Neoadjuvant trastuzumab in locally advanced breast cancer (NOAH): Antitumour and safety analysis

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 532-532 ◽  
Author(s):  
L. Gianni ◽  
V. Semiglazov ◽  
G. M. Manikhas ◽  
W. Eiermann ◽  
A. Lluch ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Left Ventricular ◽  
Advanced Breast ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction

532 Background: NOAH (NeOAdjuvant Herceptin) is a Phase III trial of neoadjuvant trastuzumab; H) in combination with chemotherapy in patients (pts) with HER2-positive locally advanced breast cancer (LABC). Methods: 228 pts with centrally confirmed HER2-positive (IHC 3+ or FISH+) LABC received 3 cycles of doxorubicin-paclitaxel (AT: A 60 mg/m2, T 150 mg/m2 q3w), 4 cycles of T (175 mg/m2 q3w) and 3 cycles of cyclophosphamide/methotrexate/5-fluorouracil (CMF: C 600 mg/m2, M 40 mg/m2, F 600 mg/m2 q4w) on days 1 and 8, with (n=115) or without (n=113) concomitant H (8 mg/kg loading dose then 6 mg/kg q3w for 1 year) before surgery. Pts with HER2- negative disease (IHC 0/1+; n=99) were treated in parallel with AT/T/CMF. The primary end point was event-free survival (EFS); secondary end points included overall response rate (ORR), pathological complete response (pCR) rate and safety. Results: Baseline characteristics were well balanced for randomised pts. Median tumour size was 5.5 cm (range 1.5–20.0). Inflammatory breast cancer (IBC) was present in 40% of HER2-positive vs 14% of HER2-negative tumours, while 35% vs 65%, respectively, were hormone receptor positive. Left ventricular ejection fraction (LVEF) at baseline was similar in all 3 groups. Adding H to AT/T/CMF improved ORR (81% vs 73%; p=0.18) and significantly increased pCR rate (43% vs 23%; p=0.002). This response pattern was also seen in IBC pts. ORR (66%) and pCR rate (17%) for pts with HER2-negative disease were similar to pt responses in the HER2-positive group who did not receive H. The most common serious adverse event was febrile neutropenia (8% with H vs 4% without). Only 11% of pts receiving H had absolute LVEF decreases of =10% and 1 pt treated with H experienced a cardiac event with an LVEF value of <45%. One pt with HER2-negative disease died after surgery due to pulmonary embolism. Conclusions: Neoadjuvant H plus AT/CMF-containing chemotherapy significantly improved the pCR rate of LABC vs chemotherapy alone. Treatment was well tolerated with acceptable cardiac safety. Follow-up is ongoing and EFS is maturing. [Table: see text]

scholarly journals CORRELATION BETWEEN CHANGES OF NT-PRO BNP AND HS-TROPONIN I LEVEL WITH CARDIOTOXICITY IN LOCALLY ADVANCED BREAST CANCER AFTER THREE CYCLES OF NEOADJUVANT CAF CHEMOTHERAPY

2019 ◽  
Vol 26 (1) ◽  
pp. 71
Author(s):  
Cicilia Indriaty ◽  
Leonita Anniwati ◽  
J.Nugroho Eko Putranto ◽  
Desak Gede Agung Suprabawati
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Troponin I ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Left Ventricular ◽  
Advanced Breast ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Before And After

Chemotherapy with cyclophosphamide, adriamycin, and fluorouracil (CAF) regiment in patients with locally advanced breast cancer have a risk of cardiotoxicity. Cardiotoxicity examination standards using left ventricular ejection fraction (LVEF) by echocardiography are considered insensitive for detection of subclinical ventricular dysfunction. NT-pro BNP and Hs-Troponin I (hs-TnI) as cardiac biomarkers are expected to help detect early cardiotoxicity. This study intended to analyze the correlation between changes of NT-pro BNP and hs-TnI levels with cardiotoxicity in breast cancer after three cycles of chemotherapy.This was a cross-sectional observational study, conducted at the Dr. Soetomo General Hospital Surabaya. The subjects consisted of 23 breast cancer patients who underwent chemotherapy with CAF regiment. NT-proBNP and hs-TnI examination used CLIA methods (Immulite 1000, ADVIA Centaur TnI-Ultra). Cardiotoxicity based on decreased  LVEF to more than 10% of the initial LVEF value using echocardiography. Significant increases in NT pro BNP and hs-TnI levels were obtained before and after treatment (p=0.000, p=0.002). A significant decrease in LVEF was obtained before and after treatment (p=0.000), but only 2 patients (8.7%) showed cardiotoxicity. There was no correlation between changes in NT-pro BNP and hs-TnI levels with changes in LVEF before and after chemotherapy (p=0.666 and r=0.095; p=0.254 and r=-0.28). There was no correlation between changes in NT-pro BNP and hs-TnI levels with cardiotoxicity, which was assessed based on LVEF reduction, in locally advanced breast cancer after three-cycles of chemotherapy with CAF regiment.

