Bortezomib combined with low-dose cytarabine in Intermediate-2 and high risk myelodysplastic syndromes. A phase I/II Study by the GFM |
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Authors: | Natarajan-Amé Shanti,Park Sophie,Ades Lionel,Vey Norbert,Guerci-Bresler Agnès,Cahn Jean-Yves,Etienne Gabriel,Bordessoule Dominique,Ravoet Christophe,Legros Laurence,Cheze Stephane,Stamatoullas Aspasia,Berger Elisabeth,Schmidt Aline,Charbonnier Aude,Chaury Marie-Pierre,Braun Thorsten,Fenaux Pierre,Dreyfus Francois Groupe Francophone des Myélodysplasies |
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Affiliation: | Hopitaux Universitaires de Strasbourg, Strasbourg, France. shanti.ame@chru-strasbourg.fr |
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Abstract: | Marrow cells from patients with higher-risk myelodysplastic syndrome (MDS) exhibit constitutive nuclear factor (NF)-κB activation. The proteasome inhibitor, bortezomib, has limited efficacy as a single agent in acute myeloid leukaemia. Its activity on leukaemic cell lines is potentiated by chemotherapy. We treated 43 higher-risk MDS patients with bortezomib (1·5 mg/m(2) , days 1, 4, 8 and 11) and low dose cytarabine arabinoside (LDAC; 10 mg/m(2) , then 20 mg/m(2) from days 1-14), every 28 d for four cycles. Median follow-up was 29·7 months. Responses were seen in 12 of the 43 patients (28%), including complete response (CR, n = 1), marrow-CR (n = 3), partial response (PR, n = 5) and haematological improvement (HI, n = 3). Responses were seen in 12 (36%) of the 33 previously untreated patients (11% CR, 13% PR, 2·5% HI), compared to none in the 12 previously treated patients (P < 0·01). Responders had better overall survival (median 18·2 vs. 10 months). One CR and 3 marrow-CRs were seen in patients with complex karyotypes. Main toxicity was haematological, responsible for infection in six patients and bleeding in 3. Three patients with Grade 1-2 pre-treatment haematotoxicity developed Grade 3-4 toxicity. Neuropathy was seen in 12% of patients. The addition of bortezomib to LDAC in higher-risk MDS may improve results obtained with LDAC alone, especially in patients with unfavourable karyotypes. |
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Keywords: | bortezomib myelodysplastic syndromes higher‐risk MDS high risk MDS intermediate‐2 risk MDS |
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