Oral Clofarabine in the Treatment of Patients With Higher-Risk Myelodysplastic Syndrome

• Published in: Journal of clinical oncology Vol. 28; no. 16; pp. 2755 - 2760
• Main Authors: FADERL, Stefan, GARCIA-MANERO, Guillermo, KWARI, Monica, KANTARJIAN, Hagop M, ESTROV, Zeev, RAVANDI, Farhad, BORTHAKUR, Gautam, CORTES, Jorge E, O'BRIEN, Susan, GANDHI, Varsha, PLUNKETT, William, BYRD, Anna
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01.06.2010
• Subjects: Adenine Nucleotides - administration & dosage; Adenine Nucleotides - adverse effects; Administration, Oral; Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Arabinonucleosides - administration & dosage; Arabinonucleosides - adverse effects; Biological and medical sciences; Clofarabine; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hematologic and hematopoietic diseases; Humans; Kaplan-Meier Estimate; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Maximum Tolerated Dose; Medical sciences; Middle Aged; Myelodysplastic Syndromes - diagnosis; Myelodysplastic Syndromes - drug therapy; Myelodysplastic Syndromes - mortality; ORIGINAL REPORTS; Probability; Prognosis; Prospective Studies; Risk Assessment; Survival Analysis; Time Factors; Treatment Outcome; Tumors; Antineoplastic agent; Human; Cancerology; Treatment; Antimetabolic; Risk factor; Nucleoside analog; Malignant hemopathy; Clofarabine; Myelodysplastic syndrome; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2009.26.3509

Efficacy and toxicity profile of orally administered clofarabine were evaluated in patients with higher-risk myelodysplastic syndrome (MDS). Thirty-two patients were treated, of whom 22 had intermediate-2 or high-risk disease (International Prognostic Scoring System). Median age was 70 years (range, 53 to 86), nine patients had secondary MDS, and 20 patients experienced prior therapy failure with hypomethylating agents. Three doses of clofarabine were evaluated: 40 mg/m(2), 30 mg/m(2), and 20 mg/m(2) daily for 5 days. Courses were repeated every 4 to 8 weeks. Eight patients (25%) achieved complete remission (CR), three had (9%) hematologic improvement (HI), and three had (9%) clinical benefit (CB; overall response rate, 43%). Responses in patients who experience treatment failure with hypomethylating agents included CR in two (10%), HI in two (10%), and CB in two patients (10%). No patients died within 6 weeks of induction. Renal failure occurred in four patients in the context of myelosuppression-associated infectious complications. Common adverse events were gastrointestinal and hepatic. Myelosuppression was common, but prolonged myelosuppression (> 42 days) was rare. The toxicity profile was better with lower doses of clofarabine, whereas response rates did not differ significantly. Oral clofarabine has achieved a response rate of 43% in patients with higher-risk MDS. The optimal dose and schedule and the appropriate patient population for such therapy remain to be further defined.