A randomized study of 2 dose levels of intravenous clofarabine in the treatment of patients with higher‐risk myelodysplastic syndrome

• Published in: Cancer Vol. 118; no. 3; pp. 722 - 728
• Main Authors: Faderl, Stefan, Garcia‐Manero, Guillermo, Jabbour, Elias, Ravandi, Farhad, Borthakur, Gautam, Estrov, Zeev, Gandhi, Varsha, Byrd, Anna L., Kwari, Monica, Cortes, Jorge, Kantarjian, Hagop M.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.02.2012; Wiley-Blackwell
• Subjects: Adenine Nucleotides - administration & dosage; Adult; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Arabinonucleosides - administration & dosage; Biological and medical sciences; clofarabine; Cohort Studies; DNA methyltransferase inhibitors; Drug Administration Schedule; Female; Hematologic and hematopoietic diseases; Humans; Injections, Intravenous; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; myelodysplastic syndrome; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - mortality; nucleoside analogs; Remission Induction; Risk Factors; Survival Rate; Treatment Outcome; Tumors; Antineoplastic agent; Human; Intravenous administration; DNA methyltransferase inhibitors; Malignant hemopathy; Clofarabine; Myelodysplastic syndrome; Randomization; Cancerology; Treatment; nucleoside analogs; Antimetabolic; Risk factor; Nucleoside analog; Inhibitor; Dose; Cancer
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.26327

BACKGROUND: Clofarabine is a nucleoside analog with activity in myeloid malignancies. Experience in myelodysplastic syndrome (MDS) is limited. METHODS: The goal of this study was to evaluate the activity and safety of 2 different doses (15 mg/m2 vs 30 mg/m2 daily × 5 days) of intravenous clofarabine in patients with higher‐risk MDS. Fifty‐eight patients with a median age of 68 years (range, 25‐89) including 15 patients (28%) with secondary MDS and 35 patients (60%) who received prior DNA methyltransferase (DNMT) inhibitors were adaptively randomized between the 2 dose cohorts. RESULTS: The overall response rate (ORR; based on a modification of International Working Group criteria) was 36% including 26% with complete remission (CR) (ORR, 41% at 15 mg/m2 and 29% at 30 mg/m2). Responses were lower in patients who failed DNMT inhibitors (ORR, 17%; CR rate, 14%). The 8‐week mortality rate was 19%. Median survival was 7.4 months for all patients, 13.4 months for responders, and 21.7 months for complete responders. Some adverse events, particularly hepatic and renal, were more severe (grade >2) in patients randomized to 30 mg/m2 of clofarabine. Myelosuppression and infectious complications were frequent. CONCLUSIONS: Both the lower and higher doses of clofarabine have comparable clinical activity, but the lower dose appeared less toxic. If these results are confirmed, lower doses of clofarabine, possibly in alternative schedules, should be pursued. Cancer 2012;. © 2011 American Cancer Society. Intravenous clofarabine was used at 2 different dose levels in patients with higher‐risk myelodysplastic syndrome. Responses were comparable, but the lower dose level was less toxic. Activity has been noted in patients with and without prior exposure to DNA methyltransferase inhibitors.