title: A phase II, multicenter, open-label study of obatoclax mesylate in patients with previously untreated myelodysplastic syndromes with anemia or thrombocytopenia.
abstract: BACKGROUND
  Obatoclax mesylate is a small-molecule Bcl-2 homology domain-3 mimetic that neutralizes antiapoptotic Bcl-2-related proteins. We evaluated obatoclax in untreated MDS patients with anemia/thrombocytopenia.
  
  
  METHODS
  Twenty-four patients with a bone marrow blast count of ≤ 10% and anemia (hemoglobin level < 10 g/dL) or thrombocytopenia (platelet count < 50 × 10(9)/L) were eligible to receive intravenous obatoclax 60 mg over 24 hours every 2 weeks.
  
  
  RESULTS
  Response rate was 8% (2 patients; hematologic improvement). Disease stabilization/response was maintained ≥ 12 weeks in 50% (12 patients). Because the response rate was below a predetermined threshold, the study was terminated. Adverse events (any grade) included euphoric mood (63%; 15 patients), nausea (38%; 9 patients), and diarrhea (25%; 6 patients); Grade 3/4 adverse events included anemia (21%; 5 patients), thrombocytopenia (13%; 3 patients), and pneumonia (13%; 3 patients).
  
  
  CONCLUSIONS
  Obatoclax 60 mg every 2 weeks was feasible, but had limited first-line activity in MDS.
authors: Department of Hematology and Oncology, Emory University School of Medicine, Atlanta, GA. Electronic address: MARELLA@emory.edu.
authors: Martha L
authors: ML
authors: Arellano
authors: Department of Leukemia, Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX.
authors: Gautam
authors: G
authors: Borthakur
authors: Department of Clinical Development, Gemin X Pharmaceuticals, Malvern, PA.
authors: Mark
authors: M
authors: Berger
authors: Department of Medical Affairs, Powered 4 Significance LLC, Annandale, NJ.
authors: Jill
authors: J
authors: Luer
authors: Division of Hematology/Oncology, Columbia University Medical Center, New York, NY.
authors: Azra
authors: A
authors: Raza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000209:etiology*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007211:Indoles; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000175:diagnosis / Q000188:drug therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000209:etiology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; C520962:obatoclax
keywords: BH3 mimetic; Efficacy; Elderly; Myelosuppression; Safety