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Clinical activity of laromustine (Onrigin™) in hematologic malignancies.

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 laromustine's 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.
AuthorsYesid Alvarado, Ronan Swords, Kevin R Kelly, Francis J Giles
JournalExpert review of hematology (Expert Rev Hematol) Vol. 2 Issue 5 Pg. 481-8 (Oct 2009) ISSN: 1747-4094 [Electronic] England
PMID21083013 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents, Alkylating
  • Hydrazines
  • Sulfonamides
  • laromustine
Topics
  • Animals
  • Antineoplastic Agents, Alkylating (pharmacokinetics, pharmacology, therapeutic use)
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical
  • Hematologic Neoplasms (drug therapy)
  • Humans
  • Hydrazines (pharmacokinetics, pharmacology, therapeutic use)
  • Sulfonamides (pharmacokinetics, pharmacology, therapeutic use)

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