13.08.2009

CLINICAL TRIALS AND OBSERVATIONS

A randomized phase 3 study of tipifarnib compared with best supportive care, including hydroxyurea, in the treatment of newly diagnosed acute myeloid leukemia in patients 70 years or older

Jean-Luc Harousseau¹, Giovanni Martinelli², Wieslaw W. Jedrzejczak³, Joseph M. Brandwein⁴, Dominique Bordessoule⁵, Tamas Masszi⁶, Gert J. Ossenkoppele⁷, Julia A. Alexeeva⁸, Gernot Beutel⁹, Johan Maertens¹⁰, Maria-Belen Vidriales¹¹, Hervé Dombret¹², Xavier Thomas¹³, Alan K. Burnett¹⁴, Tadeusz Robak¹⁵, Nuriet K. Khuageva¹⁶, Anatoly K. Golenkov¹⁷, Elena Tothova¹⁸, Lars Mollgard¹⁹, Youn C. Park²⁰, Annick Bessems²⁰, Peter De Porre²⁰, Angela J. Howes²⁰, and for the FIGHT-AML-301 Investigators
¹ University Hospital Hotel-Dieu, Nantes, France; ² University of Bologna, Bologna, Italy; ³ Medical University of Warsaw, Warsaw, Poland; ⁴ Princess Margaret Hospital, Toronto, ON; ⁵ Centre Hospitalier Universitaire Limoges, Limoges, France, ⁶ National Medical Center, Budapest, Hungary; ⁷ Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; ⁸ St Petersburg City Clinical Hospital, St Petersburg, Russia; ⁹ Medizinische Hochschule Hannover, Hannover, Germany; ¹⁰ UZ Gasthuisberg, Leuven, Belgium; ¹¹ Hospital Universitario de Salamanca, Salamanca, Spain; ¹² Hospital Saint-Louis, Paris, France; ¹³ Hospital Edouard Herriot, Lyon, France; ¹⁴ University Hospital of Wales, Cardiff, United Kingdom; ¹⁵ Medical University of Lodz and Memorial Copernicus Hospital, Lodz, Poland; ¹⁶ S. P. Botkin Moscow City Clinical Hospital, Moscow, Russia; ¹⁷ Moscow Regional Clinical Research Institute, Moscow, Russia; ¹⁸ Hospital University of PJS, Kosice, Slovak Republic; ¹⁹ Karolinska University Hospital, Stockholm, Sweden; and ²⁰ Ortho-Biotech Oncology R&D, a unit of Johnson & Johnson Pharmaceutical Research & Development LLC, Beerse, Belgium
This phase 3, multicenter, open-label study evaluated the efficacy and safety of tipifarnib compared with best supportive care (BSC), including hydroxyurea, as first-line therapy in elderly patients (70 years) with newly diagnosed, de novo, or secondary acute myeloid leukemia. A total of 457 patients were enrolled with 24% 80 years of age or older. Tipifarnib 600 mg orally twice a day was administered for the first 21 consecutive days, in 28-day cycles. The primary endpoint was overall survival. The median survival was 107 days for the tipifarnib arm and 109 days for the BSC arm. The hazard ratio (tipifarnib vs BSC) for overall survival was 1.02 (P value by stratified log-rank test, .843). The complete response rate for tipifarnib in this study (8%) was lower than that observed previously, but with a similar median duration of 8 months. The most frequent grade 3 or 4 adverse events were cytopenias in both arms, slightly more infections (39% vs 33%), and febrile neutropenia (16% vs 10%) seen in the tipifarnib arm. The results of this randomized study showed that tipifarnib treatment did not result in an increased survival compared with BSC, including hydroxyurea. This trial was registered at www.clinicaltrials.gov as #NCT00093990 [ClinicalTrials.gov] .