The nucleoside analog sapacitabine appears to be "active and tolerable" in elderly patients with acute myeloid leukemia (AML), say authors of a phase II study reported in the Lancet Oncology.
A third of patients given a 400 mg dosing regimen of the drug were still alive at the 1-year follow up, notes the team, and the majority of nonhematologic toxicities observed in the cohort were gastrointestinal in nature and mostly mild to moderate.
"Outcome for elderly patients with AML is poor," write Hagop Kantarjian (University of Texas, MD Anderson Cancer Center, Houston, USA) and colleagues. "The development of novel drugs with new mechanisms of action, improved anti-leukaemic activity, and more favourable safety profiles is much needed," they add.
A total of 105 AML patients aged a median of 77 years took part in the study, of whom 60 were randomly assigned to either sapacitabine 200 mg twice per day for 7 days (group A), 300 mg twice per day for 7 days (group B), or 400 mg twice per day for 3 days per week for 2 weeks, each repeated every 28 days.
Once these initial 60 patients had completed a treatment cycle, at least four had achieved complete response (CR) or CR with incomplete blood count recovery, and the 30-day death rate was 20% or less, the groups were expanded to include the remainder of the cohort. Group B did not satisfy these criteria.
Median overall survival was 197, 102, and 213 days in groups A, B, and C, respectively, with a corresponding 35%, 10%, and 30% of these groups alive at the 1-year follow-up point.
While overall 1-year survival appears similar in groups A and C, rates in group A's "expanded" cohort were low, at just 10%. Conversely, expanded group C's rates were similar to the initial randomized group's rates, at 24%.
"Overall, therefore, the 400 mg dose schedule seems to have a better efficacy profile than the 200 mg and 300 mg dose schedules," remark Kantarjian et al.
The most common grade 3-4 adverse events were anemia, neutropenia, thrombocytopenia, febrile neutropenia, and pneumonia, report the authors, and gastrointestinal symptoms (90% of which were grade 1-2) only resulted in a 2% dose reduction.
"If one or more such low-intensity therapies are shown to be active and safe, combined modality therapies could improve the outcome in this poor-prognosis group," conclude the researchers.
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