The Combination of Fludarabine, Cytarabine and Etoposide Is an Active and Well-Tolerated Regimen in Relapsed/Refractory Acute Myeloid Leukemia

Abstract

We retrospectively reviewed the outcome of 20 consecutive subjects with refractory/relapsed acute myeloid leukemia (AML; 9 refractory and 11 relapsed) treated at our institution with a fludarabine, cytarabine and etoposide (FCE) salvage regimen. Of 20 patients with refractory/relapsed AML, 15 (75%) achieved complete remission (CR)/CR with incomplete peripheral blood count recovery (CRi), including 14 CR and 1 CRi. The 4- and 8-week treatment-related mortality (TRM) for all patients during reinduction was 0 and 5%, respectively. Eight of 15 patients (53%) who successfully achieved CR were able to undergo allogeneic hematopoietic stem cell transplantation with a 0% non-relapse mortality rate. FCE is a new, well-tolerated, anthracycline-free regimen, which has a promising activity in relapsed/refractory AML and is associated with low TRM in this high-risk population.

Etoposide Combined with FLAG Salvage Therapy Is Effective in Multiple Relapsed/Refractory Acute Myeloid leukemia

“…Despite the impaired performance status among FLAG-Eto-treated patients at baseline we did not observe a significant increase in the frequency of grade 3/4 toxicities compared to the toxicity profile of our previously published FLAG-Ida regime [9]. To our knowledge, there is only one published study on the efficacy of the FLAG-Eto protocol in 20 patients, of whom only 15% received one prior salvage therapy and 5% previously underwent allogeneic stem cell transplantation [17]. In this patient cohort higher anti-leukemic activity with CR/CRi rates of 75% and a 1-year overall survival of 71% has been achieved with a more beneficial toxicity profile.…”

FLAG and Etoposide as Salvage Treatment in Acute Myeloid Leukemia

“…Minimal residual disease was also not reported to assess the depth of response, especially before allo-HSCT. The mortality rate appears to have been higher than in the experience of Aldoss et al [3], with infections being the main driver, but it is not possible to draw firm conclusions.…”

“…In Hanoun et al, etoposide was added to FLAG at a dose of 150 mg/m 2 /day for 3 days. Notably, in a previously published paper by Aldoss et al [3] etoposide was administered at 100 mg/m 2 /day for 5 days. The study by Hanoun et al includes older patients (up to the age of 71 years), 30% of whom received FLAG and idarubicin (FLAG-IDA) previously.…”

Facts about FCE (Fludarabine, Cytarabine, Etoposide) in Acute Myeloid Leukemia

“…Similar to that previously reported, age and duration of prior remission were important predictive factors of response to salvage therapy. Collectively, these outcomes are not substantially different to the results described by Aldoss et al [3]. …”

“…In light of these issues, how much enthusiasm should the findings of Aldoss et al [3] generate? In the manuscript accompanying this editorial, the authors report the clinical outcomes of younger patients with relapsed/refractory AML following treatment with FCE (fludarabine, cytarabine, and etoposide) as salvage therapy.…”