title: A multicenter phase 2 study of the farnesyltransferase inhibitor tipifarnib in intermediate- to high-risk myelodysplastic syndrome.
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.
authors.affiliation: Hôpital Avicenne, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: Azra
authors.initials: A
authors.lastname: Raza
authors.forename: Ghulam J
authors.initials: GJ
authors.lastname: Mufti
authors.forename: Carlo
authors.initials: C
authors.lastname: Aul
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.forename: Larry
authors.initials: L
authors.lastname: Cripe
authors.forename: René
authors.initials: R
authors.lastname: Kerstens
authors.forename: Peter
authors.initials: P
authors.lastname: De Porre
authors.forename: Razelle
authors.initials: R
authors.lastname: Kurzrock
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001803:Blood Transfusion; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012306:Risk; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015363:Quinolones; D051231:Farnesyltranstransferase; C402769:tipifarnib