title: A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia.
abstract: The feasibility of combining gemtuzumab ozogamicin (GO) with intensive chemotherapy as first-line treatment of acute myeloid leukemia (AML) was assessed in 72 patients, aged 17 to 59 years, as a prelude to the United Kingdom Medical Research Council (MRC) AML15 trial. Sixty-four patients received induction chemotherapy (DAT [daunorubicin, ara-C, thioguanine], DA [daunorubicin, ara-C], or FLAG-Ida [fludarabine, ara-C, G-CSF, idarubicin]) with GO on day 1. It was possible to give GO 3 mg/m2 with course 1, but 6 mg/m2 with course 1 or GO in a dose of 3 mg/m2 with consecutive courses was not feasible because of hepatotoxicity and delayed hematopoietic recovery. Thirty-one patients who were treated in consolidation with MACE (amsacrine, ara-C, etoposide) or HidAC (HidAC) and GO (3 mg/m2), and 23 in induction and consolidation, tolerated GO (3 mg/m2) well. Grade 4 liver toxicity and sinusoidal obstructive syndrome was more common in thioguanine-containing schedules (P =.007). Remission with course 1 was seen in 86% of patients. DA or FLAG-Ida with GO in induction achieved complete remission in 91% of patients and 78% of these patients are in continuous complete remission at 8 months. GO given with induction (DA or FLAG-Ida) and consolidation (MACE or HidAC) was well tolerated. These schedules are now being compared in the MRC AML15 trial in patients younger than 60 years.
authors.affiliation: Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, Wales.
authors.forename: William J
authors.initials: WJ
authors.lastname: Kell
authors.forename: Alan K
authors.initials: AK
authors.lastname: Burnett
authors.forename: Raj
authors.initials: R
authors.lastname: Chopra
authors.forename: John A L
authors.initials: JA
authors.lastname: Yin
authors.forename: Richard E
authors.initials: RE
authors.lastname: Clark
authors.forename: Ama
authors.initials: A
authors.lastname: Rohatiner
authors.forename: Dominic
authors.initials: D
authors.lastname: Culligan
authors.forename: Ann
authors.initials: A
authors.lastname: Hunter
authors.forename: Archie G
authors.initials: AG
authors.lastname: Prentice
authors.forename: Donald W
authors.initials: DW
authors.lastname: Milligan
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects; D000677:Amsacrine / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005240:Feasibility Studies; D000079982:Gemtuzumab; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007951:Leukemia, Myeloid / Q000188:drug therapy*; D008875:Middle Aged; D010865:Pilot Projects; D012074:Remission Induction; D013866:Thioguanine / Q000008:administration & dosage / Q000009:adverse effects; D014740:Vidarabine / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000677:Amsacrine; D003561:Cytarabine; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D004317:Doxorubicin; D000079982:Gemtuzumab; D014740:Vidarabine; D013866:Thioguanine; D015255:Idarubicin