title: Phase I trial of low-dose oral Clofarabine in myelodysplastic syndromes patients who have failed frontline therapy.
abstract: We investigated protracted low-dose oral Clofarabine for the treatment of myelodysplastic syndromes (MDS). Adults with an International Prognostic Scoring System (IPSS) score of INT-1 or higher who had failed first line therapy were eligible. INT-1 patients had to be transfusion-dependent. We started with oral Clofarabine at 5mg (fixed dose) daily for 10 consecutive days on a 28-day cycle. Toxicity prompted a modification to 1mg PO daily for 10 days and then 1mg PO daily for 7 days. Patients received treatment indefinitely until loss of response or unacceptable toxicity. Nine patients (5 women) were enrolled and evaluable (median age 65 years; range 55-81). A 10-day regimen of oral Clofarabine at 5mg/day induced Grade IV pancytopenia. A dose of 1 mg/day for 7/28 days was very well tolerated without significant toxicity. Three patients had responses (2 with responses lasting up to 21 and 51 cycles) defined as stable disease in spite of no significant change on bone marrow evaluation. Low-dose oral Clofarabine (1mg daily for 7/28 days) proved both effective and safe for patients with MDS who had failed prior therapy. This patient population is particularly sensitive to more protracted Clofarabine treatment schedules.
authors.affiliation: Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, United States.
authors.forename: Venkatesh K
authors.initials: VK
authors.lastname: Rudrapatna
authors.affiliation: Hematology/Oncology, St. Joseph Mercy Hospital, Ann Arbor, MI, United States.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Morley
authors.affiliation: Division of Epidemiology, University of Utah-Huntsman Cancer Institute, Salt Lake City, UT, United States.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Boucher
authors.affiliation: Hematology/Oncology, St. Alphonsus Cancer Care Center, Nampa, ID, United States.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Pierson
authors.affiliation: Hematology/Oncology, Snake River Oncology of Eastern Idaho, Idaho Falls, ID, United States.
authors.forename: Christian T
authors.initials: CT
authors.lastname: Shull
authors.affiliation: Division of Hematology and Hematologic Malignancies, University of Utah-Huntsman Cancer Institute, Salt Lake City,, UT, United States.
authors.forename: James P
authors.initials: JP
authors.lastname: Kushner
authors.affiliation: Division of Hematology and Hematologic Malignancies, University of Utah-Huntsman Cancer Institute, Salt Lake City,, UT, United States. Electronic address: paul.shami@utah.edu.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Shami
mesh_terms: D000227:Adenine Nucleotides / Q000008:administration & dosage* / Q000009:adverse effects; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001087:Arabinonucleosides / Q000008:administration & dosage* / Q000009:adverse effects; D000077866:Clofarabine; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy*; D020360:Neoadjuvant Therapy; D017211:Treatment Failure
chemical_list: D000227:Adenine Nucleotides; D000970:Antineoplastic Agents; D001087:Arabinonucleosides; D000077866:Clofarabine
keywords: Clofarabine; Myelodysplasia; Myelodysplastic syndrome