title: A non-randomised dose-escalating phase II study of thalidomide for the treatment of patients with low-risk myelodysplastic syndromes: the Thal-SMD-2000 trial of the Groupe Français des Myélodysplasies.
abstract: Patients (n=47) with low-risk myelodysplastic syndrome were treated with thalidomide [200 mg/d, increased by 200 mg/d/4 weeks up to week 16]. Responses were evaluated according to the International Working Group criteria at week 16 for 39 patients who received at least 8 weeks of treatment. Twenty-three (59%) patients showed haematological improvement (HI): four major erythroid response (HI-EM), 15 minor erythroid response, six major neutrophil response, two major platelet response. Side effects caused 22/39 to stop thalidomide before week 16. Nine of 23 responders continued thalidomide after week 16 [19% of trial patients] with sustained response in eight of nine. Six reached week 56, including the four HI-EM patients [13% of trial patients]. Nineteen of 36 red blood cell transfusion-dependent patients (53%) showed erythroid response, but only four became transfusion-independent. Among the 23 responders, the median duration of response was 260 d (range 30-650). Responses were sustained in all patients except one, and were observed between week 4 and week 8 in 85% of patients, at doses ranging from 200 to 400 mg. Only two patients responded at 600 mg/d and none at 800 mg/d. No clinical characteristics of responding versus non-responding patients were identified. The erythroid response rate was identical in all cytogenetic subgroups, including 5q31.1 deletions. Pretreatment vascular endothelial growth factor levels were lower in responders compared with non-responders (P=0.004). Microvessel density (MVD) increased and apoptosis decreased in four of six and in all six responders studied respectively whereas MVD and apoptosis were unchanged in three non-responders.
authors.affiliation: Service d'Hématologie, Hôpital Cochin, Paris, France. bouscary@cochin.inserm.fr
authors.forename: Didier
authors.initials: D
authors.lastname: Bouscary
authors.forename: Laurence
authors.initials: L
authors.lastname: Legros
authors.forename: Micheline
authors.initials: M
authors.lastname: Tulliez
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Dubois
authors.forename: Béatrice
authors.initials: B
authors.lastname: Mahe
authors.forename: Odile
authors.initials: O
authors.lastname: Beyne-Rauzy
authors.forename: Marie C
authors.initials: MC
authors.lastname: Quarre
authors.forename: Dominique
authors.initials: D
authors.lastname: Vassilief
authors.forename: Bruno
authors.initials: B
authors.lastname: Varet
authors.forename: Achille
authors.initials: A
authors.lastname: Aouba
authors.forename: Martine
authors.initials: M
authors.lastname: Gardembas
authors.forename: Stéphane
authors.initials: S
authors.lastname: Giraudier
authors.forename: Agnès
authors.initials: A
authors.lastname: Guerci
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Fanny
authors.initials: F
authors.lastname: Gaillard
authors.forename: Anne
authors.initials: A
authors.lastname: Moreau
authors.forename: Marie C
authors.initials: MC
authors.lastname: Rousselet
authors.forename: Norbert
authors.initials: N
authors.lastname: Ifrah
authors.forename: Pierre
authors.initials: P
authors.lastname: Fenaux
authors.forename: François
authors.initials: F
authors.lastname: Dreyfus
mesh_terms: D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001854:Bone Marrow Cells / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D009389:Neovascularization, Pathologic; D012306:Risk; D018709:Statistics, Nonparametric; D013792:Thalidomide / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D020533:Angiogenesis Inhibitors; D015415:Biomarkers; D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide