D because of a decrease in left ventricular ejection fraction (LVEF? >10%, n=2) or insufficient TR (n=4). Dose reduction of AC was needed in 1 pt (last Cy), dose delays in 4 pts. Nausea and vomiting were generally mild; grade 4 anorexia occured in one pt. Grade 4 leucopenia and neutropenia in 14 and 18 pts, respectively. Neutropenic fever requiring hospitalization occurred in 5 pts, thrombocytopenia grade 4 in 7 pts and grade 3 anemia in 3 pts. Two pts developed cardiomyopathy (9.5%) < 2 years after NACT. The overall TR rate (PR and CR) was 81%, clinical CR rate 14%, pathologic CR rate 10% and 14% had minimal residual disease. Three pts showed SD and only 1 pt had PD. The median follow up of all pts was 51 months (range 9–110), 5 yrs DFS 47%, OS 56%. 5 yrs DFS and OS for pT4d pts was 50% and 56%, respectively. Conclusions: NACT with HD-AC plus G-CSF for 6 Cy in this poor risk population is active and further supports the use of prolonged preoperative CT. The routine use of D after a restricted number of AC Cy may further improve results and decrease (cardio)toxicity. No significant financial relationships to disclose.

Trastuzumab-Associated Cardiac Events at 8 Years of Median Follow-Up in the Herceptin Adjuvant Trial (BIG 1-01)

2014 ◽  
Vol 32 (20) ◽  
pp. 2159-2165 ◽  
Author(s):  
Evandro de Azambuja ◽  
Marion J. Procter ◽  
Dirk J. van Veldhuisen ◽  
Dominique Agbor-Tarh ◽  
Otto Metzger-Filho ◽  
...  
Keyword(s):  
Early Stage ◽  
Growth Factor Receptor ◽  
Severe Congestive Heart Failure ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Cardiac Events ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Low Incidence

Purpose To document the rate and outcome of trastuzumab-associated cardiac dysfunction in patients following 1 or 2 years of adjuvant therapy. Patients and Methods The Herceptin Adjuvant (HERA) trial is a three-arm, randomized trial comparing 2 years or 1 year of trastuzumab with observation in 5,102 patients with human epidermal growth factor receptor 2 (HER2) –positive early-stage breast cancer. Cardiac function was closely monitored. Eligible patients had left ventricular ejection fraction (LVEF) ≥ 55% at study entry following neoadjuvant chemotherapy with or without radiotherapy. This 8-year median follow-up analysis considered patients randomly assigned to 2 years or 1 year of trastuzumab or observation. Results The as-treated safety population for 2 years of trastuzumab (n = 1,673), 1 year of trastuzumab (n = 1,682), and observation (n = 1,744) is reported. Cardiac adverse events leading to discontinuation of trastuzumab occurred in 9.4% of patients in the 2-year arm and 5.2% of patients in the 1-year arm. Cardiac death, severe congestive heart failure (CHF), and confirmed significant LVEF decrease remained low in all three arms. The incidence of severe CHF (0.8%, 0.8%, and 0.0%, respectively) and confirmed significant LVEF decrease (7.2%, 4.1%, and 0.9%, respectively) was significantly higher in the 2-year and 1-year trastuzumab arms compared with the observation arm. Severe CHF was the same for 2-year and 1-year trastuzumab. Of patients with confirmed LVEF decrease receiving 2-year trastuzumab, 87.5% reached acute recovery. Of patients with confirmed LVEF decrease receiving 1-year trastuzumab, 81.2% reached acute recovery. Conclusion Long-term assessment at 8-year median follow-up confirms the low incidence of cardiac events for trastuzumab given sequentially after chemotherapy and radiotherapy, and cardiac events were reversible in the vast majority of patients.

Fluorouracil, Epirubicin, and Cyclophosphamide With Either Docetaxel or Vinorelbine, With or Without Trastuzumab, As Adjuvant Treatments of Breast Cancer: Final Results of the FinHer Trial

2009 ◽  
Vol 27 (34) ◽  
pp. 5685-5692 ◽  
Author(s):  
Heikki Joensuu ◽  
Petri Bono ◽  
Vesa Kataja ◽  
Tuomo Alanko ◽  
Riitta Kokko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Treatment ◽  
Disease Free Survival ◽  
Left Ventricular ◽  
Axillary Node ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Adjuvant Trastuzumab ◽  
Ventricular Ejection Fraction

