Abstract
BACKGROUND:
The authors conducted a phase 1/2 study of tipifarnib in combination with idarubicin and cytarabine (IA) in 95 patients with previously untreated acute myeloid leukemia (AML) or highβrisk myelodysplastic syndrome.
METHODS:
Induction consisted of idarubicin 12 mg/m^2^ a day on days 1β3, cytarabine 1.5 g/m^2^ intravenously continuously daily on days 1β4 (days 1β3 if age β₯60 years), and tipifarnib, with the first cohort (n = 6) receiving 200 mg orally twice a day and all others receiving 300 mg twice a day for 21 days every 28 days. Consolidation consisted of 5 courses of idarubicin 8 mg/m^2^ a day on days 1β2, cytarabine 0.75 g/m^2^ a day on days 1β3, and tipifarnib 300 mg twice a day for 14 days every 4β6 weeks. Maintenance with tipifarnib 300 mg twice a day for 21 days every 4β6 weeks was continued for 6 months.
RESULTS:
With a median followβup of 33 months, 61 patients achieved complete remission (CR) (64%), and 9 achieved complete remission with incomplete platelet recovery (CRp) (9%). The median duration of CR was not reached. Median overall survival was 17 months. The most common grade 3 adverse events were gastrointestinal toxicities, liver dysfunction, and skin rash. Compared with historical IA, IA and tipifarnib showed a better CR duration (P = .04) and a trend toward a higher CR rate in patients with chromosome 5/7 abnormalities.
CONCLUSIONS:
The combination of IA and tipifarnib is safe and active. Further studies exploring different dosages and schedules are warranted, particularly in patients with poorβrisk AML. Cancer 2011. Β© 2010 American Cancer Society.