title: Discovery and development of clofarabine: a nucleoside analogue for treating cancer.
abstract: The treatment of acute leukaemias, which are the most common paediatric cancers, has improved considerably in recent decades, with complete response rates approaching approximately 90% in some cases. However, there remains a major need for treatments for patients who do not achieve or maintain complete remission, for whom the prognosis is very poor. In this article, we describe the challenges involved in the discovery and development of clofarabine, a second-generation nucleoside analogue that received accelerated approval from the US FDA at the end of 2004 for the treatment of paediatric patients 1-21 years old with relapsed or refractory acute lymphoblastic leukaemia after at least two prior regimens. It is the first such drug to be approved for paediatric leukaemia in more than a decade, and the first to receive approval for paediatric use before adult use.
authors.affiliation: Genzyme, 4545 Horizon Hill Boulevard, San Antonio, Texas 78229, USA. peter.bonate@genzyme.com
authors.forename: Peter L
authors.initials: PL
authors.lastname: Bonate
authors.forename: Larry
authors.initials: L
authors.lastname: Arthaud
authors.forename: William R
authors.initials: WR
authors.lastname: Cantrell
authors.forename: Katherine
authors.initials: K
authors.lastname: Stephenson
authors.forename: John A
authors.initials: JA
authors.lastname: Secrist
authors.forename: Steve
authors.initials: S
authors.lastname: Weitman
mesh_terms: D000227:Adenine Nucleotides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001087:Arabinonucleosides / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D000077866:Clofarabine; D017277:Drug Approval; D015195:Drug Design; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine