High antileukemic activity of sequential high dose cytosine arabinoside and mitoxantrone in patients with refractory acute leukemias. Results of a clinical phase II study.

BACKGROUND: The current study was initiated to assess the efficacy and side effects of a timed sequential application of high dose cytosine arabinoside (AraC) in combination with mitoxantrone (S-HAM) in patients with refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL).
METHODS: Patients with refractory AML or ALL were eligible for S-HAM salvage therapy, which was comprised of AraC, 1 g/m2 or 3 g/m2 every 12 hours, on Days 1, 2, 8, and 9 and mitoxantrone, 10 mg/m2/day, given on Days 3, 4, 10, and 11.
RESULTS: Of 22 fully evaluable patients, 14 patients (64%) achieved a complete remission whereas 5 patients (23%) succumbed to early death and 3 patients (14%) did not respond. Blood counts recovered at a median of 33.5 days after the start of treatment and complete remission was achieved after a median of 38 days. The median duration of complete remission was 4 months (range, 1-14 months) whereas overall survival time lasted for a median of 4.5 months (range, 1-30+ months). Treatment-associated toxicity was comprised predominantly of infection and diarrhea that reached World Health Organization Grades 3 and 4 in 64% and 32% of patients, respectively. Complementary pharmacokinetic evaluations of plasma AraC and AraU levels revealed no impact of initial AraC administration on the pharmacokinetics of subsequent AraC administrations and failed to demonstrate any evidence of self-potentiation.
CONCLUSIONS: The clinical data show the S-HAM regimen to be a promising approach for the treatment of patients with advanced acute leukemias. However, further evaluation at earlier stages of treatment is needed.