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Cancer Therapies and Cardiac Dysfunction
Published in Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler, Heart Failure, 2023
Victoria Shklar, Katherine Godfrey, Michelle E. Bloom
Anthracyclines are a class of chemotherapeutics used in the management of many solid and hematologic cancers, most prominently for breast cancer. These drugs, including doxorubicin, daunorubicin, epirubicin, and idarubicin, are responsible for the earliest described form of chemotherapy-induced cardiotoxicity and as such are the most well studied. Anthracyclines rapidly localize to the nucleus where they integrate with DNA, thus disrupting RNA production and DNA metabolism (Figure 29.1). Their cytotoxicity is primarily due to inhibition of topoisomerase II, which then prevents DNA repair and results in apoptosis.29 There are two isozymes of topoisomerase, Top IIa, which is expressed in rapidly dividing cells, and Top IIb, which is expressed in quiescent cells like cardiac myocytes.30 The non-selective nature of anthracyclines results in binding of these agents to Top IIb, resulting in myocyte death.31 Anthracyclines also cause oxidative stress through the formation of reactive oxygen species (ROS), which result in fibrosis and lipid peroxidation of cardiac membranes,32 and may directly impair proliferation of cardiac progenitor cells, thus impairing recovery from stressors and inhibiting pro-survival signaling.33,34
Cancer
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Elyce Cardonick, Charlotte Maggen, Puja Patel
Radiation therapy is usually postponed until postpartum. As the pregnancy advances, the fetus has increased proximity to the breast and radiation field increasing exposure risk. Neoadjuvant chemotherapy with large tumors at presentation allows pathologic evidence of response to therapy which can be prognostic. The regimen used should adhere to the standard recommended chemotherapy regimens in the non-pregnant population [30]. The majority of pregnant women reported in the literature are treated with cyclophosphamide (C), doxorubicin (A) or epirubicin (E), with or without 5-fluouracil (5FU). AC or EC alone are preferable as recent evidence reveals no survival benefit of 5FU in breast cancer patients. A single study reported dose dense AC (every 2 weeks) but majority of case reports and small series administer AC every 3 weeks [44]. Currently doxorubicin is the preferred anthracycline to use during pregnancy and is commonly included in the regimens to treat various types of cancer during pregnancy. Data regarding the use of epirubicin in pregnancy is accumulating in Europe as it has lower myelotoxic and cardiotoxic properties and is better tolerated in non-pregnant patients. Transient neonatal cardiomyopathy has been reported after idarubicin exposure and the use of this anthracycline is not recommended during pregnancy [5, 6].
Neoplasia in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Combination chemotherapy has become the therapeutic management of choice in patients with acute leukemia. Children who were exposed to chemotherapeutic agents in utero showed normal growth and development from 1 to 17 years of age (235). If given after the second trimester, chemotherapy is not associated with an increased rate of fetal malformations (240). Remission rates of pregnant women treated with combination chemotherapy compare favorably with those in comparable nonpregnant women. Standard anti-leukemic agents, such as cytarabine and anthracyclines, can be safely administered during the second and third trimesters. However, antifolates should be avoided during the first trimester, owing to a 10% to 20% risk of congenital anomalies (245). Use of L-asparaginase during pregnancy should always been done with caution as it has been shown to decrease the levels of certain thrombosis inhibitors and is associated with a significantly increased risk of thromboembolism (246–249). It is important to note that evidence shows that delaying appropriate chemotherapy for more than a few weeks at any time other than the latter part of the third trimester is associated with excessive fetal mortality (235,250,251).
Neurotrophic tropomyosin receptor kinase (NTRK) fusion positive tumors: a historical cohort analysis
Published in Expert Review of Anticancer Therapy, 2023
Lauriane Lemelle, Delphine Guillemot, Anne-Laure Hermann, Arnaud Gauthier, Matthieu Carton, Nadège Corradini, Angélique Rome, Pablo Berlanga, Anne Jourdain, Aude Marie Cardine, Sarah Jannier, Hélène Boutroux, Anne Sophie Defachelles, Isabelle Aerts, Birgit Geoerger, Marie Karanian, François Doz, Hervé J Brisse, Gudrun Schleiermacher, Olivier Delattre, Gaëlle Pierron, Daniel Orbach
Clinical data were collected retrospectively from medical files (supplemental material 1). To better characterize the specific outcome, patients were analyzed in three groups: IFS (from soft tissue or kidney congenital mesoblastic nephroma (CMN)), other mesenchymal tumors (Other-MT), and CNS tumors. Histological diagnosis was based on local pathology reports. The group of ‘alkylating drugs’ effects included ifosfamide, cyclophosphamide, high-dose cyclophosphamide, thiotepa, temozolomide, procarbazine, and CCNU. The group of ‘anthracycline drugs’ included only doxorubicin. A ‘mutilating surgery’ was defined as either a major resection or a total organ amputation with functional impairment or a significant esthetic impairment. Long term side effects were graded according to the Common Terminology Criteria for Adverse Events v5.0.
A review of the risks of long-term consequences associated with components of the CHOP chemotherapy regimen
Published in Journal of Drug Assessment, 2022
Crystal Watson, Hemanth Gadikota, Arie Barlev, Rachel Beckerman
For patients exposed to anthracycline, alkylating agents, and corticosteroids as part of their cancer therapy, there is consistent evidence of a significant dose-dependent risk of cardiac toxicity, hormone deficiencies and infertility, t-MDS/AML, osteonecrosis, and bladder cancer. These effects are significant, impact a high percentage of patients, and occur as early as one year after treatment. Cardiac toxicity was seen to impact a notably high proportion of patients treated with anthracycline, with heart failure reported to affect up to 68% of patients and structure and function disorders up to 48%. These effects were seen from as early as one year to as late as 28 years after receiving a primary cancer diagnosis. Hormone deficiencies also impacted a high proportion of patients, affecting up to 60% of male and 83% of female patients at three to five years after treatment with alkylating agents. Significant adverse effects on fertility and lasting reproductive risks were also evident. T-MDS/AML, osteonecrosis, and bladder cancer affected fewer patients (up to 9.7%–11%) but risks persisted over time and were still increased at 20–30 years following treatment.
Linalool exhibits therapeutic and protective effects in a rat model of doxorubicin-induced kidney injury by modulating oxidative stress
Published in Drug and Chemical Toxicology, 2022
Eyup Altinoz, Zulal Oner, Hulya Elbe, Nuray Uremis, Muhammed Uremis
DOX, an antineoplastic drug from the anthracycline family, is used for a variety of neoplasms such as leukemias, lymphomas, and solid tumors. Nephrotoxicity is one of the most important side effects of anthracyclines. Although the mechanism of DOX is not fully understood, DOX causes intrarenal free radical production and changes kidney functions (Deman et al.2001, Öz and İlhan 2006). In the current study, we preferred the dose of DOX corresponds to the dose that is being used in clinical treatment (Chabner et al.2001). The dose of DOX in clinical practice for human (60 kg) is 74 mg/m2. Ajith et al. (2008) reported that single dose of DOX with ip injection caused acute kidney injury in rats that could be improved by Zingiber officinale. Yilmaz et al. (2006) showed that single dose of DOX administration (10 mg/kg) caused acute cardio-renal toxicity after 72 h. In this study, we aimed to investigate the effects of DOX on the kidney by biochemical and histopathological analyses.