Clofarabine in the Treatment of Elderly Patients with Acute Myeloid Leukemia

Abstract

Background: Elderly patients with acute myeloid leukemia (AML) have a poor outcome because of comorbidities, poor tolerance to intensive chemotherapy and inherently more resistant disease. Clofarabine is a second generation nucleoside analogue which has shown promising activity in elderly patients with AML. This study was conducted to review the outcome of treatment with clofarabine in a group of such patients. Methods: The records of 5 elderly patients who were diagnosed to have AML and treated with clofarabine over a 12 month period were reviewed retrospectively. Results: There were 2 female and 3 male patients with a median age of 68 years (range 65-82). At the time of treatment, 2 patients had newly diagnosed AML not considered suitable for intensive therapy, while 3 patients had partial or no response to conventional chemotherapy. The overall response rate was 100%, all patients achieving a complete remission. Induction and consolidation were well tolerated. All patients developed neutropenia with a median duration of 20 days (range 17-42). One patient developed hand and foot syndrome and a generalized rash but recovered. There was no mortality and all patients remained in remission after a median follow-up of 5.2 months (Range 3-10). Conclusion: Clofarabine (alone or in combination) is active in elderly AML patients with an acceptable safety profile and should be considered a potential option in this group.

Versatile synthesis and biological evaluation of novel 3’-fluorinated purine nucleosides

“…Anticancer drugs cladribine and clofarabine [ 55 – 57 ] are purine nucleoside derivatives having a chlorine atom at position 2 of the purine moiety. With this in mind, we designed and synthesized 2-chloropurine nucleosides 16 – 20 ( Fig.…”

“…As mentioned above, chloropurine [ 55 – 57 ] and deaminopurine [ 42 – 43 ] nucleosides have exhibited potent biological activities. We synthesized 2-amino-6-chloropurine 3’-deoxy-3’-fluororiboside 22 and 2-aminopurine-3’-deoxy-3’-fluororiboside 21 to explore the SAR of 3’-fluorine-substituted purine nucleoside derivatives ( Scheme 5 ).…”