Abstract
Cytarabine (Ara-C) in consolidation therapy played important role in preventing relapses for AML patients achieved complete remission, but the optimum dose remains elusive. In this network meta-analysis, we compared benefit and safety of high-, intermediate- and low-dose Ara-C [HDAraC (>2 g/m2, ≤3 g/m2 twice daily), IDAraC (≥1 g/m2, ≤2 g/m2 twice daily) and LDAraC (<1 g/m2 twice day)] in consolidation, based on ten randomized phase III/IV trials from 1994 to 2016, which included 4008 adult AML patients. According to the results, HDAraC in a dosage of 3 g/m2 twice daily significantly improved disease-free survival (DFS) compared with IDAraC [hazard rate (HR) 0.87, 95% CrI 0.79–0.97) and LDAraC (HR 0.86, 95% CrI 0.78–0.95). Subgroup analysis further showed that the DFS advantage of HDAraC is focused on the patients with favorable cytogenetics, but not the other cytogenetics. Compared with LDAraC, HDAraC (HR 6.04, 95% CrI 1.67–21.49) and IDAraC (HR 3.80, 95% CrI 1.05–12.85) were associated with higher risk of grade 3–4 non-haematological toxicity. However, no significant difference between HDAraC and IDAraC was found. These findings suggest that Ara-C in a dosage of 3 g/m2 twice daily provides maximal anti-relapse effect.
Highlights
With an incidence of [3,4] every 100,000 people, acute myeloid leukemia (AML) is the most common acute leukemia in the world
As Cancer and Leukemia Study Group B (CALGB) 8525 trial revealed that high-dose cytarabine (HDAraC: 3 g/m2 twice daily over 3 days) regimen was superior to two low-dose cytarabine regimens (LDAraC: 0.4 g/m2 and 0.1 g/m2 over 5 days) for untreated AML patients, repetitive cycles of single-agent HDAraC was widely adopted as a standard post-remission chemotherapy[7]
In subgroup analysis stratified by cytogenetics (Fig. 4a and b), HDAraC in consolidation chemotherapy significantly benefited disease-free survival (DFS) for patients with favorable cytogenetic compared with IDAraC (HR 0.46, 95% credible intervals (CrIs) 0.35– 0.60) and LDAraC (HR 0.39, 95% CrI 0.26–0.59)
Summary
Open-labeled, randomized phase III/IV trials were included for this meta-analysis (Table 1), with a total of 4008 AML patients randomized to receive one of the three dose range of Ara-C in consolidation: high-dose Ara-C [HDAraC (>2 g/m2, ≤3 g/m2 twice daily)], intermediate-dose Ara-C [IDAraC (≥1 g/m2, ≤2 g/m2 twice daily)] and low-dose Ara-C [LDAraC (
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