Cancer Therapies and Cardiac Dysfunction
Andreas P. Kalogeropoulos, Hal A. Skopicki, Javed Butler in Heart Failure, 2023
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
Vincenzo Berghella in Maternal-Fetal Evidence Based Guidelines, 2022
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].
Breast cancer and pregnancy
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Adjuvant or neoadjuvant chemotherapy is potentially teratogenic to the fetus in the first trimester of pregnancy (45), with an estimated risk of fetal malformations of up to 17% when administered during the first trimester (8). If it is felt unsafe to delay adjuvant therapy until after delivery, chemotherapy can be considered in the second and third trimesters. The anthracyclines doxorubicin (46) and epirubicin (47), as well as taxanes (48), appear relatively safe, with the few series available reporting a 0% to 6% death rate (intrauterine, stillbirth, or neonatal) after treatment. It is postulated that placental P-glycoprotein may limit the transplacental transfer of these agents. Chemotherapy should be administered at least 3 weeks before delivery to avoid sepsis and bleeding in a mother with low red blood cell, white blood cell, and platelet counts (28). Trastuzumab use to treat HER-2-positive PABC was associated with anhydramnios in three of six women and should be avoided during pregnancy since it appears to interfere with the normal development of the fetal kidney (48). Lactation should be suppressed during chemotherapy to prevent agent transmission to the infant (49). The long-standing recommendation to avoid pregnancy for 2 years after a diagnosis of breast cancer is being questioned, since median time to relapse is more than 5 years, even for patients with stage II node-positive disease who receive standard-of-care regimens of surgery and adjuvant therapy (50).
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.
Early mortality continues to be a barrier to excellent survival in childhood acute promyelocytic leukemia: a retrospective study of 62 patients spanning 17 years
Published in Pediatric Hematology and Oncology, 2023
Pritam Singha Roy, Vinay Munikoty, Amita Trehan, Richa Jain, Prateek Bhatia, Shano Naseem, Neelam Varma, Deepak Bansal
Patients were classified based on the white blood cell (WBC) count at diagnosis as standard (WBC <10 × 109/L) or high-risk (WBC ≥10 × 109/L).11 Patients were treated with ATRA and chemotherapy-based protocol. Treatment included induction followed by three courses of consolidation and two years of maintenance chemotherapy. The protocol was updated in 2015. The treatment protocols administered during 2003–2015 and 2015–2021 are listed and compared in Table 1. In order to augment the therapeutic efficacy for HR patients and reduce treatment-related toxicity for SR patients, the protocol was amended as follows: (a) central nervous system (CNS) prophylaxis with intrathecal cytarabine for all patients, (b) reduction in the cumulative dose of anthracyclines and risk-stratified dosing, and (c) inclusion of ATRA in all the cycles of consolidation.12 In addition, the diagnostic cerebrospinal fluid (CSF) was rescheduled to the end of induction instead of at the vulnerable timepoint of diagnosis.
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.