A phase II, randomized, blinded study of the farnesyltransferase inhibitor tipifarnib combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy.
Johnston, S Semiglazov, Vladimir F Manikhas, George M Spaeth, Dominique Romieu, Gilles Dodwell, David J Neven, Patrick Bessems, Annick Park, Youn C
Johnston, S
Semiglazov, Vladimir F
Manikhas, George M
Spaeth, Dominique
Romieu, Gilles
Dodwell, David J
Neven, Patrick
Bessems, Annick
Park, Youn C
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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.
Description
Date
2008-07
Publisher
Collections
Keywords
Farnesyltransferase Inhibitor
Tipifarnib
Breast Cancer
Clinical Trial
Letrozole
Tipifarnib
Breast Cancer
Clinical Trial
Letrozole
Type
Article
Citation
A phase II, randomized, blinded study of the farnesyltransferase inhibitor tipifarnib combined with letrozole in the treatment of advanced breast cancer after antiestrogen therapy. 2008, 110 (2):327-35 Breast Cancer Res. Treat.