Pegylated liposomal doxorubicin in combination with gemcitabine in elderly women with locally advanced or metastatic breast cancer: Safety and activity results of our clinical experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e12005-e12005
Author(s):  
B. Adamo ◽  
T. Franchina ◽  
N. Denaro ◽  
C. Garipoli ◽  
G. Ferraro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Clinical Benefit ◽  
Liposomal Doxorubicin ◽  
Elderly Women ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Advanced Breast ◽  
Left Ventricular Ejection ◽  
Grade 3

e12005 Background: Elderly breast cancer patients have an increased risk of toxicity from chemotherapy, especially from anthracycline-based regimens. Pegylated liposomal doxorubicin (PLD) has shown a better tolerability profile also in combination with gemcitabine (GEM), as evidenced in several phase II trials. The aim of this study is to retrospectively evaluate the safety and activity of this combination in chemo-naïve or pre-treated elderly patients with advanced breast cancer. Methods: From January 2006 to March 2008, 39 patients (pts) with age ≥ 65 received, at our institution, PLD 25 mg/m2 (day 1, q21) and GEM 800 mg/m2 (days 1 and 8, q21). Median age was 72 (range, 65–79). ECOG PS was 0/1/2 in 14/23/2 pts, respectively. 12 pts (31%) were chemo-naïve, 20 (51%) received prior adjuvant anthracycline-based regimens, and 7 (18%) received other chemotherapies. PLD-GEM combination was administered as first line in 35 pts (90%). Median left ventricular ejection fraction (LVEF) at baseline was 61% (range, 50%-75%). 28 patients (72%) had metastatic disease: 10 in liver, 6 in lung, 2 in skin, and 10 in multiple sites. Estrogen receptor was positive in 32 pts (82%); HER-2+ in 5 pts; 7 pts were triple negative. Results: A total of 206 cycles were administered with a mean number of cycles per patient of 5.2 (range, 3–12). Grade 3–4 neutropenia occurred in 4 (10%) and 3 patients (8%), respectively; grade 3 anemia in two pts (5%). Non-hematological toxicity was mild, with 5 cases (13%) of grade 3 mucositis, and 2 cases (5%) of grade 2 palmar-plantar erythrodysesthesia syndrome. No modifications in LVEF or toxic deaths were documented. We observed 1 CR (2.5%) and 11 PR (28.2%). Eighteen (44%) patients experienced SD for 16 weeks and an overall clinical benefit of 76.8%. Conclusions: The combination of PLD and GEM has a favorable tolerability and a safety profile with an evident clinical benefit and should represent an interesting treatment option in elderly women with advanced breast cancer. No significant financial relationships to disclose.

Bevacizumab and pegylated liposomal doxorubicin as first-line therapy for locally recurrent or metastatic breast cancer: A multicenter, single-arm phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1030-1030
Author(s):  
C. Rochlitz ◽  
C. Spirig ◽  
T. Ruhstaller ◽  
T. Suter ◽  
M. Bühlmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Cardiac Toxicity ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Advanced Breast ◽  
First Line ◽  
Hand Foot Syndrome ◽  
Grade 3

1030 Background: Bevacizumab in combination with taxanes has become a standard first-line treatment of advanced breast cancer in some countries, but there is no information on its use in combination with pegylated lipsomal doxorubicin in metastatic breast cancer. Therefore, we performed a multicenter, single-arm phase II trial to evaluate the toxicity and efficacy of pegylated liposomal doxorubicin (PLD) and bevacizumab (B) as first-line treatment in advanced breast cancer. Methods: PLD at a dose of 20 mg/m2 and B at 10 mg/kg were infused on days 1 and 15 of each 4-week cycle for a maximum of 6 cycles. Thereafter, B monotherapy was continued at the same dose until progression or toxicity. Primary endpoint was the occurrence of specific toxic events known to strongly interfere with quality of life, i.e., severe cardiac toxicity, any grade 4/5 toxicity, and selected grade 3 nonhematological toxicities (hand-foot-syndrome, cognitive disturbance, CNS hemorrhage, and mucositis/stomatitis). Secondary endpoints included overall response, progression free survival (PFS), time to treatment failure, and duration of response. Eligibility criteria included documentation of metastatic or inoperable breast cancer; measurable disease according to RECIST; erbB2-negativity; LVEF of ≥ 55%; WHO performance status 0 or 1. The study used a Herndon's two-stage design with 14 and 29 patients for stages 1 and 2, respectively. The promising rate of primary toxicity was <15% and the uninteresting rate >33%. The type I error probability was 5% and the power 80%. Results: The trial had to be stopped prematurely because of toxicity after the enrollment of 41 evaluable patients. Among these patients, 16 (39%) had grade 3 hand-foot syndrome, 1 grade 3 mucositis and 1 grade 4 cardiac toxicity. Thus, a total of 18/41 (44%, exact 95% c.i. 28–60%) of all patients had a primary toxicity. Best overall response rate was 23.3% (exact 95% c.i. 12–39%), median PFS was 7.5 months (95% c.i. 4.6–8.1 months). Conclusions: The combination of 2-weekly PLD and B in advanced breast cancer is surprisingly toxic and only modestly active and should not be further investigated. [Table: see text]