Purpose Docetaxel has not been compared with vinorelbine as adjuvant treatment of early breast cancer. Efficacy and long-term safety of a short course of adjuvant trastuzumab administered concomitantly with chemotherapy for human epidermal growth factor receptor 2 (HER2) –positive cancer are unknown. Patients and Methods One thousand ten women with axillary node–positive or high-risk node-negative breast cancer were randomly assigned to receive three cycles of docetaxel or vinorelbine, followed in both groups by three cycles of fluorouracil, epirubicin, and cyclophosphamide (FEC). Women with HER2-positive cancer (n = 232) were further assigned to either receive or not receive trastuzumab for 9 weeks with docetaxel or vinorelbine. The median follow-up time was 62 months after random assignment. Results Women assigned to docetaxel had better distant disease–free survival (DDFS) than those assigned to vinorelbine (hazard ratio [HR] = 0.66; 95% CI, 0.49 to 0.91; P = .010). In the subgroup of HER2-positive disease, patients treated with trastuzumab tended to have better DDFS than those treated with chemotherapy only (HR = 0.65; 95% CI, 0.38 to 1.12; P = .12; with adjustment for presence of axillary nodal metastases, HR = 0.57; P = .047). In exploratory analyses, docetaxel, trastuzumab, and FEC improved DDFS compared with docetaxel plus FEC (HR = 0.32; P = .029) and vinorelbine, trastuzumab, and FEC (HR = 0.31; P = .020). The median left ventricular ejection fraction of trastuzumab-treated patients remained unaltered during the 5-year follow-up; only one woman treated with trastuzumab was diagnosed with a heart failure. Conclusion Adjuvant treatment with docetaxel improves DDFS compared with vinorelbine. A brief course of trastuzumab administered concomitantly with docetaxel is safe and effective and warrants further evaluation.

Abstract 16813: The Prevalence and Predictors of Pacing-Induced Cardiomyopathy (PICM) in Younger Patients

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Dan L Li ◽  
Zachary Yoneda ◽  
Tariq Z Issa ◽  
Jay A Montgomery ◽  
Ben B Shoemaker
Keyword(s):  
Multivariate Analysis ◽  
Left Ventricular ◽  
Interquartile Range ◽  
Older Age ◽  
Left Ventricular Ejection ◽  
Ventricular Pacing ◽  
Ventricular Ejection Fraction ◽  
Younger Patients ◽  
Increased Risk

Background: Pacing-induced cardiomyopathy (PICM) has been increasingly recognized as a cause of heart failure in patients with pacemakers. Thus far, clinical trials and observational studies of PICM have largely included elderly patients with mean age > 70 years. The prevalence and predictors of PICM in younger patients (age ≤ 59 years) after pacemaker implantation are not known. Methods: We retrospectively studied the prevalence and predictors of PICM in younger adults (18-59 years) who received single ventricular chamber or dual chamber pacemakers at Vanderbilt University Medical Center from 1986-2015. Patients without documented ventricular pacing burden, and patients with baseline left ventricular ejection fraction (LVEF) < 30% were excluded. PICM was defined as LVEF drop of ≥ 10% and LVEF < 50% during follow up in the setting of significant right ventricular pacing (≥ 20%), without alternative explanations for cardiomyopathy. Univariate and multivariable Cox proportional hazards regression models were utilized to study the factors associated with hazard of developing PICM. Results: A total of 325 patients were included in the study. 182 patients had high ventricular pacing (≥ 20%), which was associated with pre-existing atrial fibrillation (AF) and reduced baseline LVEF in addition to atrioventricular block (AVB) in the multivariate analysis. During the median follow up duration of 11.5 (Interquartile range 7 - 17) years, 38 patients (11.7%) developed PICM (1.3 per 100 patient-year). The median time to the development of PICM was 5 (Interquartile range 2 - 10) years. Older age (HR 2.5 for age ≥ 50 years, P = 0.013), reduced baseline LVEF (HR 2.4, P = 0.022), and AVB (HR 2.7, P = 0.007) were associated with an increased risk of PICM in the multivariate analysis. Furthermore, pre-existing AF was associated with an increased risk of PICM in patients without pre-implant AVB (HR 8.8 compared to the absence of both AF and AVB, P = 0.039). Conclusion: The incidence of PICM in young patients was low in this cohort of younger patients. Older age, baseline reduced LVEF, and AVB were associated with an increased risk of PICM in the young patient cohort. AF was associated with an increased risk of PICM in a subset of patients without pre-existing AVB at implant.

