title: High-dose cytosine arabinoside and mitoxantrone: preliminary results of a pilot study with sequential application (S-HAM) indicating a high antileukemic activity in refractory acute leukemias.
abstract: In an attempt to further improve on the encouraging results achieved by high-dose cytosine arabinoside (HD AraC) and mitoxantrone (HAM) in refractory acute leukemias, a timely modified sequential schedule of both drugs was developed (S-HAM) and applied to 13 patients with far advanced acute leukemias, 8 of whom had been treated with the original HAM protocol before. Based on the cell kinetic and pharmacokinetic rationale outlined by Capizzi et al., HD AraC 3 g/m2 was applied every 12 h on days 1 and 2 followed by mitoxantrone 10 mg/m2/day on days 3 and 4. After 3 days without therapy the identical sequence was repeated on days 8 and 9 (HD AraC) and 10 and 11 (mitoxantrone), respectively. Of the 13 patients 9 (69%) achieved a complete remission, 2 were resistant and 2 were early deaths. Six of the 8 patients with prior HAM treatment obtained a further complete remission with S-HAM. In 2 of these patients a longer remission was induced by S-HAM than by the preceding original HAM treatment. Although these data are preliminary and need confirmation on larger numbers of patients, they strongly suggest a high antileukemic activity of the S-HAM protocol which may even be superior to the previously used HAM regimen.
authors.affiliation: Department of Internal Medicine, University of Münster, FRG.
authors.forename: W
authors.initials: W
authors.lastname: Hiddemann
authors.forename: T
authors.initials: T
authors.lastname: Büchner
authors.forename: M
authors.initials: M
authors.lastname: Essink
authors.forename: O
authors.initials: O
authors.lastname: Koch
authors.forename: W
authors.initials: W
authors.lastname: Stenzinger
authors.forename: J
authors.initials: J
authors.lastname: van de Loo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D010865:Pilot Projects
chemical_list: D003561:Cytarabine; D008942:Mitoxantrone