Laromustine (cloretazine).
BACKGROUND
In spite of the recent progress, the prognosis of acute myelogenous leukemia (AML) remains poor, particularly in patients with relapsed disease and in the elderly. In these situations, there is at present no standard of care, and new drugs are urgently needed.


METHODS
Preclinical and clinical studies of Laromustine (formerly cloretazine, VNP-40101M), a new sulfonylhydrazine alkylator, in AML published between 2000 and September 2009 are presented and discussed.


RESULTS
Mechanisms of action of Laromustine and preclincal data that support the rationale for its use in patients with AML are summarized. Laromustine has limited extramedullary toxicity. In Phase II studies, it produced 32% complete responses in elderly patients with previously untreated AML. In a Phase III comparative study of its combination with cytarabine in relapsed AML, increased response rate was offset by excessive toxicity.


CONCLUSIONS
Laromustine has significant activity in AML. As a single agent, laromustine may represent an alternative to conventional treatments for elderly patients. Although significant activity was seen, safety and optimal dosing in combination regimen remain to be established and are now being investigated.
Vey
Norbert
N
Unité d'Hématologie 3, Institut Paoli-Calmettes, Department of Hematology, 232 Blvd Sainte Marguerite, 13009 Marseille, France. veyn@marseille.fnclcc.fr
Giles
Frank
F
D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006834:Hydrazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000378:metabolism; D012074:Remission Induction; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D006834:Hydrazines; D013449:Sulfonamides; C483604:laromustine