Abstract T P71: Risk Of Ischemic Stroke During Periods Of Warfarin Discontinuation For Surgical Procedures: A Longitudinal Study Of 4060 Patients With Atrial Fibrillation

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
M. Fareed K Suri ◽  
Nauman Jahangir ◽  
Ahmed A Malik ◽  
Mushtaq H Qureshi ◽  
Shayaan Khan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Ischemic Stroke ◽  
Surgical Procedures ◽  
Repeated Measures ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Systemic Hypertension ◽  
Ventricular Ejection Fraction ◽  
Increased Risk

BACKGROUND: The risk of ischemic stroke during periods of warfarin discontinuation for surgical procedures is recognized nut not well characterized. We performed this study to quantitate the risk of ischemic stroke associated with strial fibrillation during periods of warfarin discontinuation. METHODS: We evaluated the association of warfarin discontinuation for procedure with the incidence of ischemic stroke using pooled repeated measures and Cox proportional hazards analyses during follow-up after adjusting for age, gender, obesity, diabetes mellitus, hypercholesterolemia, cigarette smoking, and study period in a cohort of A total of 4060 patients were randomized into the AFFIRM study. Patients enrolled in the study had AF plus at least one other risk factor for stroke or death: age >65 yrs, systemic hypertension, diabetes mellitus, congestive heart failure, transient ischemic attack, prior stroke, left atrium 50+ mm, left ventricular fractional shortening <25%, or left ventricular ejection fraction <40%. RESULTS: Warfarin discontinuation for procedure occurred in 17 (0.5%) of the 11,116 person observations with a mean follow-up period of 9.9+/-1.0 years. The rate of ischemic stroke was higher among participant with warfarin discontinuation (17 of 3313 person observations versus 209 of 36505 person observations, p=0.047). Warfarin discontinuation was associated with an increased risk for ischemic stroke (relative risk [RR], 2.2; 95% CI, 0.5 to 9.3). among the 11,802 person observations after adjusting for potential confounders. CONCLUSIONS: The risk associated with discontinuation of warfarin for procedures must be recognized and considered in the risk benefit analysis of any procedure.

Trastuzumab-related subclinical cardiotoxicity in patients with early stage HER2-positive breast cancer: A retrospective single-center cohort study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 10123-10123
Author(s):  
Olexiy Aseyev ◽  
Moira Rushton-Marovac ◽  
Freya L. Crawley ◽  
Christopher Johnson ◽  
Susan Faye Dent
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Early Stage ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Her2 Positive Breast Cancer ◽  
Increased Risk ◽  
Positive Breast Cancer

10123 Background: Trastuzumab-based therapy (TT) is standard treatment for HER2-positive breast cancer (HBC). Subclinical cardiotoxicity (SCTx), defined as asymptomatic decline in left ventricular ejection fraction (LVEF) > 10% to < 50%, has been reported in up to 30 % of HBC patients (pts) receiving TT. Objectives included: determine prevalence of SCTx; associated risk factors (RF); and completion rates of TT in pts with HBC referred to a cardio-oncology clinic (COC). Methods: HBC patients receiving TT referred to the Ottawa Hospital COC were included. Demographics, TNM staging, performance status, stage, cardio-vascular (CV) RF (history of heart disease, hypertension, smoking, dyslipidemia, and diabetes), cardiac medications (CM) (ACE-inhibitors, beta-blockers), baseline LVEF, previous cancer therapy, baseline anthracycline exposure, previous radiation therapy (RT) (including mediastinal RT) were collected. LVEF was evaluated by ECHO or MUGA. Rate of successful completion of TT among pts with SCTx was determined. Risk ratio (RR) and logistic regression analysis was performed. Results: 240/408 BC pts referred to the COC (2008-2016) had HBC and 163/240 (68%) were referred with SCTx while on TT. 139/163 (85 %) pts with SCTx recovered after COC assessment: 77/163 (47%) pts were prescribed CMs. A significantly higher proportion of recovery was observed in pts who did not require CM (0.92 vs 0.78, p = 0.012; RR = 0.85, 95%CI:0.74-0.91). A total of 129/163 (79%) pts who experienced SCTx finished a full course of TT. Regression analysis found baseline LVEF, diabetes, and diastolic blood pressure as significant RFs for SCTx. There were no independent predictors for recovery after asymptomatic drop in LVEF while on TT. Diabetes (OR:2.97, 95%CI:1.3-6.8) and left chest wall RT (OR:2.4, 95%CI:1.1-5.6) significantly increased risk of permanent TT interruption in pts with asymptomatic drop in LVEF. Conclusions: The majority of HBC pts who experience SCTx can safely complete a full course of TT; many without use of CMs. While CV RFs were associated with increased risk of SCTx, this did not impact CV recovery after asymptomatic drops in LVEF.

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