Pegylated Liposomal Doxorubicin and Trastuzumab in HER-2 Overexpressing Metastatic Breast Cancer: A Multicenter Phase II Trial

2006 ◽  
Vol 24 (18) ◽  
pp. 2773-2778 ◽  
Author(s):  
Stephen Chia ◽  
Mark Clemons ◽  
Lee-Ann Martin ◽  
Angela Rodgers ◽  
Karen Gelmon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Phase Ii ◽  
Liposomal Doxorubicin ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Her 2 ◽  
Grade 3

Purpose Cardiotoxicity precludes the concurrent use of doxorubicin and trastuzumab. Because pegylated liposomal doxorubicin (PLD) has equal efficacy but significantly less cardiotoxicity than conventional doxorubicin, this phase II study assessed the rate of cardiotoxicity and efficacy of first-line PLD plus trastuzumab in HER-2–positive metastatic breast cancer (MBC). Patients and Methods Women with HER-2–positive, measurable MBC, and a baseline left ventricular ejection fraction (LVEF) ≥ 55% were treated with PLD 50 mg/m2 every 4 weeks for six cycles and weekly trastuzumab (4 mg/kg loading dose then 2 mg/kg thereafter). Cardiotoxicity was defined as symptomatic congestive heart failure (CHF) with ≥ 10% decline in LVEF to below lower limits of normal, ≥ 15% decline in LVEF without symptomatic CHF, or less than 10% LVEF decline to less than 45%. Results Thirty women were enrolled, 13 had received prior adjuvant anthracyclines. A median 5.5 cycles of PLD were administered. Mean baseline LVEF was 62.8%, 59.5% after cycle four, and 58.3% after cycle six. Three patients (10%) developed protocol-defined cardiotoxicity. No patients developed symptomatic CHF. Response rate was 52%, with an additional 38% stable disease rate. At a median follow-up of 13.9 months, the median progression-free survival was 12.0 months; median overall survival has not yet been reached. The most common adverse events were grade 3 hand-foot syndrome (30%) and grade 3/4 neutropenia (27%). Conclusion The combination of PLD and trastuzumab is a well tolerated and active regimen in HER-2-positive MBC. Cardiotoxicity was observed, but limited to asymptomatic declines in LVEF. Further evaluation of this combination is warranted.

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.

Myocyte cell damage after administration of doxorubicin or mitoxantrone in breast cancer patients assessed by indium 111 antimyosin monoclonal antibody studies.

1993 ◽  
Vol 11 (7) ◽  
pp. 1264-1268 ◽  
Author(s):  
M Estorch ◽  
I Carrió ◽  
D Martínez-Duncker ◽  
L Berná ◽  
G Torres ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Cell Damage ◽  
Myocardial Cell ◽  
Left Ventricular ◽  
Advanced Breast ◽  
Left Ventricular Ejection ◽  
Antimyosin Antibody ◽  
Indium 111 ◽  
Myocardial Cell Damage

PURPOSE To compare myocyte cell damage induced by doxorubicin or mitoxantrone, we performed left ventricular ejection fraction (LVEF) measurements and indium 111 antimyosin antibody studies in a group of patients with advanced breast cancer who had been treated with these anthracycline derivatives. PATIENTS AND METHODS We studied 35 patients eligible to receive chemotherapy including the anthracyclines: doxorubicin or mitoxantrone (cumulative dose of doxorubicin, 500 mg/m2; or mitoxantrone, 120 mg/m2). LVEF was measured before and after 10 cycles of chemotherapy. Antimyosin uptake in the myocardium was quantified by means of a heart-to-lung ratio (HLR). RESULTS Patients treated with doxorubicin presented with a significant decrease in LVEF after chemotherapy (before, 60.4% +/- 8.92%; after, 49.8% +/- 9.71%; P = .001). Antimyosin uptake was observed in all patients with a HLR of 2.03 +/- 0.25. Seven of eight patients with a HLR greater than 2.03 had a greater than 10% decrease in LVEF. Patients treated with mitoxantrone did not present with a decrease in LVEF after chemotherapy (before, 55.4% +/- 6.25%; after, 55.8% +/- 7.25%; not significant). Antimyosin uptake was observed in 14 of 17 patients with a HLR of 1.77 +/- 0.18 (P < .05). CONCLUSION 111In antimyosin monoclonal antibodies defect myocardial cell damage produced by doxorubicin and mitoxantrone. In patients with advanced breast cancer, cumulative doses of 120 mg/m2 of mitoxantrone produce less myocardial cell damage than cumulative doses of 500 mg/m2 of doxorubicin. 111In antimyosin uptake without decrease in LVEF after treatment with mitoxantrone indicates the presence of myocyte cell damage, but not to the extent necessary to deteriorate function. These results indicate that 111In antimyosin antibody studies are useful in the noninvasive comparative assessment of cardiotoxicity produced by different anthracycline derivatives.

Bi-weekly liposomal doxorubicin for advanced breast cancer in elderly women (≥70years)

2013 ◽  
Vol 4 (4) ◽  
pp. 340-345 ◽  
Author(s):  
Umberto Basso ◽  
Anna Roma ◽  
Antonella Brunello ◽  
Cristina Falci ◽  
Pasquale Fiduccia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Elderly Women ◽  
Advanced Breast

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.

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