title: Pharmacology of dimethanesulfonate alkylating agents: busulfan and treosulfan.
abstract: BACKGROUND
  Among the dimethanesulfonates, busulfan, in combination with other alkylating agents or nucleoside analogues, is the cornerstone of high-dose chemotherapy. It is used, and followed hematopoietic stem cell transplantation, for the treatment of various hematologic malignancies and immunodeficiencies. Treosulfan, which is a hydrophilic analogue of busulfan, was the first dimethanesufonate registered for the treatment of ovarian cancer. Recently, treosulfan has been investigated for the treatment of hematologic malignancies in combination with the same second agents before hematopoietic stem cell transplantation.
  
  
  METHODS
  This work reviews the pharmacological data of these two dimethanesulfonates alkylating agents. Specifically, the article looks at their chemistry, metabolism, anticancer activity, and their pharmacokinetics and pharmacodynamics.
  
  
  CONCLUSIONS
  Busulfan has been investigated widely for more than three decades leading to a large and precise handling of this agent with numerous studies on activity and pharmacokinetics and pharmacodynamics. In contrast, the behavior of treosulfan is still under investigation and not fully described. The complexity of treosulfan's metabolism and mechanism of action gives rise to the need of a deeper understanding of its pharmacological activity in a context of high-dose chemotherapy. Specifically, there is a great need to better understand its pharmacokinetics/pharmacodynamics relationship.
authors.affiliation: Collège de France, Center for Interdisciplinary Research in Biology, CNRS UMR 7241, INSERM U 1050, MEMOLIFE Laboratory of Excellence & Paris Science et Lettres Research University, Paris, France.
authors.forename: Ariane
authors.initials: A
authors.lastname: Galaup
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002066:Busulfan / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D003520:Cyclophosphamide / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D019337:Hematologic Neoplasms / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D019653:Myeloablative Agonists / Q000627:therapeutic use; D010051:Ovarian Neoplasms / Q000188:drug therapy; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation / Q000379:methods
chemical_list: D018906:Antineoplastic Agents, Alkylating; D019653:Myeloablative Agonists; D003520:Cyclophosphamide; C018404:treosulfan; D014740:Vidarabine; D002066:Busulfan; C024352:fludarabine