Clinical activity of laromustine (Onrigin) in hematologic malignancies

Yesid Alvarado, Ronan Swords, Kevin R. Kelly, Francis J. Giles

Research output: Contribution to journalReview article

2 Scopus citations

Abstract

Laromustine (Onrigin),formerly known as Cloretazine ® (VNP40101M), belongs to a novel class of alkylating agents - the sulfonylhydrazines - and was selected for clinical development based on its broad anti-tumor activity in preclinical models. Laromustine is metabolized to yield 90CE and methylisocyanate, the former rapidly produces an alkylating, chloroethylating species, similar to the chloroethylating species generated by carmustine. However, several features distinguish laromustine from carmustine and possibly account for their biological differences in vitro and in vivo. The chloroethylating species responsible for laromustines alkylator effect is relatively specific for guanine and forms a crosslink after incorporation into DNA. Laromustine has significant activity in both older patients with previously untreated acute myeloid leukemia or high-risk myelodysplastic syndrome, including those with very poor-risk disease, and in patients with relapsed disease. Further clinical studies are required with laromustine to evaluate its place as an anticancer agent in other hematological malignancies.

Original languageEnglish (US)
Pages (from-to)481-488
Number of pages8
JournalExpert Review of Hematology
Volume2
Issue number5
DOIs
StatePublished - Dec 1 2009

Keywords

  • Alkylating agents
  • AML
  • ATG
  • Carbamoylation
  • Chloroethylation
  • Cloretazine
  • Laromustine
  • Leukemia
  • Onrigin
  • SHP
  • Sulfonylhydrazine prodrug
  • VNP40101M

ASJC Scopus subject areas

  • Hematology

Fingerprint Dive into the research topics of 'Clinical activity of laromustine (Onrigin<sup>™</sup>) in hematologic malignancies'. Together they form a unique fingerprint.

  • Cite this