The value of oral cytarabine ocfosfate and etoposide in the treatment of refractory and elderly AML patients

Abstract

Twenty-one acute myeloid leukemia (AML) patients were enrolled and received oral induction therapy with cytarabine ocfosfate (SPAC) and etoposide (EP). The median age was 69 years (range: 33-86). There were 11 patients with de novo AML and 10 AML cases that had evolved from myelodysplastic syndromes. Seventeen patients had abnormal karyotypes including eight complex abnormalities, various complications, and 7 of 21 had a poor performance status (PS) with Eastern Cooperative Oncology Group (ECOG) scores of 3-4. All patients completed induction therapy without severe adverse events. Seven achieved complete remission (CR), and two achieved partial remission (PR). Uni- and multivariate analyses demonstrated a positive and significant correlation between the results of therapy (CR +/- PR) and overall survival. The plasma concentrations of cytosine arabinoside (ara-C) in some cases were higher than those previously reported, indicating the accumulation of ara-C with increasing numbers of days of SPAC administration. We conclude that this therapy is well tolerated and useful for refractory and elderly AML patients.

Efficacy of Oral Cytarabine Ocfosfate and Etoposide in the Treatment of Elderly Patients with Higher-Risk Myelodysplastic Syndromes Compared to That in Elderly Acute Myeloid Leukemia Patients

“…1 and 10) with longer-lasting nadirs responded well to this treatment. Although ara-C levels were not measured in these MDS patients, a previous report states that the plasma concentration of ara-C is comparatively higher in AML patients with SPAC and EP combination therapy [8]. It is possible that the higher ara-C concentrations cause more marked myelosuppression and induce a reduction of leukemic blasts.…”

“…SPAC, at a dose of 300 mg/day, provides a pharmacokinetic profile similar to that of low-dose intravenous administration of ara-C (20 mg/m 2 /day) [8,21]. Several clinical trials using SPAC to treat AML and MDS [22,23,24] have shown the effectiveness of this regimen at doses of 100-400 mg/day for more than 14 days.…”

“…Between 1997 and 2008, we enrolled 4 RAEB and 6 FAB-defined RAEB-T patients (5 males and 5 females) and 12 patients with AML (8 males and 4 females). Seven of these AML cases were reported previously [8]. …”

“…Low-dose ara-C has been used for some time for the treatment of MDS and provides effective antileukemic therapy [7]. We have already shown that using SPAC in combination with oral etoposide (EP) in refractory and elderly AML patients yields a favorable outcome [8]. Therefore, the present study used the same regimen to compare the response of elderly higher-risk MDS patients and elderly AML patients to demonstrate the efficacy and safety profile of these agents.…”

Improving nucleoside analogs via lipid conjugation: Is fatter any better?

“…Off-target toxicities limited dose-escalation in these studies as well [45, 46]. A small combination study of orally administered cytarabine ocfosfate and etoposide showed higher induction of complete remission in treating patients with hematological malignancies compared to previous single agent or combination trials [47], and two recent follow-up studies supported these findings [48, 49]. …”