title: Outcome after induction chemotherapy for older patients with acute myeloid leukemia is not improved with mitoxantrone and etoposide compared to cytarabine and daunorubicin: a Southwest Oncology Group study.
abstract: Complete remission and long-term survival rates are low for older adults treated for acute myeloid leukemia (AML). Because of favorable phase 2 data using mitoxantrone and etoposide, we conducted a phase 3 study (SWOG-9333) in which patients over 55 years of age with previously untreated AML were randomized to receive mitoxantrone (10 mg/m(2) per day x 5) and etoposide (100 mg/m(2) per day x 5) [ME], or cytarabine (200 mg/m(2) per day x 7) and daunorubicin (45 mg/m(2) per day x 3) [AD] as induction therapy. The randomization was stratified by age, onset of leukemia, and multidrug resistance phenotype. Over a 4-year period, 328 eligible patients from 66 institutions were enrolled. The complete remission rate was 34% (95% confidence interval [CI] 26%-41%) for patients in the ME and 43% (CI 35%-51%) for patients in the AD treatment arm (one-tailed P value.96). The rates of resistant disease were 43% (CI 35%-51%) and 34% (CI 27%-42%), respectively, for the 2 treatment arms (one-tailed P value.95). The estimated overall survival at 2 years was 11% (CI 6%-15%) and 19% (CI 12%-25%) for patients randomized to ME and to AD induction therapy, respectively (one-tailed P value.99). After accounting for the independent prognostic factors associated with survival (karyotype, performance status, age, white blood cell count), exploratory analysis suggested there was a worse survival for patients who received ME compared with AD induction therapy (2-tailed P value.0066). We conclude that the results of our study do not demonstrate any benefit to the use of ME induction chemotherapy instead of AD in older patients with AML.
authors.affiliation: Katmai Oncology Group, Anchorage, AK, USA. jeanderson@ak.net
authors.forename: Jeanne E
authors.initials: JE
authors.lastname: Anderson
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Kopecky
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Willman
authors.forename: David
authors.initials: D
authors.lastname: Head
authors.forename: Margaret R
authors.initials: MR
authors.lastname: O'Donnell
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Luthardt
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Norwood
authors.forename: I-Ming
authors.initials: IM
authors.lastname: Chen
authors.forename: Stanley P
authors.initials: SP
authors.lastname: Balcerzak
authors.forename: David B
authors.initials: DB
authors.lastname: Johnson
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
mesh_terms: D000208:Acute Disease; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000633:toxicity; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D012074:Remission Induction / Q000379:methods; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone; D003630:Daunorubicin