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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Administered either orally or by intravenous or intraperitoneal injection, treosulfan is commercially available in Europe for the treatment of ovarian cancer, although it was not similarly approved by the FDA. In Europe it is used in combination with fludarabine as part of a conditioning treatment prior to allogeneic hematopoietic stem cell transplantation (alloHSCT) in adult patients with malignant and nonmalignant diseases, and in pediatric patients older than one month. The TrecondiTM brand, produced by the German company Medac, received EU-wide approval for this purpose in 2019.
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Published in Caroline Ashley, Aileen Dunleavy, John Cunningham, The Renal Drug Handbook, 2018
Caroline Ashley, Aileen Dunleavy, John Cunningham
Treosulfan is a prodrug of a bifunctional alkylating agent, converted in vivo to epoxide compounds. Approximately 30% of the substance is excreted unchanged in the urine within 24 hours, nearly 90% of which is within the first 6 hours after administration.
Paediatric oncology
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2014
Stephen Lowis, Rachel Cox, John Moppett, Antony Ng
In his original reports of diffuse endothelioma of bone, Ewing described the radiosensitivity of the tumour,158 although with radiotherapy alone, the large majority of patients relapsed with disseminated disease within 2–5 years. Numerous agents have been shown to have activity against Ewing’s tumour including cyclophosphamide, doxorubicin, ifosfamide, vincristine, actinomycin D, busulphan, melphalan, BCNU and 5-fluorouracil. Etoposide and ifosfamide administered in combination have been reported to have high activity.159,160 Topoisomerase-I inhibitors, temozolomide, treosulfan, gemcitabine and docetaxol have also been identified to yield promising response in these patients. Combination chemotherapy has been used for many years, and OS has progressively increased. It is clear, however, that cure cannot be achieved by systemic chemotherapy alone, and local therapy (surgery and/or radiotherapy) is required to control disease at the primary site.161 The issues of chemotherapy, radiotherapy and surgery have been addressed in the major national and international trials, and it is appropriate to discuss these here.
Acute toxicity and outcome among pediatric allogeneic hematopoietic transplant patients conditioned with treosulfan-based regimens
Published in Pediatric Hematology and Oncology, 2020
Pasi Huttunen, Mervi Taskinen, Kim Vettenranta
Treosulfan is a pro-drug (L-treitol-1,4-bis-methanesulfonate, dihydroxybusulfan), and initially used for the treatment of solid tumors such as ovarian cancer. It renders a myeloablative effect on both the committed and non-committed stem cells.10 During the past several years, it has emerged as a feasible option with a potentially lower toxicity. Yet, pediatric data on its acute toxicity remain limited as well as studies comparing treosulfan-based conditioning to other non-TBI and TBI-conditioning regimens. The aim of this retrospective study was to analyze the acute toxicity of treosulfan-based conditioning regimens and compare it with the busulfan- and TBI-based conditioning regimens.
Comparison of Hematopoietic Stem Cell Transplantation Results in Patients with β-Thalassemia Major from Three Different Graft Types
Published in Hemoglobin, 2021
Selime Aydogdu, Ersin Toret, Basak A. Aksoy, Muhammed Fatih Aydın, Funda E. Cipe, Ceyhun Bozkurt, Tunc Fisgin
Patients received myeloablative conditioning (MAC) consisting treosulfan (in 44 transplants) [until April 2018, intravenous busulfan was used instead of treosulfan (in 42 transplants)], fludarabine, cyclophosphamide, anti-thymocyte globulin-Fresenius (ATG-F) and thiotepa. Myeoloablative conditioning regimen consisted of treosulfan 14 mg/m2 daily (day −8 to −6) [intravenous busulfan 0.8–1.15 mg/kg (day −9 to −6)], fludarabine 30 mg/m2 daily (day −9 to −4), thiotepa 10 mg/kg daily (day −2), cyclophosphamide 50 mg/kg daily (day −3 to −2) and ATG-F 15 mg/kg daily (day −2 to 0).
The current and future role of stem cells in myelodysplastic syndrome therapies
Published in Expert Review of Hematology, 2018
Guido Kobbe, Thomas Schroeder, Rainer Haas, Ulrich Germing
Recently so-called toxicity-reduced conditioning regimens have been described [85–87]. The term has been used almost exclusively for regimens utilizing high-dose treosulfan. This drug has become popular as it is characterized by high efficacy and low toxicity when used in high-dose regimens for aBSCT in AML and MDS [88]. Recently a randomized study comparing a busulfan based RIC regimen with fludarabine plus treosulfan in AML in first CR was terminated because of at least non-inferior results in the treosulfan arm [89].