Laromustine (cloretazine)

Abstract

Importance of the field: 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.

Areas covered in this review: 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.

What the reader will gain: 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.

Take home message: 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.

Keywords::

• acute myeloid leukemia
• alkylating agents
• elderly
• induction chemotherapy
• myelodysplastic syndrome