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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sequential administration of the association of 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel could be better tolerated than the association of an anthracycline and paclitaxel while having a similar antitumour effect. 69 patients with advanced breast cancer previously untreated with anthracyclines or paclitaxel entered a phase II multicentre study in which FEC was followed by paclitaxel. Both regimens were administered 4 times every 21 days. The median follow-up is 20 months and 38/69 patients have died. Grade III-IV toxicity was acceptable. Leukopenia occurred in 26% of patients, thrombocytopenia in 2% and anaemia in 4%. One patient had reversible heart failure during FEC therapy. Peripheral neuropathy and arthralgia-myalgia occurred in 9% and 4% of patients, respectively and one patient had respiratory hypersensitivity during paclitaxel treatment. 9 patients did not complete therapy because of: treatment refusal (n = 1), cardiac toxicity (n = 1), early death during FEC chemotherapy (n = 1), major protocol violations (n = 4), hypersensitivity reaction (n = 1) and early death during paclitaxel chemotherapy (n = 1). The overall response rate was 65% (95% CI = 53-76), and 7% of patients had stable disease. Therapy was defined as having failed in 28% of patients because they were not evaluable (13%) or had progressive disease (15%). The median time to progression and survival are 13.2 and 23.5 months, respectively. Sequential FEC-paclitaxel is a suitable strategy for patients with metastatic breast cancer who have not been previously treated with anthracyclines and/or taxanes. In fact, it avoids major haematologic toxicity and has a good antitumour effect.
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PMID:A phase II study of sequential 5-fluorouracil, epirubicin and cyclophosphamide (FEC) and paclitaxel in advanced breast cancer (Protocol PV BC 97/01). 1146 Oct 67

In HER2-positive breast cancer patients, the humanized anti-HER-2 monoclonal antibody trastuzumab (Herceptin) may improve overall survival. No reports exist regarding the application of trastuzumab in patients with cytotoxically induced cardiac failure and decreased left ventricular ejection fraction or about locally recurrent and advanced disease. In this case report, trastuzumab resulted in a complete and long-lasting response of recurrent and locally advanced breast cancer and was well tolerated in a severely cytotoxically pretreated patient with cardiac failure. We encourage other oncologists to offer trastuzumab also to severely cytotoxically pretreated patients with conditions after cardiac insufficiency or with locally advanced breast cancer.
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PMID:Effectiveness of Trastuzumab (Herceptin) in a patient with locally recurrent breast cancer after cardiac failure caused by severe cytotoxic pretreatment. 1172 Nov 73

In order to explore activity and pharmacokinetic data of a docetaxel-epirubicin combination we analyzed a population of 60 metastatic breast cancer patients. All the patients had an ECOG performance status < 3; 41 patients (68%) had visceral metastases as dominant site of disease, including 33% with liver metastases. Three or more involved organs were present in 43% of patients; 35% had received prior hormonotherapy; 10% for metastatic disease. Twenty-five patients (42%) had received prior adjuvant chemotherapy; 15% a CAF regimen. Twenty per cent of patients had less than 12 months disease-free interval. Docetaxel and epirubicin were both given at a dose of 75 mg/m2 i.v. d. 1 every 3 weeks. After a median of six cycles we had 5 CR (8.3%), 40 PR (66.6%), 7 NC (11.6%), and 8 PD (13.3%). Response rates in patients with visceral and liver metastases were 78% and 55% respectively. Premenopausal status, < 1 year disease free survival and > 3 metastatic sites were associated with a lower response rate. After a median follow-up of 19 months (12-36), median disease-free survival is 11 months and median overall survival has not been reached. Grade 4 neutropenia was observed in 75% of courses but with febrile neutropenia in 6.2% of courses only. Non-hematologic toxicity wasn't clinically important. A NYHA class III reversible cardiac failure was observed in one patient (1.6%). The pharmacokinetic evaluation in 16 patients has shown that docetaxel transiently interfered with epirubicin plasma level when docetaxel was administered 1 h after epirubicin.
Breast Cancer Res Treat 2001 Dec
PMID:Clinical and pharmacokinetic data of a docetaxel-epirubicin combination in metastatic breast cancer. 1180 82

