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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

  1. Elias Jabbour MD,
  2. Hagop Kantarjian MD,
  3. Farhad Ravandi MD,
  4. Guillermo Garcia-Manero MD,
  5. Zeev Estrov MD,
  6. Srdan Verstovsek MD,
  7. Susan O'Brien MD,
  8. Stefan Faderl MD,
  9. Deborah A. Thomas MD,
  10. John J. Wright MD,
  11. Jorge Cortes MD†,*

Article first published online: 19 OCT 2010

DOI: 10.1002/cncr.25575

Issue

Cancer

Cancer

Volume 117, Issue 6, pages 1236–1244, 15 March 2011

Additional Information

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

Author Information

  1. Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas

  1. †

    Fax: (713) 794-4297

*Department of Leukemia, The University of Texas, M. D. Anderson Cancer Center, 1515 Holcombe Blvd., PO Box 428, Houston, TX 77030

  1. †

    Fax: (713) 794-4297

Publication History

  1. Issue published online: 4 MAR 2011
  2. Article first published online: 19 OCT 2010
  3. Manuscript Accepted: 13 MAY 2010
  4. Manuscript Revised: 11 MAR 2010
  5. Manuscript Received: 16 NOV 2009

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Keywords:

  • acute myeloid leukemia;
  • tipifarnib;
  • combination;
  • myelodysplastic syndrome;
  • farnesyl transferase inhibitor

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/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.

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. Cancer 2011. © 2010 American Cancer Society.

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