High-Dose Versus Intermediate Dose Cytosine Arabinoside Combined with Mitoxantrone for the Treatment of Relapsed and Refractory Acute Myeloid Leukemia: Results of an Age Adjusted Randomized Comparison

Abstract

193 patients with relapsed or refractory acute myeloid leukemia (AML) were entered into a prospective randomized comparison of high-dose versus intermediate dose cytosine arabinoside (AraC) both combined with mitoxantrone (mitox) according to the previously established sequential HD-AraC/mitox regimen (S-HAM). AraC was administered by 3 hr inf. q 12 hrs on days 1, 2, and 8, 9 at randomly assigned doses of either 3.0 versus 1.0 g/m2 in pts. < 60 years of age or 1.0 versus 0.5 g/m2 in older pts. Mitox was given to all cases at a dose of 10 mg/m2/d on days 3, 4, and 10, 11. Randomization was stratified for primary refractoriness against induction therapy and the length of first remission in relapsed cases (< 6 mths., 6-18 mths., > 18 mths.). From 151 presently evaluable cases 72 pts (48%) achieved a complete remission (CR), 38 cases (25%) were non-responders (NR) and 41 pts. (27%) died within the first 6 weeks after the start of treatment (early death = ED). No significant differences were found in CR rates being 52% and 44% for the 3.0 versus 1.0 g/m2 AraC regimens in pts. < 60 years and 48% and 45% after 1.0 versus 0.5 g/m2 AraC in older pts. No differences between the respective regimens emerged either for the time to CR (median 46 days) nor remission duration (median 4.5 mths). Analysis of treatment failures, however, demonstrated a significantly higher rate of NR after the lower dose regimens in both age groups of 41% and 32% versus 11% and 14% in pts. receiving AraC at higher doses (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Improved treatment results for childhood acute myeloid leukemia in Taiwan

“…57 In adult patients younger than 60 years, induction therapy with mitoxantrone and Ara-C, in randomized doses of 1 or 3 g/m 2 /dose, resulted in similar remission rates, although CNS toxicity was more frequent in the Ara-C 3 g/m 2 group than in the 1 g/m 2 group (79 versus 28%, Po0.10). 58 This finding promotes the rationale for the use of the Ara-C 1 g/m 2 /dose rather than 3 g/m 2 in the present study.…”

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

“…Even upfront therapy of AML is associated with higher complication rates in reported studies. Reported TRM with induction upfront therapy is around 10-20% [29,30], and reported TRM during induction for salvage therapy is 15-25% [26,27]. The rate of the intensive care unit transfer during salvage induction and subsequent consolidation was 11% for 27 cycles of FCE, which is a lower rate than the 28% observed in an analysis for standard front-line therapy for AML [30].…”

“…Chemotherapy regimens commonly used include a high-dose cytarabine, clofarabine, etoposide, mitoxantrone and fludarabine-based combination in patients who are able to tolerate intensive therapy, and only one third of the patients who receive intensive salvage therapy are expected to achieve CR [22,23,24,25,26,27]. Fludarabine-based combinations are active salvage AML therapies that are non-cross resistant to anthracyclines, and therefore, have the potential to overcome P-glycoprotein-mediated multidrug resistance in relapsed/refractory AML [28].…”

Attitude towards remission induction for elderly patients with acute myeloid leukemia influences survival

“…Most young patients are considered eligible for remission induction, postremission treatment with or without stem cell transplantation, and second-line therapy at relapse, and the overall cure rate is about 40%. 3,4 The outcome for elderly patients with AML remains, however, dismal, [5][6][7][8][9][10][11][12][13] since fewer patients are eligible for remission induction, the remission rate is lower, and the remission duration shorter. Older patients more often have adverse risk factors, 14,15 and comorbidities may result in less tolerance for intensive therapy.…”