Multi-institutional phase 2 study of the farnesyltransferase inhibitor tipifarnib (R115777) in patients with relapsed and refractory lymphomas

作者：Witzig Thomas E^*; Tang Hui; Micallef Ivana N M; Ansell Stephen M; Link Brian K; Inwards David J; Porrata Luis F; Johnston Patrick B; Colgan Joseph P; Markovic Svetomir N; Nowakowski Grzegorz S; Thompson Carrie A; Allmer Cristine; Maurer Matthew J; Gupta Mamta; Weiner George; Hohl Ray; Kurtin Paul J; Ding Husheng; Loegering David; Schneider Paula; Peterson Kevin; Habermann Thomas M; Kaufmann Scott H

来源：Blood, 2011, 118(18): 4882-4889.

DOI：10.1182/blood-2011-02-334904

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. (Blood. 2011;118(18):4882-4889)

• 出版日期2011-11-3