Multi-institutional Phase 2 Study of the Farnesyltransferase Inhibitor Tipifarnib (R115777) in Patients With Relapsed and Refractory Lymphomas

Blood. 2011 Nov 3;118(18):4882-9. doi: 10.1182/blood-2011-02-334904. Epub 2011 Jul 1.

Abstract

A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib was conducted in 93 adult patients with relapsed or refractory lymphoma. Patients received tipifarnib 300 mg twice daily on days 1-21 of each 28-day cycle. The median number of prior therapies was 5 (range, 1-17). For the aggressive B-cell, indolent B-cell, and T-cell and Hodgkin lymphoma (HL/T) groups, the response rates were 17% (7/42), 7% (1/15), and 31% (11/36), respectively. Of the 19 responders, 7 were diffuse large B-cell non-Hodgkin lymphoma (NHL), 7 T-cell NHL, 1 follicular grade 2, and 4 HL. The median response duration for the 19 responders was 7.2 months (mean, 15.8 months; range, 1.8-62), and 5 patients in the HL/T group are still receiving treatment at 29-64+ months. The grade 3/4 toxicities observed were fatigue and reversible myelosuppression. Correlative studies suggest that Bim and Bcl-2 should be examined as potential predictors of response in future studies. These results indicate that tipifarnib has activity in lymphoma, particularly in heavily pretreated HL/T types, with little activity in follicular NHL. In view of its excellent toxicity profile and novel mechanism of action, further studies in combination with other agents appear warranted. This trial is registered at www.clinicaltrials.gov as #NCT00082888.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Resistance, Neoplasm / drug effects
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / adverse effects
  • Enzyme Inhibitors / therapeutic use
  • Farnesyltranstransferase / antagonists & inhibitors
  • Female
  • Humans
  • Lymphoma / drug therapy*
  • Lymphoma / pathology
  • Male
  • Middle Aged
  • Quinolones / administration & dosage
  • Quinolones / adverse effects
  • Quinolones / therapeutic use*
  • Recurrence
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Quinolones
  • Farnesyltranstransferase
  • tipifarnib

Associated data

  • ClinicalTrials.gov/NCT00082888