Clofarabine in the treatment of poor risk acute myeloid leukaemia

Abstract

Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24-76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17-120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients.

The role of clofarabine in acute myeloid leukemia

“…The role of IV single-agent clofarabine was also studied in a smaller cohort of patients with AML with poor risk features, deemed unsuitable for standard therapy [26]. Twenty-two patients were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment.…”

Clofarabine in the Treatment of Elderly Patients with Acute Myeloid Leukemia

“…Clofarabine, a second generation nucleoside analog, has shown activity in patients with relapsed or refractory acute myeloid leukemia in younger and older patients as a single agent and in combination with high dose ARA-C. Krawczyk et al, 2010;Tse et al, 2011). A recent review of clofarabine in the elderly patients with AML revealed that clofarabine may be appropriate in a subset of patients with poor performance status and cardiovascular disease, not fit for intensive chemotherapy (Tran and Yang, 2012).…”

“…Clofarabine has also shown activity in combination with high dose ARA-C in relapsed or refractory younger and older patients with AML (Tse et al, 2011). Most of the studies published previously come from limited centers from the US or Europe and there is a lack of experience with this drug in the community setting (Krawczyk et al, 2010). Here we describe our experience in the elderly AML patients treated with clofarabine.…”

Acute leukaemia: making sense of a complex blood cancer

“…Kassim et al (2005). Additionally, Clofarabine should be considered for elderly patients as they are often not considered suitable transplant candidates and they often present with unfavorable risk disease (Krawczyk et al, 2010).…”