This column is the third in a series reporting on Health Care Financing Administration (HCFA) initiatives to improve care for Medicare beneficiaries with heart failure. The first paper outlined the history of HCFA quality improvement projects and current initiatives to improve care in six priority areas: heart failure, acute myocardial infarction, stroke, pneumonia, diabetes, and breast cancer. The second reported in more detail the structure of the national inpatient fee-for-service heart failure initiative, known as the National Heart Failure project. It described the development of the quality indicators, the sampling strategy for selecting charts to be reviewed, and the types of local efforts spurred by the project through the activities of each state's HCFA contractor peer review organization. This article discusses baseline quality indicator rates from the National Heart Failure project. (c)2001 by CHF, Inc.
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PMID:Baseline quality indicator rates from the National Heart Failure Project: a HCFA initiative to improve the care of medicare beneficiaries with heart failure. 1182 38

The present trial was designed to determine the efficacy of the combination of gemcitabine/doxorubicin/paclitaxel (GAT) delivered every other week as first-line therapy in patients with metastatic breast cancer. From February 1998 to September 1999, 41 patients were included in this trial. Doses delivered were doxorubicin 30 mg/m2 on day 1 and paclitaxel 135 mg/m2 plus gemcitabine 2500 mg/m2 both given on day 2, every 14 days. Doses were selected from a previous phase I trial conducted at our institution. Eligibility criteria for the phase II trial included histologically confirmed metastatic breast cancer with bidimensionally measurable lesions; no prior therapy for metastatic disease; adjuvant or neoadjuvant chemotherapy was allowed if given more than 1 year before and cumulative doses of doxorubicin or epirubicin were less than 200 mg/m2 or 360 mg/m2, respectively; Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less; and adequate hematological, hepatic, and renal function. Prophylactic use of granulocyte colony-simulating factor (G-CSF) was allowed if patients were not fully recovered (absolute neutrophil count greater than 1500/microL) from chemotherapy administration before the next dose. Left ventricular ejection fraction was determined initially, at the end of the study, and every 6 months thereafter. The patients' median age was 55 years (range, 33-68 years), and their median ECOG performance status was 0 (range, 0-1). Twenty-eight patients had received adjuvant therapy, 17 with epirubicin (none with doxorubicin). Metastases were present in the bone (19 patients), lung (19 patients), liver (11 patients), and soft tissues (18 patients). Twenty patients had one metastatic site and 21 had two or more sites. Efficacy was assessed on an intent-to-treat basis. A total of 216 cycles of GAT were given. Twenty-two percent of the courses were delayed or given at reduced doses mostly due to neutropenia or thrombocytopenia. G-CSF was required in 58% of the cycles. Grade 3/4 neutropenia was the main toxicity and appeared in 17 patients, one of whom had an episode of febrile neutropenia. Nonhematological toxicities consisted mainly of neurotoxicity and myalgias. A drop of 10%-20% in the left ventricular ejection fraction was detected in two patients and another patient had a decrease greater than 20%, although none developed symptoms of heart failure. Overall response rate was 80.4% (95% confidence interval: 68.3-92.5), with 15 patients (36.6%) achieving a complete response. Median survival time was 27 months and median time to progression was 15 months. The GAT combination is feasible and very active in patients with metastatic breast cancer, with an encouraging response rate including a high rate of complete responses. No congestive heart failure was documented and other toxicities were mild, with the exception of neutropenia.
Clin Breast Cancer 2000 Oct
PMID:Phase II trial of gemcitabine/doxorubicin/paclitaxel administered every other week in patients with metastatic breast cancer. 1189 47

Every year in the US heart failure accounts for roughly 60,000 deaths and is the contributing cause in another 300,000 deaths. The two-year survival rate for patients with advanced heart failure is less than 50%, with the incidence of death at 106 in 100,000, more than that for AIDS and breast cancer combined. As these figures attest, the economic burden is quite extensive. The Centers for Medicaid and Medicare estimate a cost of $10 billion a year for this diagnosis alone. Both the human and financial cost have impelled doctors and researchers to improve their capacity to treat heart failure both through conventional methods and, in the most serious cases, through transplantation. Many pioneers have either directly or indirectly contributed to our ability to treat heart failure. Among these early researchers were: Dr Alexis Carrel, who was awarded the Nobel Prize for his pioneering work in vascular anastomosis; Dr John Gibbon, who did important work in the development of the cardiopulmonary bypass machine; Drs Normal Shumway, Richard Lower, and Demikhov, who developed heart transplant procedures in the canine model; Dr Christian Barnaard, who performed the first technically successful human-to-human heart transplant (1967); and Dr Thomas Hardy, who attempted the first xenotransplant (1963). While these achievements were phenomenal advances, long-term survival for transplant recipients was minimal until progress was made in immunosuppressive techniques.
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PMID:Heart transplants: need versus availability. 1191 Oct 12

