Clinical activity of laromustine (Onrigin) in hematologic malignancies

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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

Fingerprint

Hematologic Neoplasms
Carmustine
Alkylating Agents
laromustine
Myelodysplastic Syndromes
Guanine
Acute Myeloid Leukemia
Antineoplastic Agents
DNA

Keywords

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

ASJC Scopus subject areas

  • Hematology

Cite this

Clinical activity of laromustine (Onrigin) in hematologic malignancies. / Alvarado, Yesid; Swords, Ronan T; Kelly, Kevin R.; Giles, Francis J.

In: Expert Review of Hematology, Vol. 2, No. 5, 01.12.2009, p. 481-488.

Research output: Contribution to journalArticle

Alvarado, Yesid ; Swords, Ronan T ; Kelly, Kevin R. ; Giles, Francis J. / Clinical activity of laromustine (Onrigin) in hematologic malignancies. In: Expert Review of Hematology. 2009 ; Vol. 2, No. 5. pp. 481-488.
@article{e7a1e38d655f44b3830de2e721ff6c69,
title = "Clinical activity of laromustine (Onrigin™) in hematologic malignancies",
abstract = "Laromustine (Onrigin™),formerly known as Cloretazine {\circledR} (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.",
keywords = "Alkylating agents, AML, ATG, Carbamoylation, Chloroethylation, Cloretazine, Laromustine, Leukemia, Onrigin, SHP, Sulfonylhydrazine prodrug, VNP40101M",
author = "Yesid Alvarado and Swords, {Ronan T} and Kelly, {Kevin R.} and Giles, {Francis J.}",
year = "2009",
month = "12",
day = "1",
doi = "10.1586/ehm.09.38",
language = "English",
volume = "2",
pages = "481--488",
journal = "Expert Review of Hematology",
issn = "1747-4086",
publisher = "Expert Reviews Ltd.",
number = "5",

}

TY - JOUR

T1 - Clinical activity of laromustine (Onrigin™) in hematologic malignancies

AU - Alvarado, Yesid

AU - Swords, Ronan T

AU - Kelly, Kevin R.

AU - Giles, Francis J.

PY - 2009/12/1

Y1 - 2009/12/1

N2 - 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.

AB - 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.

KW - Alkylating agents

KW - AML

KW - ATG

KW - Carbamoylation

KW - Chloroethylation

KW - Cloretazine

KW - Laromustine

KW - Leukemia

KW - Onrigin

KW - SHP

KW - Sulfonylhydrazine prodrug

KW - VNP40101M

UR - http://www.scopus.com/inward/record.url?scp=77953393181&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953393181&partnerID=8YFLogxK

U2 - 10.1586/ehm.09.38

DO - 10.1586/ehm.09.38

M3 - Article

C2 - 21083013

AN - SCOPUS:77953393181

VL - 2

SP - 481

EP - 488

JO - Expert Review of Hematology

JF - Expert Review of Hematology

SN - 1747-4086

IS - 5

ER -