title: Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas.
abstract: A phase 2 study of the oral farnesyltransferase inhibitor tipifarnib was conducted in 93 adult patients with relapsed or refractory lymphoma. Patients received tipifarnib 300 mg twice daily on days 1-21 of each 28-day cycle. The median number of prior therapies was 5 (range, 1-17). For the aggressive B-cell, indolent B-cell, and T-cell and Hodgkin lymphoma (HL/T) groups, the response rates were 17% (7/42), 7% (1/15), and 31% (11/36), respectively. Of the 19 responders, 7 were diffuse large B-cell non-Hodgkin lymphoma (NHL), 7 T-cell NHL, 1 follicular grade 2, and 4 HL. The median response duration for the 19 responders was 7.2 months (mean, 15.8 months; range, 1.8-62), and 5 patients in the HL/T group are still receiving treatment at 29-64+ months. The grade 3/4 toxicities observed were fatigue and reversible myelosuppression. Correlative studies suggest that Bim and Bcl-2 should be examined as potential predictors of response in future studies. These results indicate that tipifarnib has activity in lymphoma, particularly in heavily pretreated HL/T types, with little activity in follicular NHL. In view of its excellent toxicity profile and novel mechanism of action, further studies in combination with other agents appear warranted. This trial is registered at www.clinicaltrials.gov as #NCT00082888.
authors: Division of Hematology, Department of Medicine, Mayo Clinic College of Medicine and Mayo Foundation, Rochester, MN, USA. witzig@mayo.edu
authors: Thomas E
authors: TE
authors: Witzig
authors: Hui
authors: H
authors: Tang
authors: Ivana N M
authors: IN
authors: Micallef
authors: Stephen M
authors: SM
authors: Ansell
authors: Brian K
authors: BK
authors: Link
authors: David J
authors: DJ
authors: Inwards
authors: Luis F
authors: LF
authors: Porrata
authors: Patrick B
authors: PB
authors: Johnston
authors: Joseph P
authors: JP
authors: Colgan
authors: Svetomir N
authors: SN
authors: Markovic
authors: Grzegorz S
authors: GS
authors: Nowakowski
authors: Carrie A
authors: CA
authors: Thompson
authors: Cristine
authors: C
authors: Allmer
authors: Matthew J
authors: MJ
authors: Maurer
authors: Mamta
authors: M
authors: Gupta
authors: George
authors: G
authors: Weiner
authors: Ray
authors: R
authors: Hohl
authors: Paul J
authors: PJ
authors: Kurtin
authors: Husheng
authors: H
authors: Ding
authors: David
authors: D
authors: Loegering
authors: Paula
authors: P
authors: Schneider
authors: Kevin
authors: K
authors: Peterson
authors: Thomas M
authors: TM
authors: Habermann
authors: Scott H
authors: SH
authors: Kaufmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D051231:Farnesyltranstransferase / Q000037:antagonists & inhibitors; D005260:Female; D006801:Humans; D008223:Lymphoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D015363:Quinolones; D051231:Farnesyltranstransferase; C402769:tipifarnib