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

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

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

R A Mesa,J K Camoriano,S M Geyer,W Wu,S H Kaufmann,C E Rivera,C Erlichman,J Wright,A Pardanani,T Lasho,C Finke,C Y Li,A Tefferi,

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 x 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 JAK2(V617F) levels or tipifarnib IC(50) 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.

A phase II trial of tipifarnib in myelofibrosis: primary, post-polycythemia vera and post-essential thrombocythemia. Publishing Authors By Initials

RA Mesa,JK Camoriano,SM Geyer,W Wu,SH Kaufmann,CE Rivera,C Erlichman,J Wright,A Pardanani,T Lasho,C Finke,CY Li,A Tefferi,

For similar diagnosis: prognosis: treatment outcome research abstracts see: diagnosis: prognosis: treatment outcome research

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

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Leukemia : official journal of the Leukemia Societ

VOLUME: 21

Page Numbers: 1964-70

Journal Abbreviation: Leukemia

ISSN: 0887-6924

DAY: 21

MONTH: 06

YEAR: 2007

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

Number of References:

LANGUAGE: eng

NlmUniqueID: 8704895

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

KEYWORDS: Treatment Outcome

MESH TERMS: genetics

Chemical & Substance for Abstract: A phase II trial of tipifarnib in myelofibrosis: primary, post-polycythemia vera and post-essential thrombocythemia. Information

Substance Name: Janus Kinase 2

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for A phase II trial of tipifarnib in myelofibrosis: primary, post-polycythemia vera and post-essential thrombocythemia.

AFFILIATION: Division of Hematology, Rochester, MN, USA. mesa.ruben@mayo.edu

Country: England

AGENCY: United States NCI

GRANT: N01CM62205

ACRONYM: CM

MEDLINETA: Leukemia

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