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Chronic Myeloproliferative Disorder

A phase II trial of tipifarnib in myelofibrosis: primary, post-polycythemia vera and post-essential thrombocythemia

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Abstract

Patients with primary myelofibrosis (PMF) or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (post-PV/ET MF) have limited therapeutic options. The farnesyltransferase-inhibitor tipifarnib inhibits in vitro proliferation of myeloid progenitors from such patients. In the current phase II clinical trial, single-agent oral tipifarnib (300 mg twice daily × 21 of 28 days) was given to 34 symptomatic patients with either PMF (n=28) or post-PV/ET MF (n=6). Median time to discontinuation of protocol therapy was 4.6 months; reasons for early termination (n=19; 56%) included disease progression (21%) and adverse drug effects (18%). Toxicities (⩾grade 3) included myelosuppression (n=16), neuropathy (n=2), fatigue (n=1), rash (n=1) and hyponatremia (n=1). Response rate was 33% for hepatosplenomegaly and 38% for transfusion-requiring anemia. No favorable changes occurred in bone marrow fibrosis, angiogenesis or cytogenetic status. Pre- and post-treatment patient sample analysis for in vitro myeloid colony growth revealed substantial reduction in the latter. Clinical response did not correlate with either degree of colony growth, measurable decrease in quantitative JAK2V617F levels or tipifarnib IC50 values (median 11.8 nM) seen in pretreatment samples. The current study indicates both in vitro and in vivo tipifarnib activity in PMF and post-PV/ET MF.

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Acknowledgements

We acknowledge the support of both the Phase II Consortium and the Cancer Therapy and Evaluation Program (CTEP) of the National Cancer Institute. This study was supported by grants CA15083 and N01CM62205.

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Authors and Affiliations

  1. Division of Hematology, Rochester, MN, USA

    R A Mesa, S H Kaufmann, A Pardanani, T Lasho, C Finke & A Tefferi

  2. Division of Hematology, Scottsdale, AZ, USA

    J K Camoriano

  3. Mayo Clinic Cancer Center Statistics, Rochester, MN, USA

    S M Geyer & W Wu

  4. Division of Hematology, Jacksonville, FL, USA

    C E Rivera

  5. Department of Oncology, Mayo Clinic College of Medicine, Rochester, MN, USA

    C Erlichman

  6. Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA

    J Wright

  7. Division of Hematopathology, Mayo Clinic College of Medicine, Rochester, MN, USA

    C Y Li

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  1. R A Mesa
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  2. J K Camoriano
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  3. S M Geyer
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  4. W Wu
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  12. C Y Li
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Correspondence to R A Mesa.

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Mesa, R., Camoriano, J., Geyer, S. et al. A phase II trial of tipifarnib in myelofibrosis: primary, post-polycythemia vera and post-essential thrombocythemia. Leukemia 21, 1964–1970 (2007). https://doi.org/10.1038/sj.leu.2404816

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  • DOI: https://doi.org/10.1038/sj.leu.2404816

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