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A phase 1-2 study of a farnesyltransferase inhibitor, tipifarnib, combined with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome
Article first published online: 19 OCT 2010
Copyright © 2010 American Cancer Society
Volume 117, Issue 6, pages 1236–1244, 15 March 2011
How to Cite
Jabbour, E., Kantarjian, H., Ravandi, F., Garcia-Manero, G., Estrov, Z., Verstovsek, S., O'Brien, S., Faderl, S., Thomas, D. A., Wright, J. J. and Cortes, J. (2011), A phase 1-2 study of a farnesyltransferase inhibitor, tipifarnib, combined with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome. Cancer, 117: 1236–1244. doi: 10.1002/cncr.25575
- Issue published online: 4 MAR 2011
- Article first published online: 19 OCT 2010
- Manuscript Accepted: 13 MAY 2010
- Manuscript Revised: 11 MAR 2010
- Manuscript Received: 16 NOV 2009
- acute myeloid leukemia;
- myelodysplastic syndrome;
- farnesyl transferase inhibitor
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 high-risk myelodysplastic syndrome.
Induction consisted of idarubicin 12 mg/m2 a day on days 1-3, cytarabine 1.5 g/m2 intravenously continuously daily on days 1-4 (days 1-3 if age ≥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/m2 a day on days 1-2, cytarabine 0.75 g/m2 a day on days 1-3, and tipifarnib 300 mg twice a day for 14 days every 4-6 weeks. Maintenance with tipifarnib 300 mg twice a day for 21 days every 4-6 weeks was continued for 6 months.
With a median follow-up 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.
The combination of IA and tipifarnib is safe and active. Further studies exploring different dosages and schedules are warranted, particularly in patients with poor-risk AML. Cancer 2011. © 2010 American Cancer Society.