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 - PubMed (original) (raw)
Clinical Trial
. 2011 Mar 15;117(6):1236-44.
doi: 10.1002/cncr.25575. Epub 2010 Oct 19.
Affiliations
- PMID: 20960519
- PMCID: PMC4061136
- DOI: 10.1002/cncr.25575
Clinical Trial
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
Elias Jabbour et al. Cancer. 2011.
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 high-risk myelodysplastic syndrome.
Methods: Induction consisted of idarubicin 12 mg/m(2) a day on days 1-3, cytarabine 1.5 g/m(2) 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/m(2) a day on days 1-2, cytarabine 0.75 g/m(2) 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.
Results: 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.
Conclusions: 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.
Copyright © 2010 American Cancer Society.
Figures
Figure 1
Survival and remission duration are shown.
Figure 2
Remission duration with idarubicin and cytarabine versus with idarubicin, cytarabine, and tipifarnib (including patients in CR and CRp) is shown.
Figure 3
Overall survival idarubicin and cytarabine versus with idarubicin, cytarabine, and tipifarnib is shown.
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