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Chemotherapy in pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Doxorubicin is indicated in the treatment of many cancers, including, but not limited to, breast cancer, HL, and NHL, soft-tissue sarcoma, ovarian cancer, lung cancer, bladder cancer, thyroid cancer, and gastric cancer. The drug is an anthracycline antibiotic isolated from Streptomyces species. It intercalates into DNA, which inhibits DNA synthesis. Doxorubicin also inhibits transcription, by inhibiting DNA-dependent RNA polymerase, and the function of topoisomerase II. Myelosuppression is dose limiting, but both acute and chronic cardiotoxicity have been well described. When given in the first trimester, in combination with other agents, doxorubicin has been associated with imperforate anus, rectovaginal fistula, and microcephaly (80). In the largest series to date, Hahn et al. reported on the use of doxorubicin in combination with 5-FU, and cyclophosphamide in 57 pregnant women (81). They reported three congenital anomalies, including Down syndrome, clubfoot, and bilateral ureteral reflux. Several others have reported the use of doxorubicin alone or in combination with other therapies, starting as early as the second trimester, without obvious effects on the fetus. There have been no reports of fetal or infant cardiotoxicity associated with doxorubicin use in pregnancy (67,82,83).
Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Daunorubicin (ZentivaTM) was originally isolated from the fermentation broth of Streptomyces peucetius and is an important agent for the treatment of acute lymphocytic and myelocytic leukemias. It differs in structure from doxorubicin only in the loss of a hydroxy functional group from the acetyl side chain on the D-ring. Administered intravenously, its general physicochemical and clinical properties, and side-effect profile, are not surprisingly similar to those of doxorubicin. In the UK it is approved for use in acute myelogenous leukemia (AML) and acute lymphocytic leukemia (ALL). An intravenous liposomal formulation (DaunoXomeTM) is also approved for the treatment of advanced AIDS-related Kaposi’s sarcoma.
Drug Analysis of Protein Microspheres: From Pharmaceutical Preparation to In Vivo Fate
Published in Neville Willmott, John Daly, Microspheres and Regional Cancer Therapy, 2020
Jeffrey Cummings, David Watson, John F. Smyth
Daunorubicin (daunomycin, rubidomycin) was the first anthracycline antibiotic to be discovered (in 1963) followed by doxorubicin (adriamycin) (in 1969), and together these two remain the most useful clinically.5 Both drugs are used extensively in combination chemotherapy, with doxorubicin having the wider spectrum of clinical activity. Both exhibit the classic toxicity profiles of cytotoxic drugs: nausea and vomiting, gastrointestinal tract toxicity, hair loss, and myelosuppression. In addition, they induce a unique toxicity to the heart, which is related to cumulative dose and peak plasma drug concentrations and is irreversible. Originally, this cardiotoxicity stimulated the drive for new compounds and analog development, but drug resistance, both in the form of the multidrug resistance phenotype6,7 and the atypical (altered topoisomerase II) multidrug resistance phenotype,8 is generally considered the major clinical problem to be overcome by the pharmacologist. Cardiotoxicity can be controlled by altering dose schedules without loss of anticancer activity.9 Because doxorubicin is the more active drug and has been incorporated in microspheres, the following sections will deal exclusively with doxorubicin.
Serum Levels Evaluation of TMSB10 and Endocan in Breast Cancer Patients and In-Vitro Study of Chrysin Effect on These Markers in MCF-7 cell line
Published in Egyptian Journal of Basic and Applied Sciences, 2023
Nada E. Hammouda, Yara A. Samra, Ziad Emarah, Amal M. El-Gayar
Doxorubicin (Dox 50 mg/25 mL) intravenous vial was purchased from Ebewe Pharma (Unterach, am Attersee, Austria). The tetrazolium dye assay was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium-bromide (MTT). It was purchased from SERVA Electrophoresis GmbH (Heidelberg, Germany). DMSO (dimethyl sulfoxide) was obtained from Sigma–Aldrich (St. Louis, MO, USA). Trypsin-Versene (EDTA) Mix (1×), PBS-1× (Phosphate buffered Saline), penicillin–streptomycin stock antibiotic and DMEM (Dulbecco’s Modified Eagle’s Medium) were obtained from Lonza Verviers SPRL, Belgium. Sterile-filtered fetal bovine serum (FBS) was obtained from Life Science Group, UK. All other chemicals were of high analytical grade. Chrysin was purchased from Sigma Aldrich (Darmstadt, Germany) with CAS number c80105-25 G. It was weighted and dissolved in DMSO to prepare a concentration of 6.25, 12.5, 25, and 50 µg/mL.
Molecular design, synthesis and biological evaluation of novel 1,2,5-trisubstituted benzimidazole derivatives as cytotoxic agents endowed with ABCB1 inhibitory action to overcome multidrug resistance in cancer cells
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Abeer H. A. Abdelhafiz, Rabah A. T. Serya, Deena S. Lasheen, Nessa Wang, Mansour Sobeh, Michael Wink, Khaled A. M. Abouzid
Doxorubicin (Dox) is one of the well-established anticancer drugs used in the treatment of different types of cancer, including leukaemia, breast, lung, gastric and paediatric cancers37. Additionally, it is commonly used as reference cytotoxic agent in different biological evaluation tests, especially cytotoxicity assays. However, cancer cells which are treated with doxorubicin acquire multidrug resistance after some time of treatment38. Acute and/or delayed toxicities or even both, have been reported in patients receiving doxorubicin in addition to dangerous side effects including bone marrow depression, cardiomyopathy and sever diarrhea39. Therefore, one of the main concerns should be the use of lower doses of doxorubicin to decrease such destructive side effects.
What’s the latest with investigational drugs for soft tissue sarcoma?
Published in Expert Opinion on Investigational Drugs, 2022
Elena Cojocaru, Andrea Napolitano, Cyril Fisher, Paul Huang, Robin L Jones, Khin Thway
The LMS-04 further compared in a randomized fashion the combination of single-agent doxorubicin versus doxorubicin with trabectedin followed by maintenance with trabectedin alone in first-line therapy for non-progressive patients, with a diagnosis of metastatic or unresectable leiomyosarcoma. The results presented at the European Society for Medical Oncology (ESMO) meeting in 2021 and published in Lancet oncology in 2022, showed that the combination arm has a significantly improved PFS of 12.2 months compared to the doxorubicin arm, where the PFS was 6.2 months [55]. Although the overall survival (OS) data is immature,) the initial reports suggest that OS was significantly longer in the trabectedin plus doxorubicin arm compared to the single agent doxorubicin (30.5 months vs 24.1 months for doxorubicin), with a hazard ratio (HR) of 0.74 [0.49;1.12] in favor of combination therapy followed by maintenance trabectedin [56]. In terms of side effects, 46% of patients receiving doxorubicin alone had a grade 3–4 toxicity including one toxic death, whereas 81% of patients receiving the combination therapy had a grade 3–4 toxicity, mostly hematologic and digestive. The remarkable results of this combination arm of doxorubicin and trabectedin, especially in patients with uterine leiomyosarcoma, reported in both LMS-02 and LMS-04 studies, could potentially change the standard of care in 1st line metastatic treatment for patients with (uterine) leiomyosarcoma [53,56], although whether the combination of the two treatments provides longer survival than its sequence remains to be ascertained [55].