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Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed

Thomas E Witzig1, Hui Tang, Ivana N M Micallef

  • 1Division of Hematology, Department of Medicine, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN, USA. witzig@mayo.edu

Blood
|July 5, 2011
PubMed

Insights

Tipifarnib showed activity in relapsed or refractory lymphoma, especially in T-cell and Hodgkin lymphoma (HL/T) types. Further studies of this farnesyltransferase inhibitor are warranted due to its safety profile.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Lymphoma is a heterogeneous group of cancers.
  • Relapsed or refractory lymphoma presents a significant unmet medical need.
  • Farnesyltransferase inhibitors represent a novel therapeutic approach.

Purpose of the Study:

  • To evaluate the efficacy and safety of tipifarnib in adult patients with relapsed or refractory lymphoma.
  • To determine response rates across different lymphoma subtypes.
  • To identify potential predictors of response.

Main Methods:

  • Phase 2, open-label study of tipifarnib (300 mg twice daily) in 93 patients.
  • Patients received treatment in 28-day cycles.
  • Response rates were assessed for aggressive B-cell, indolent B-cell, and T-cell/Hodgkin lymphoma (HL/T) groups.

Main Results:

  • Overall response rates were 17% (aggressive B-cell), 7% (indolent B-cell), and 31% (HL/T).
  • Tipifarnib demonstrated notable activity in T-cell and Hodgkin lymphoma.
  • Grade 3/4 toxicities included fatigue and reversible myelosuppression.

Conclusions:

  • Tipifarnib exhibits activity in heavily pretreated lymphoma, particularly HL/T types.
  • The drug showed limited activity in follicular non-Hodgkin lymphoma.
  • Further investigation of tipifarnib, potentially in combination therapy, is justified given its safety and mechanism.

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