title: Second-line mitoxantrone, etoposide, and cytarabine for acute myeloid leukemia: a single-center experience.
abstract: The majority of patients with acute myeloid leukemia (AML) will require second-line chemotherapy for either relapsed or refractory disease. Currently, only allogeneic hematopoietic cell transplantation (HCT) offers a curative option in this setting and no preferred regimen has been established. The reported efficacy of second-line regimens is widely disparate, thus limiting informed clinical decision making. A retrospective review of 77 patients receiving therapy between 2001 and 2008 with relapsed, 42, and refractory, 35, AML was performed to determine overall response rate and survival following mitoxantrone (8 mg/m(2)/day), etoposide (100 mg/m(2)/day), and cytarabine (1,000 mg/m(2)/day) chemotherapy administered over 5 days. Among 77 patients (median age of 54 years and 64% intermediate risk karyotype) with median follow-up of 153 days, 18% achieved a complete response and 8% a morphologic leukemia-free state. Fifty-seven (74%) experienced treatment failure, 10 of whom achieved a remission after additional therapy. Median overall survival (OS) was 6.8 months. Among patients achieving a response, 50% received consolidation with allogeneic HCT, autologous HCT (5%), or consolidation chemotherapy alone (45%). A nonsignificant trend in overall response (50%, 27%, and 23.8%) and median OS (8.3, 6.8, and 4.7 months) was observed by cytogenetic stratification into favorable, intermediate, and unfavorable risk. Patients with refractory versus relapsed disease had similar overall responses (20% and 31%, P = 0.41) and median OS (5.3 and 7.6 months, P = 0.36). Despite risk stratification by the European Prognostic Index, our series demonstrates inferior rates of response and survival, illustrating the limited activity of this regimen in our cohort.
authors.affiliation: Department of Medicine, Division of Hematology, Stanford University, Stanford, CA 94305, USA.
authors.forename: Holbrook E
authors.initials: HE
authors.lastname: Kohrt
authors.forename: Samit
authors.initials: S
authors.lastname: Patel
authors.forename: Michelle
authors.initials: M
authors.lastname: Ho
authors.forename: Terri
authors.initials: T
authors.lastname: Owen
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Pollyea
authors.forename: Ravindra
authors.initials: R
authors.lastname: Majeti
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.forename: Steve
authors.initials: S
authors.lastname: Coutre
authors.forename: Michaela
authors.initials: M
authors.lastname: Liedtke
authors.forename: Caroline
authors.initials: C
authors.lastname: Berube
authors.forename: Ash A
authors.initials: AA
authors.lastname: Alizadeh
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Medeiros
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D003561:Cytarabine / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage; D012074:Remission Induction; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods*; D015996:Survival Rate; D017211:Treatment Failure; D055815:Young Adult
chemical_list: D003561:Cytarabine; D005047:Etoposide; D008942:Mitoxantrone