@article{eba35e9b144742a48550f34f6e210849,
title = "On the use of lonafarnib in myelodysplastic syndrome and chronic myelomonocytic leukemia",
abstract = "Lonafarnib is an orally bio-available farnesyltransferase inhibitor that prevents farnesylation of specific target proteins including Ras. In a multicenter study, 67 patients with advanced myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) were treated with a continuous oral dose of 200-300mg of lonafarnib and were evaluated for hematologic, pathologic and pharmacodynamic response. The median age of patients was 70 years (range 44-86). There were 32 patients with MDS (RAEB-20 and RAEB-t-12) and 35 with CMML. Overall 16 (24%) of the patients responded with two patients achieving a complete remission and one a partial response. Responses were seen in 6/32 and 10/35 patients with MDS and CMML, respectively. Of the 19 patients who were platelet transfusion-dependent prior to treatment, 5 (26%) became transfusion-free for a median duration of 185 days. A decrease in the farnesylation of the HDJ-2 protein measured in patient-derived cells was observed in the majority of patients during treatment with lonafarnib, but no clear correlation between changes in farnesylation and clinical effect could be made. Gastrointestinal toxicity was significant with 19% of patients discontinuing therapy due to diarrhea, nausea and/or anorexia. Lonafarnib has demonstrable activity in patients with advanced MDS and CMML.",
author = "Feldman, {E. J.} and J. Cortes and DeAngelo, {D. J.} and T. Holyoake and B. Simonsson and O'Brien, {S. G.} and J. Reiffers and Turner, {A. R.} and Roboz, {G. J.} and Lipton, {J. H.} and F. Maloisel and P. Colombat and G. Martinelli and Nielsen, {J. L.} and S. Petersdorf and F. Guilhot and J. Barker and P. Kirschmeier and E. Frank and P. Statkevich and Y. Zhu and S. Loechner and A. List",
note = "Funding Information: 1Division of Hematology and Medical Oncology, Weill-Cornell Medical College, New York, NY, USA; 2Department of Leukemia, MD Anderson Cancer Center, Houston, TX, USA; 3Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA, USA; 4Division of Cancer and Molecular Pathology, Glasgow Royal Infirmary, Glasgow, Scotland; 5Department of Hematology, University Hospital, Uppsala, Sweden; 6Department of Hematology, Newcastle University, Newcastle upon Tyne, UK; 7Institut Bergonie and Universite Victor Segalen, Bordeaux, France; 8Division of Medical Oncology, Cross Cancer Institute, Edmonton, Canada; 9Division of Medical Oncology and Hematology and Oncology, Princess Margaret Hospital, Ontario, Canada; 10Department of Hematologie-Oncologie, Hopitaux Universitaires de Strasbourg, Strasbourg, France; 11Department of Hematology, CHU Tours, France; 12Department of Hematology/Oncology, Universita{\textquoteright} di Bologna, Bologna, Italy; 13Department of Hematology, University Hospital, Arhus, Denmark; 14Division of Medical Oncology, Seattle Cancer Care Alliance, Seattle, WA, USA; 15Department of Oncology-Haematology and Cell therapeutics, CIC INSERM 802 C.H.U. de Poitiers, Poitiers, France; 16Department of Hematology, University of Minnesota, Minneapolis, MN, USA; 17Schering-Plough Research Institute, Kenilworth, NJ, USA and 18Malignant Hematology Division, H. Lee Moffit Cancer Center and Research Institute, Tampa, FL, USA",
year = "2008",
doi = "10.1038/leu.2008.156",
language = "English (US)",
volume = "22",
pages = "1707--1711",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "9",
}