title: Mitoxantrone, cytosine arabinoside, and VP-16 in 36 patients with relapsed and refractory acute myeloid leukemia.
abstract: Mitoxantrone in combination with VP-16 proved to be effective in refractory and relapsed acute myeloid leukemia (AML), with 42% of patients achieving complete remission (CR). The aim of this study was to assess whether the addition of cytosine arabinoside increased the response rate at a tolerable toxicity. The regimen consisted of mitoxantrone (M) 10 mg/m2 i.v. days 4-8, cytosine arabinoside (A) 100 mg/m2 continuous infusion days 1-8, and etoposide (VP-16) (V) 100-120 mg/m2 i.v. days 4-8 (MAV protocol) for relapsed and refractory AML. Thirty-six patients were treated, with a median age of 51 (20-73) years. For induction therapy one to two MAV cycles and for consolidation therapy two courses were scheduled. Twenty-one (58.3%) patients attained a complete remission (CR), with a median duration of 4.5 (1-12+) months. The median survival of all patients was 5.5 (0.5-15.5+) months. Four patients died in CR from chronic infections or after consolidation therapy with MAV. In evaluable patients, times to greater than 500 granulocytes/microliters and greater than 25,000 platelets/microliters were 23 (7-46) and 23 (6-44) days, respectively. In 54 evaluable MAV courses the following toxicity was observed (WHO grades 3/4): 26%, nausea and vomiting: 9%, hemorrhage; 6%, bilirubinemia; 11%, diarrhea; 22%, mucositis; 6%, local infection; 20%, septicemia; 13%, fever of unknown origin; 2%, cardiac arrhythmia; 7%, congestive heart failure. We conclude that MAV therapy is a highly active antileukemic combination with acceptable toxicity, which is recommended for further clinical trials in untreated AML.
authors.affiliation: Dept. of Hematology-Oncology, Medical School, Hannover, FRG.
authors.forename: H
authors.initials: H
authors.lastname: Link
authors.forename: M
authors.initials: M
authors.lastname: Freund
authors.forename: H
authors.initials: H
authors.lastname: Diedrich
authors.forename: H
authors.initials: H
authors.lastname: Wilke
authors.forename: J
authors.initials: J
authors.lastname: Austein
authors.forename: M
authors.initials: M
authors.lastname: Henke
authors.forename: H
authors.initials: H
authors.lastname: Wandt
authors.forename: E
authors.initials: E
authors.lastname: Fackler-Schwalbe
authors.forename: G
authors.initials: G
authors.lastname: Schlimok
authors.forename: R
authors.initials: R
authors.lastname: Hoffmann
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D004341:Drug Evaluation; D005047:Etoposide / Q000008:administration & dosage; D005860:Germany, West / Q000453:epidemiology; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D015337:Multicenter Studies as Topic; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone