A phase II, randomized, blinded study of the farnesyltransferase inhibitor tipifarnib combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy

Breast Cancer Res Treat. 2008 Jul;110(2):327-35. doi: 10.1007/s10549-007-9726-1. Epub 2007 Sep 13.

Abstract

Background: This study assessed the clinical efficacy of the farnesyltransferase inhibitor, tipifarnib, combined with letrozole in patients with advanced breast cancer and disease progression following antiestrogen therapy.

Patients and methods: Postmenopausal women with estrogen-receptor-positive advanced breast cancer that had progressed after tamoxifen were given 2.5 mg letrozole once daily and were randomly assigned (2:1) to tipifarnib 300 mg (TL) or placebo (L) twice daily for 21 consecutive days in 28-day cycles. The primary endpoint was objective response rate.

Results: Of 120 patients treated with TL (n = 80) or L (n = 40), 113 were evaluable for response. Objective response rate was 30% (95% CI; 20-41%) for TL and 38% (95% CI; 23-55%) for L. There was no significant difference in response duration, time to disease progression or survival. Clinical benefit rates were 49% (TL) and 62% (L). Tipifarnib was generally well tolerated; a higher incidence of drug-related asymptomatic grade 3/4 neutropenia was observed for TL (18%) than for L (0%). Tipifarnib population pharmacokinetics were similar to previous studies, with no significant difference in trough letrozole concentrations between the TL and L groups.

Conclusions: Adding tipifarnib to letrozole did not improve objective response rate in this population of patients with advanced breast cancer.

Trial registration: ClinicalTrials.gov NCT00050141.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Double-Blind Method
  • Estrogen Receptor Modulators / therapeutic use*
  • Farnesyltranstransferase / antagonists & inhibitors*
  • Female
  • Humans
  • Letrozole
  • Middle Aged
  • Nitriles / administration & dosage*
  • Quinolones / administration & dosage*
  • Time Factors
  • Treatment Outcome
  • Triazoles / administration & dosage*

Substances

  • Estrogen Receptor Modulators
  • Nitriles
  • Quinolones
  • Triazoles
  • Letrozole
  • Farnesyltranstransferase
  • tipifarnib

Associated data

  • ClinicalTrials.gov/NCT00050141