Phase II trial and prediction of response of single agent tipifarnib in patients with relapsed/refractory mantle cell lymphoma: a Groupe d'Etude des Lymphomes de l'Adulte trial.

Abstract : PURPOSE: Farnesyltransferase (Ftase) was identified by gene-expression profiling and by preclinical evaluation in in vitro and in vivo mantle cell lymphoma (MCL) models as a rational therapeutic target in MCL, one of the most refractory B-cell lymphomas. We conducted a multicenter phase II study of a potent Ftase inhibitor, tipifarnib, in patients with relapsed or refractory MCL. METHODS: Tipifarnib was administered at 300 mg orally twice daily for the first 21 days of each 28-day cycle for 4 cycles, and in case of response for 6 cycles. Study endpoints were objective response at 4 and 6 cycles, progression free survival (PFS), overall survival, and toxicity. Prediction of response was retrospectively evaluated in the initial tumor biopsy by the RASGRP1/APTX gene expression ratio, and the AKAP13 expression level. RESULTS: Eleven patients (median age, 71 years) were enrolled. Patients received a median number of three prior therapies (range 1-11). Nine patients completed at least 3 cycles of tipifarnib. No grade III-IV hematological toxicities were recorded. One patient presented a complete response (CR) after 4 and a persistent CR at 6 cycles (ORR = 9%). Median PFS was 3 months (range 0.7-14.2). The RASGRP1/APTX gene expression ratio was higher in the responder (n = 1) while the AKAP13 expression was higher in the non-responders (n = 2). This corresponds to the expected result for predicting response to tipifarnib. CONCLUSION: Treatment with tipifarnib relapsed or refractory MCL is associated with low response rates. Limited gene expression studies suggest that response may be associated with molecular targets.
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Cancer Chemotherapy and Pharmacology, Springer Verlag, 2010, 65 (4), pp.781-90. 〈10.1007/s00280-009-1185-4〉
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Contributeur : Jean-Paul Issartel <>
Soumis le : mercredi 20 octobre 2010 - 10:08:16
Dernière modification le : jeudi 5 avril 2018 - 10:36:48

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Delphine Rolland, Vincent Ribrag, Corinne Haioun, Herve Ghesquieres, Fabrice Jardin, et al.. Phase II trial and prediction of response of single agent tipifarnib in patients with relapsed/refractory mantle cell lymphoma: a Groupe d'Etude des Lymphomes de l'Adulte trial.. Cancer Chemotherapy and Pharmacology, Springer Verlag, 2010, 65 (4), pp.781-90. 〈10.1007/s00280-009-1185-4〉. 〈inserm-00527708〉

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