Prolonged survival with improved tolerability in higher‐risk myelodysplastic syndromes: azacitidine compared with low dose ara‐C

• Published in: British journal of haematology 2010-04, Vol.149 (2), p.244-249
• Main Authors: Fenaux, Pierre, Gattermann, Norbert, Seymour, John F., Hellström‐Lindberg, Eva, Mufti, Ghulam J., Duehrsen, Ulrich, Gore, Steven D., Ramos, Fernando, Beyne‐Rauzy, Odile, List, Alan, McKenzie, David, Backstrom, Jay, Beach, Charles L.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; azacitidine; Azacitidine - adverse effects; Azacitidine - therapeutic use; Biological and medical sciences; Cytarabine - adverse effects; Cytarabine - therapeutic use; Drug Administration Schedule; Erythrocyte Transfusion; Female; Hematologic and hematopoietic diseases; higher‐risk myelodysplastic syndromes; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; low‐dose cytarabine (ara‐C); Male; Medical sciences; Medicin och hälsovetenskap; Middle Aged; myelodysplastic syndromes; Myelodysplastic Syndromes - drug therapy; survival; Survival Analysis; Treatment Outcome
• ISSN: 0007-1048; 1365-2141; 1365-2141
• DOI: 10.1111/j.1365-2141.2010.08082.x

Summary In the phase III AZA‐001 trial, low‐dose cytarabine (LDara‐C), the most widely used low‐dose chemotherapy in patients with higher‐risk myelodysplastic syndrome (MDS) who are ineligible for intensive treatment, was found to be associated with poorer survival compared with azacitidine. This analysis further compared the efficacy and the toxicity of these two drug regimens. Before randomization, investigators preselected patients to receive a conventional care regimen, one of which was LDara‐C. Of 94 patients preselected to LDara‐C, 45 were randomized to azacitidine and 49 to LDara‐C. Azacitidine patients had significantly more and longer haematologicalal responses and increased red blood cell transfusion independence. Azacitidine prolonged overall survival versus LDara‐C in patients with poor cytogenetic risk, presence of −7/del(7q), and French‐American‐British subtypes refractory anaemia with excess blasts (RAEB) and RAEB in transformation. When analyzed per patient year of drug exposure, azacitidine treatment was associated with fewer grade 3–4 cytopenias and shorter hospitalisation time than LDara‐C in these higher‐risk MDS patients.