A randomized comparison of single-agent doxorubicin and epirubicin as first-line cytotoxic therapy in advanced breast cancer.

1991 ◽  
Vol 9 (12) ◽  
pp. 2148-2152 ◽  
Author(s):  
D J Perez ◽  
V J Harvey ◽  
B A Robinson ◽  
C H Atkinson ◽  
P J Dady ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Advanced Breast Cancer ◽  
Cardiac Failure ◽  
Response Duration ◽  
Left Ventricular ◽  
Advanced Breast ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction

One hundred forty-one patients with advanced breast cancer who had not received prior chemotherapy were randomly assigned to receive doxorubicin 60 mg/m2 or epirubicin 90 mg/m2 every 3 weeks. These doses were selected to produce equivalent toxicities. All patients were assessed for toxicity, and 138 patients were assessable for response. After a median of five treatment cycles, 47% (32 of 68) of doxorubicin-treated patients achieved a partial or complete response. Response duration and survival were 10 and 12 months for doxorubicin and 8 and 10 months for epirubicin, respectively. Noncardiac toxicities were similar for both drugs. Of 41 patients receiving doxorubicin who had serial left ventricular ejection fraction assessments, seven sustained a fall of 10% or more, and one patient developed congestive cardiac failure at a cumulative doxorubicin dose of 489 mg/m2. Of 39 patients receiving epirubicin who had serial cardiac assessments, five sustained left ventricular ejection fraction falls of 10% or more and two patients developed congestive cardiac failure at cumulative doses of 178 mg/m2 and 833 mg/m2. These data indicate that an epirubicin dose of 90 mg/m2 produces toxicity equivalent to doxorubicin 60 mg/m2 but does not improve response rates, response duration, or survival in advanced breast cancer.

Safety analysis from PACS 04—A phase III trial comparing 6 cycles of FEC100 with 6 cycles of ET75 for node-positive early breast cancer patients, followed by sequential trastuzumab in HER2+ patients: Preliminary results

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 632-632 ◽  
Author(s):  
M. Spielmann ◽  
H. Roché ◽  
T. Delozier ◽  
G. Romieu ◽  
H. Bourgeois ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Safety Data ◽  
Left Ventricular ◽  
Phase Iii ◽  
Left Ventricular Ejection ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Ventricular Ejection Fraction ◽  
Phase Iii Trial ◽  
Post Surgery

632 Background: Following the BCIRG 001, PACS 01 and HERA trials, this randomised, multicentre, open-label, Phase III trial was designed to demonstrate the benefit of concomitant docetaxel and epirubicin versus anthracyclines, and evaluate the use of sequential trastuzumab. Methods: Patients (pts) with localised, resectable, unilateral breast cancer who met the following criteria were eligible: age <65 years, ≥1 positive node, M0, adequate heart and organ functions. Pts were randomised to receive either 6 cycles of 5-fluorouracil-epirubicin-cyclophosphamide (FEC100: F and C, 500 mg/m2, E 100 mg/m2) (Arm A) or epirubicin-docetaxel (ET75: E 75 mg/m2, T 75 mg/m2) (Arm B). Primary prophylaxis with G-CSF was not planned. Radiotherapy was mandatory after conservative surgery and tamoxifen was required in pts with hormone receptor-positive tumours. Pts with HER2-positive disease were then further randomised to observation only or to 1 year of trastuzumab monotherapy (6 mg/kg iv every 3 weeks). In HER2-positive pts receiving trastuzumab, left ventricular ejection fraction (LVEF) was determined at Cycles 2, 4, 8, 13, 18 and after 2 years. Otherwise, LVEF was determined at baseline and at 1 year post-surgery. Results: Of the 3010 pts recruited (2622 evaluable for safety to date), 1518 received FEC100 and 1492 received ET75 after the first randomisation. Haematologic toxicity was the most frequent toxicity in both arms. Grade 3–4 toxicities were similar for Arms A and B, except febrile neutropenia (10.3% and 31.4%, respectively) and nausea/vomiting (13.2% and 7.5%, respectively). Grade 2 clinical cardiac toxicity (decreased LVEF) was observed in 4 pts in Arm A and 5 in Arm B, with median LVEF scores of 63% in both arms at the end of chemotherapy. HER2-positive pts (n=500) were then randomised to either receive trastuzumab (n=259) or observation only (n=241). Conclusions: These preliminary safety data indicate that FEC100 and ET75 were both well tolerated, with acceptable cardiac safety values. The trial is ongoing and further analysis regarding the use of trastuzumab in this setting will be presented. [Table: see text]

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