A Multicenter Phase 2 Study of the Farnesyltransferase Inhibitor Tipifarnib in Intermediate- To High-Risk Myelodysplastic Syndrome

Blood. 2007 May 15;109(10):4158-63. doi: 10.1182/blood-2006-07-035725. Epub 2007 Jan 30.

Abstract

This multicenter phase 2 study evaluated the use of tipifarnib (R115777) in patients with poor-risk myelodysplastic syndrome (MDS; French-American-British classification). Patients (n = 82) received tipifarnib 300 mg orally twice daily for the first 21 days of each 28-day cycle. Twenty-six patients (32%) responded to tipifarnib: 12 (15%) complete responses (CRs) and 14 (17%) hematologic improvements; 37 patients (45%) had stable disease (modified International Working Group criteria, 2006). Among the 12 CRs, the median response duration was 11.5 months (range, 2.0-21.9 months), the median time to progression was 12.4 months (range, 3.9-23.8 months), and 7 were still alive at time of analysis (all > 3 years). Median overall survival was 11.7 months (95% CI, 9.4-15.0). Grade 3-4 neutropenia (18%) and thrombocytopenia (32%) were the most common treatment-related adverse events; severe nonhematologic adverse events were rarely reported. In this study, durable responses and acceptable side effects were observed. Tipifarnib is an active agent for the treatment of patients with intermediate- to high-risk MDS.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Blood Transfusion
  • Farnesyltranstransferase / antagonists & inhibitors*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myelodysplastic Syndromes / drug therapy*
  • Myelodysplastic Syndromes / mortality
  • Myelodysplastic Syndromes / pathology
  • Quinolones / administration & dosage
  • Quinolones / adverse effects
  • Quinolones / therapeutic use*
  • Risk
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Quinolones
  • Farnesyltranstransferase
  • tipifarnib