Amplification of the gene encoding the ErbB2 (Her2/neu) receptor tyrosine kinase is critical for the progression of several forms of breast cancer. In a large-scale clinical trial, treatment with Herceptin (trastuzumab), a humanized blocking antibody against ErbB2, led to marked improvement in survival. However, cardiomyopathy was uncovered as a mitigating side effect, thereby suggesting an important role for ErbB2 signaling as a modifier of human heart failure. To investigate the physiological role of ErbB2 signaling in the adult heart, we generated mice with a ventricular-restricted deletion of Erbb2. These ErbB2-deficient conditional mutant mice were viable and displayed no overt phenotype. However, physiological analysis revealed the onset of multiple independent parameters of dilated cardiomyopathy, including chamber dilation, wall thinning and decreased contractility. Additionally, cardiomyocytes isolated from these conditional mutants were more susceptible to anthracycline toxicity. ErbB2 signaling in cardiomyocytes is therefore essential for the prevention of dilated cardiomyopathy.
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PMID:ErbB2 is essential in the prevention of dilated cardiomyopathy. 1198 89

Trastuzumab, a monoclonal antibody that is selective for cells that overexpress the erbB2 receptor protein tyrosine kinase, is a promising targeted therapy for the treatment of breast cancer. Surprisingly, toxic cardiovascular side effects were discovered in late-phase clinical trials, and these effects were most prominent when trastuzumab was combined with anthracycline chemotherapy. We review recent data focusing on how erbB2 monoclonal antibodies could exert a cardiotoxic effect through unique cardiomyocyte cell surface and intracellular structural features, and how an individual's cardiac susceptibility to erbB2 monoclonal antibodies may be dictated by the ability of erbB2 monoclonal antibodies to bind cardiomyocytes. In addition, we discuss ways that anthracyclines may also affect erbB2/erbB4/neuregulin receptor signaling, explaining the apparent synergistic effect. Further investigation of the role of normal and aberrant erbB2 signaling in the development of cardiac dysfunction could lead to an improved understanding of the pathophysiology of cardiac dysfunction and may lead to novel therapies for the treatment of heart failure, regardless of etiology. Understanding the nature and specificity of trastuzumab's cardiotoxic effects is important in better defining clinical criteria for inclusion and exclusion of patients who can safely receive trastuzumab for the treatment of breast cancer, or possibly other malignancies.
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PMID:Trastuzumab cardiotoxicity: Speculations regarding pathophysiology and targets for further study. 1213 94

This is the second in a series describing Health Care Financing Administration (HCFA) initiatives to improve care for Medicare beneficiaries with heart failure. The first article outlined the history of HCFA quality-improvement projects and current initiatives to improve care in six priority areas: heart failure, acute myocardial infarction, stroke, pneumonia, diabetes, and breast cancer. This article details the objectives and design of the Medicare National Heart Failure Quality Improvement Project (NHF), which has as its goal the improvement of inpatient heart failure care. (c)2000 by CHF, Inc.
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PMID:The National Heart Failure Project: a health care financing administration initiative to improve the care of Medicare beneficiaries with heart failure. 1218 41

Protein arrays are now an attractive proposition as they can measure a diverse range of protein interactions not possible with traditional DNA arrays. Antibody arrays are a specific subset of this technology. Originally conceived as multi-analyte detectors, antibody arrays are now used in a wide variety of applications. For instance, the potential of this technology to diagnose human diseases, such as leukemia, breast cancer and, potentially, heart failure, has stimulated much interest. Furthermore, identification of new protein targets in particular disease states will prove to be an invaluable tool in drug discovery and development. Patient prognosis and treatment are also potential applications of the technology. Antibody arrays have proved to be dynamic in response to these broad range of possibilities. This review examines variations in antibody array design and discusses current and potential applications of this novel and interesting technology.
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PMID:Antibody arrays: an embryonic but rapidly growing technology. 1254 81


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