Search results for "CARDIOTOXICITY"
showing 10 items of 104 documents
Interferon-γ Induces Chronic Active Myocarditis and Cardiomyopathy in Transgenic Mice
2007
Chronic heart failure is associated with an activation of the immune system characterized among other factors by the cardiac synthesis and serum expression of proinflammatory cytokines. There is unequivocal clinical and experimental evidence that the cytokine tumor necrosis factor-alpha is involved in the development of chronic heart failure, but a putative cardiotoxic potential of the proinflammatory cytokine interferon (IFN)-gamma remains primarily unknown. To investigate this issue we analyzed the cardiac phenotype of SAP-IFN-gamma transgenic mice, which constitutively express IFN-gamma in their livers and hence exhibit high circulating serum levels of this cytokine. SAP-IFN-gamma mice s…
Delivery of epirubicin via slow infusion as a strategy to mitigate chemotherapy-induced cardiotoxicity
2017
Background Continuous infusion of doxorubicin has been a strategy to reduce cardiotoxicity. Epirubicin is another anthracycline in common clinical use. However, evidence is lacking regarding whether this strategy can reduce cardiotoxicity of epirubicin without compromising antineoplastic efficacy. Design and methods Healthy rats were randomized into groups: epirubicin (8 mg/kg) delivered intraperitoneally via micro osmotic pumps (MOP), epirubicin (8 mg/kg) by intraperitoneal (IP) bolus injection, and placebo control. Blood samples were collected for analyzing biomarkers of myocardial injury and pharmacokinetics. At chosen times, sub-groups of animals were sacrificed for histopathology. A mo…
Paradoxically, iron overload does not potentiate doxorubicin-induced cardiotoxicity in vitro in cardiomyocytes and in vivo in mice
2015
Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran-iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran-iron (15mg/kg) for 3weeks (D0-D20) and then (D21) a single su…
Gemcitabine, oxaliplatin and weekly high-dose 5-FU as 24-h infusion in chemonaive patients with advanced or metastatic pancreatic adenocarcinoma: a m…
2006
ABSTRACT Background: Combinations of gemcitabine–oxaliplatin, gemcitabine–5-fluorouracil (5-FU) and 5-FU–oxaliplatin have synergistic activity and nonoverlapping adverse effect profiles. This trial assessed efficacy and safety of the triple combination gemcitabine–oxaliplatin and infusional 5-FU in patients with locally advanced (n = 11) or metastatic (n = 32) pancreatic adenocarcinoma. Patients and methods: A total of 43 eligible patients were treated with intravenous infusions of gemcitabine (900 mg/m2 over 30 min), followed by oxaliplatin (65 mg/m2 over 2 h) and 5-FU (1500 mg/m2 over 24 h) on days 1 and 8 of a 21-day cycle. Results: Among all 43 patients, the tumor response rate was 19% …
A phase I/II trial of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab as first-line treatment in HER-2-positive locally advanced or me…
2011
Abstract Aim To assess the activity and safety of non-pegylated liposomal doxorubicin (Myocet®) in combination with docetaxel and trastuzumab as first-line treatment of patients with HER-2/neu-positive metastatic breast cancer (MBC). Patients and methods The maximum tolerated dose of the combination was defined in the phase I part of the study. In the phase II part, 45 HER-2/neu-positive MBC patients were enrolled to receive 6–8 cycles of Myocet® 50 mg/m2 (day 1), docetaxel 30 mg/m2 (days 2 and 9) plus trastuzumab (day 2, 4 mg/kg followed by 2 mg/kg/week) every 21 d until unacceptable toxicity or progression occurred. Objective response (primary end-point) and treatment tolerability were as…
The Risk of Toxicities from Trastuzumab, Alone or in Combination, in an Elderly Breast Cancer Population
2013
<b><i>Background:</i></b> Breast cancer in the elderly is associated with high recurrence and death rates, due mostly to undertreatment. Human epidermal growth factor receptor type 2 (HER2) overexpression is infrequent in older patients. Trastuzumab-based chemotherapy is often withheld from elderly patients because of its cardiotoxicity. <b><i>Patients and Methods:</i></b> Medical records of consecutive HER2-positive breast cancer patients aged ≥70 years old treated between 2005 and 2010 in the participating centers were retrospectively reviewed. All patients underwent multidimensional geriatric assessment (MGA). <b><i>Results:<…
Metformin Restores AMPK Alpha-Mediated Autophagy and Prevents Carfilzomib-Induced Cardiotoxicity In Vivo
2018
Abstract Introduction: Carfilzomib (Cfz) significantly prolongs progression-free survival in relapsed or refractory multiple myeloma patients, as highlighted in the ENDEAVOR trial. However, Cfz has high incidences of cardiotoxicity and heart failure, leading to treatment cessation. Thus, there is an imperative need for preventive therapies. The study aimed to i) establish an in vivo Cfz cardiotoxicity protocol, ii) investigate the molecular mechanism, identify molecular targets and iii) based on initial results, investigate the potential protective effect and mechanism of Metformin (Met). Methods: Male, C57BL/6 mice, were randomized in groups as following: Acute protocol (6 days): Control (…
Nine weeks versus 1 year adjuvant trastuzumab in combination with chemotherapy: final results of the phase III randomized Short-HER study
2018
Background: Chemotherapy plus 1-year trastuzumab is the standard adjuvant treatment of HER2-positive breast cancer. The efficacy of less extended trastuzumab exposure is under investigation. The short-HER study was aimed to assess the non-inferiority of 9 weeks versus 1 year of adjuvant trastuzumab combined with chemotherapy. Patients and methods: HER2-positive breast cancer patients with node-positive or, if node negative, with at least one risk factor (pT>2 cm, G3, lympho-vascular invasion, Ki-67 > 20%, age 35 years, or hormone receptor negativity) were randomly assigned to receive sequential anthracycline-taxane combinations plus 1-year trastuzumab (arm A, long) or plus 9 weeks tra…
An update on the conquests and perspectives of cardio-oncology in the field of tumor angiogenesis-targeting TKI-based therapy.
2019
Introduction: The angiogenesis mechanism is considered a crucial point in neoplastic development. A growing number of multi-targeted tyrosine kinase inhibitors (TKI) has been developed and approved for cancer treatment during the last few years. Cardiac side effects still remain an issue to manage nowadays. These drugs mechanisms and toxicities have already been discussed, hence the authors will report updates on these already available drugs. Area covered: This manuscript provides an updated review on the new mechanisms involved in angiogenesis and cardiotoxicity that are TKI-related. Here is reported an overview of the already available and the most recent TKIs under investigation in the …
Fatal heart failure induced by pazopanib in a sarcoma patient previously treated with gemcitabine
2020
Gemcitabine is commonly used for various solid organ malignancies with rarely reported cardiac side effects such as cardiomyopathy. Pazopanib usually can cause arterial hypertension but cases of heart failure have recently been re-ported. We describe a case of fatal heart failure after treatment with gemcitabine and pazopanib in a 55-year-old female with sarcoma. Patient developed left ventricular dysfunction after gemcitabine treatment and acute heart failure after 22 days of pazopanib treatment which led to death. Physicians should be aware of the cardiotoxicity risk when managing the use of pazopanib especially in patients previously treated with other cardiotoxic drugs.