The Pharmaceutical Journal
Vol 278 No 7435 p68
20 January 2007

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Two new drugs show promising results for AML

Two drugs in development to treat acute myeloid leukaemia (AML) have shown promising results in poor-prognosis disease in early clinical trials. Both drugs have been developed through redesign of the chemical structure of currently available agents in an effort to achieve a better efficiency profile. The studies are reported this month in the Journal of Clinical Oncology (2007;25:10 and 25).

Troxacitabine is a nucleoside analogue with a long half-life that is excreted largely unchanged. It also has special features of cellular uptake and intracellular metabolism, bypassing the resistance mechanism imposed in nucleoside-specific membrane transporters.

Researchers gave a continuous infusion of troxacitabine to 48 poor-prognosis, heavily pretreated patients with AML and a median age of 58 years. They found that this regimen allowed a significant increase in dose intensity compared with iv bolus. An overall remission rate of 15 per cent was achieved. The maximum tolerated dose was 12mg/m²/day for five days.

In the second study, an iv bolus of cloretazine, a sulfonylhydrazine alkylating agent with significant antileukaemia activity, was given to 104 older patients with previously untreated AML or high-risk myelodysplastic syndrome and co-morbidities. A remission rate of 32 per cent was achieved after one or two courses of therapy.

The author of an accompanying editorial (ibid, p1) says that, considering the poor risk profile of the patients, these drugs deserve additional study.