High-dose cytarabine improves DFS in consolidation chemotherapy for AML
Twice-daily administration of high-dose cytarabine improves disease-free survival (DFS) in consolidation chemotherapy for acute myeloid leukaemia (AML) compared with twice-daily lower doses of cytarabine, according to a meta-analysis.
Researchers analysed 4,008 patients with AML aged 15–85 years from ten multicentre phase III/IV trials who were randomized to receive twice-daily doses of one of three cytarabine dose ranges: high-dose (>2 g/m2 to ≤3 g/m2), intermediate-dose (≥1 g/m2 to ≤2 g/m2), or low-dose (<1 g/m2). [Sci Rep 2017;doi:10.1038/s41598-017-10368-0]
DFS was improved with high- vs intermediate- and low-dose cytarabine (hazard ratio [HR], 0.87, 95 percent credible interval [CrI], 0.79–0.97 and HR, 0.86, 95 percent CrI, 0.78–0.95, respectively).
However, a higher risk of grade 3–4 nonhaematologic toxicity was observed with high- and intermediate- vs low-dose cytarabine (HR, 6.04, 95 percent CrI, 1.67–21.49 and HR, 3.80, 95 percent CrI, 1.05–12.85, respectively).
The findings substantiate the clinical value of high-dose cytarabine in delivering maximum antirelapse effect, said the researchers. “Though it is associated with grade 3–4 nonhaematologic toxicity … the toxic difference between the [high and intermediate] doses is nonsignificant.”
Approximately 80 percent of young adult patients achieve complete remission with cytarabine- and anthracycline-based chemotherapy; however, only one-third remain disease-free for over 5 years, the researchers pointed out. Furthermore, those in remission are likely to relapse without further therapy, thus requiring a suitable postremission regimen, they added.
As such, twice-daily administration of high-dose cytarabine was adopted as the standard postremission regimen for adult AML despite its high toxicity rate and cost. [Best Pract Res Clin Haematol 2008;21:53-60; Blood Cancer J 2016;6:e441] “Cytarabine … in consolidation therapy plays an important role in preventing relapses for AML patients [who have] achieved complete remission,” said the researchers.
Although intermediate-dose cytarabine presented a comparable therapeutic effect with, and less toxicity than, high-dose cytarabine, the latter remains the standard postremission regimen given the lack of consistent improvement with intermediate-dose cytarabine, said the researchers.
Researchers acknowledged that their findings need to be considered as average effects, as summarized data could not facilitate evaluation of clinically relevant subgroups. Additionally, given the inconsistencies regarding the toxic effects of cytarabine in some of the trials evaluated, the researchers recommended exercising caution when interpreting the toxicity findings.
Other chemotherapeutic agents could also have complemented the cytarabine-based therapy and contributed to the effective assessments, noted the researchers.