دورية أكاديمية
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.
| العنوان: | 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. |
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| المؤلفون: | Rolland, Delphine, Ribrag, Vincent, Haioun, Corinne, Ghesquieres, Herve, Jardin, Fabrice, Bouabdallah, Reda, Franchi, Patricia, Briere, Josette, de Kerviler, Eric, Chassagne-Clement, Catherine, Raponi, Mitch, Houlgatte, Remi, Jais, Jean-Philippe, Thieblemont, Catherine |
| المساهمون: | Grenoble Institut des Neurosciences (GIN), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de recherche translationnelle, Direction de la recherche Gustave Roussy, Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Service d'hématologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Département Hématologie (FNCLCC), Centre Léon Bérard Lyon, Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Université de la Méditerranée - Aix-Marseille 2, Gvh et Gvl : Physiopathologie Chez l'Homme et Chez l'Animal, Incidence et Role Therapeutique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomo-pathologie Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de radiologie Saint-Louis, Département d'anatomopathologie, biopathologie, Div JANSSEN CILAG, SAS Res & Dev, Johnson & Johnson, Cardiopathies et mort subite ERL 3147, Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et pharmacologie cellulaires et moléculaires, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'informatique médicale et biostatistiques CHU Necker, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Necker - Enfants Malades AP-HP, Service d'onco-hématologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal Paris |
| المصدر: | ISSN: 0344-5704. |
| بيانات النشر: | HAL CCSD Springer Verlag |
| سنة النشر: | 2010 |
| المجموعة: | Inserm: HAL (Institut national de la santé et de la recherche médicale) |
| مصطلحات موضوعية: | MESH: A Kinase Anchor Proteins, MESH: Administration, Oral, MESH: Proto-Oncogene Proteins, MESH: Quinolones, MESH: Aged, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Survival Analysis, MESH: Treatment Outcome, MESH: Antineoplastic Agents, MESH: DNA-Binding Proteins, MESH: Drug Administration Schedule, MESH: Drug Resistance, Neoplasm, MESH: Humans, MESH: Female, MESH: Gene Expression Regulation, Neoplastic, MESH: Guanine Nucleotide Exchange Factors, MESH: Lymphoma, Mantle-Cell, MESH: Male, MESH: Neoplasm Recurrence, Local, MESH: Nuclear Proteins, MESH: Predictive Value of Tests, MESH: Prognosis, MESH: Prospective Studies, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | International audience ; 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/19960345; inserm-00527708; https://inserm.hal.science/inserm-00527708Test; PUBMED: 19960345 |
| DOI: | 10.1007/s00280-009-1185-4 |
| الإتاحة: | https://doi.org/10.1007/s00280-009-1185-4Test https://inserm.hal.science/inserm-00527708Test |
| رقم الانضمام: | edsbas.FAA86BF5 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1007/s00280-009-1185-4 |
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