title: Randomized comparison of DAT versus ADE as induction chemotherapy in children and younger adults with acute myeloid leukemia. Results of the Medical Research Council's 10th AML trial (MRC AML10). Adult and Childhood Leukaemia Working Parties of the Medical Research Council.
abstract: The relative efficacy and toxicity of the chemotherapeutic agents thioguanine (6TG) and etoposide (VP16) were assessed by a randomized comparison of the DAT (daunorubicin, cytarabine, thioguanine) versus ADE (daunorubicin, cytarabine, etoposide) regimens in the Medical Research Council's 10th acute myeloid leukaemia trial (MRC AML 10), which was open to patient entry from May 1988 to April 1995. In this, the largest reported trial of AML therapy to date, 1,857 eligible patients, mostly less than 56 years old, were randomized: 929 (including 143 children under 15 years old) were allocated to DAT and 928 (143 children) to ADE. The two groups were well matched for presentation features. The complete remission (CR) rate was 81% with DAT and 83% with ADE (P = .3). The percentages of remitters achieving remission after 1, 2, or more than 2 courses were 70%, 22%, and 8% for DAT and 74%, 21%, and 5% for ADE. The percentages failing to achieve a CR due to resistant disease were 11% with DAT versus 9% with ADE (P = .07). There was a slightly higher death rate in CR during consolidation chemotherapy with ADE (9%) than with DAT (6%) (P = .06). Patients receiving DAT took slightly but significantly longer to recover from neutropenia and thrombocytopenia but the median number of days in hospital were similar in each group. ADE patients experienced slightly more severe nonhematologic toxicity. There was also no significant difference between the groups in the longer-term measures of efficacy: disease-free survival at 6 years from CR was 42% (+/-4) for DAT and 43% (+/-4) for ADE (P = .8); relapse rate at 6 years was 50% (+/-4) for DAT and 49% (+/-5) for ADE (P = .6); survival at 6 years was 40% (+/-4) for both DAT and ADE (P = .9). Subgroup analysis failed to show any benefit for etoposide in patients with monocytic or myelomonocytic disease, or in any other diagnostic subgroup. In conclusion, DAT and ADE both achieve high remission rates and good long-term survival, and are equally effective chemotherapy regimens for the treatment of AML patients aged up to 55 years.
authors.affiliation: Medical Research Council, London, UK.
authors.forename: I M
authors.initials: IM
authors.lastname: Hann
authors.forename: R F
authors.initials: RF
authors.lastname: Stevens
authors.forename: A H
authors.initials: AH
authors.lastname: Goldstone
authors.forename: J K
authors.initials: JK
authors.lastname: Rees
authors.forename: K
authors.initials: K
authors.lastname: Wheatley
authors.forename: R G
authors.initials: RG
authors.lastname: Gray
authors.forename: A K
authors.initials: AK
authors.lastname: Burnett
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D007223:Infant; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000401:mortality; D015993:Life Tables; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000401:mortality; D010349:Patient Compliance; D012074:Remission Induction; D016019:Survival Analysis; D013866:Thioguanine / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D003561:Cytarabine; D005047:Etoposide; D013866:Thioguanine; D006854:Hydrocortisone; D008727:Methotrexate; D003630:Daunorubicin