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 patient s with refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). METHODS. Patients with refractory AML or ALL were elig ible for S-HAM salvage therapy, which was comprised of AraC, 1 g/m(2) or 3 g/m(2) every 12 hours, on Days 1, 2, 8, and 9 and mitoxantrone, 1 0 mg/m(2)/day, given on Days 3, 4, 10, and 11. RESULTS. Of 22 fully ev aluable patients, 14 patients (64%) achieved a complete remission wher eas 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 th e start of treatment and complete remission was achieved after a media n 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, respect ively. Complementary pharmacokinetic evaluations of plasma AraC and Ar aU levels revealed no impact of initial AraC administration on the pha rmacokinetics of subsequent AraC administrations and failed to demonst rate any evidence of self-potentiation. CONCLUSIONS. The clinical data show the S-HAM regimen to be a promising approach for the treatment o f patients with advanced acute leukemias. However, further evaluation at earlier stages of treatment is needed. (C) 1997 American Cancer Soc iety.