Search results for "TOXICITY"

A pharmacokinetically (PK) and pharmacodynamically (PD) driven phase I trial of the pan-AKT inhibitor AZD5363 with expansion cohorts in PIK3CA mutant…

2015

Background: AZD5363 is a novel potent pan-AKT inhibitor (IC50of AKT1, AKT2 and AKT3 of 3, 7 and 7nM respectively) with preclinical activity across a range of models. Methods: The trial had an adaptive design that allowed changes in schedule based on toxicity, PK, and PD findings. AZD5363 was administered orally (PO) twice a day (BID). Three schedules were explored: continuous dosing (7/7), four days a week, (4/7) and two days a week (2/7). PD biomarkers including pAKT, pGSK3?, and pPRAS40 were measured by IHC in pre- and post-treatment tumor biopsies. Once a RP2D was established, two expansion cohorts of PIK3CA-mutant ER+ve breast (B) and gynecological (G) cancers were explored. Results: 47…

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.

Use of myocardial work for multiparametric detection of subclinical anthracycline cardiotoxicity in breast cancer patients

2021

Abstract Funding Acknowledgements Type of funding sources: None. Background The aim of our study was to assess subclinical cardiac effects of anthracyclines (ANTs) in women treated for breast cancer (BC). Methods We enrolled 46 female patients with BC undergoing adjuvant treatment with anthracycline-containing chemotherapy (CT) followed by taxane (paclitaxel/docetaxel).  Patients underwent physical examination, electrocardiogram (ECG) and standard transthoracic echocardiography (TTE) including evaluation of diastolic and systolic function, measured as left ventricular ejection fraction (LVEF), left ventricular global longitudinal strain (GLS) and myocardial work (MW) expressed as global wor…

PKP-020 Impact of nadph oxidase functional polymorphisms in acute myeloid leukaemia induction chemotherapy

2016

Background NADPH oxidase, a key mediator of oxidative cardiac damage and remodelling, modulates anthracycline clinical cardiotoxicity. Purpose Single nucleotide polymorphisms (SNPs) of NADPH oxidase genes could lead to interindividual differences in treatment outcome in acute myeloid leukaemia (AML) patients. Material and methods The main three NADPH oxidase polymorphisms (CYBA:rs4673, NCF4:rs1883112 and RAC2:rs13058338) were evaluated in 225 adult patients at the initial diagnosis of AML using a mass spectrometry based multiplex genotyping assay (Sequenom). All patients received induction chemotherapy consisting of idarubicin plus cytarabine (PETHEMA 99, 2007 and 2010 trials). The efficacy…

Early Detection of Cardiac Damage

2018

Early detection and quantification of cardiac damage in cancer patients are essential to readily intervene with cardioprotective strategies and avoid the need of the discontinuation of antineoplastic treatment.

Cardiovascular Damage Induced by Anti-BCR-ABL TKIs

2018

Anti-BCR-ABL TKIs (tyrosine kinase inhibitors) are drugs that inhibit BCR ABL tyrosine. They are used especially in the treatment of hematological cancer and gastrointestinal stromal tumors (GIST). Anti-BCR-ABL TKIs include first (imatinib), second (nilotinib, dasatinib, bosutinib) and third-generation drugs (ponatinib). Especially second- and third-generation drugs can cause cardiovascular complications such as arterial thrombosis, myocardial ischemia, peripheral arterial diseases, QTc prolongation, and pulmonary hypertension. Nilotinib and ponatinib can cause thrombotic arterial events with various mechanisms. Particularly dasatinib can cause pulmonary hypertension. Compared to convention…

Assessing the Relationship Between Dose-Volume Histogram Parameters and Late Rectal Toxicity in HDR Brachytherapy for Prostate Cancer

2017

Three-dimensional conformal radiotherapy in localized carcinoma of prostate: preliminary reports of toxicity in dose-escalation treatment

2007

Purpose Many studies confirmed the evidence of a dose-response relationship in prostate cancer. Escalation of dose using conventional techniques is however limited by rectal tolerance. IMRT and 3D-CRT have been designed to allow dose escalation while not exceeding rectal tolerance. We evaluated the acute and early late tolerance to surrounding organs upon dose escalation from 70 to 78 Gy in 3D-CRT setting, in order to introduce the IMRT process as a routine practice in prostate cancer treatment. Materials and Methods We compared clinical data from 35 patients with localized adenocarcinoma of the prostate, who received 70 Gy within a traditional reconstructed three-dimensional treatment plan…