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Prepublished online as a Blood First Edition Paper on August 1, 2002; DOI 10.1182/blood-2001-12-0354.

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Blood, 1 December 2002, Vol. 100, No. 12, pp. 3869-3876

CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS

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

Jeanne E. Anderson, Kenneth J. Kopecky, Cheryl L. Willman, David Head, Margaret R. O'Donnell, Frederick W. Luthardt, Thomas H. Norwood, I-Ming Chen, Stanley P. Balcerzak, David B. Johnson, and Frederick R. Appelbaum

From the Katmai Oncology Group, Anchorage, AK; Southwest Oncology Group Statistical Center and the Puget Sound Oncology Consortium, Seattle, WA; University of New Mexico, Albuquerque; Vanderbilt University Medical Center, Nashville, TN; City of Hope National Medical Center, Duarte, CA; Ohio State University Health Center, Columbus, OH; and Wichita Community Clinical Oncology Program, KS.

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/m2 per day × 5) and etoposide (100 mg/m2 per day × 5) [ME], or cytarabine (200 mg/m2 per day × 7) and daunorubicin (45 mg/m2 per day × 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.

© 2002 by The American Society of Hematology.
 

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