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.
Publication types
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Clinical Trial
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Controlled Clinical Trial
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Research Support, Non-U.S. Gov't
MeSH terms
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Acute Disease
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Adolescent
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Adult
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Age Factors
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Aminoglycosides / administration & dosage
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Aminoglycosides / adverse effects
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Amsacrine / administration & dosage
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / adverse effects
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Antibodies, Monoclonal, Humanized
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Chemical and Drug Induced Liver Injury / etiology
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Cohort Studies
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Cytarabine / administration & dosage
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Doxorubicin / administration & dosage
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Etoposide / administration & dosage
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Feasibility Studies
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Gemtuzumab
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Granulocyte Colony-Stimulating Factor / administration & dosage
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Humans
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Idarubicin / administration & dosage
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Leukemia, Myeloid / drug therapy*
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Middle Aged
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Pilot Projects
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Remission Induction
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Thioguanine / administration & dosage
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Thioguanine / adverse effects
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Vidarabine / administration & dosage
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Vidarabine / analogs & derivatives
Substances
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Aminoglycosides
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Amsacrine
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Cytarabine
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Granulocyte Colony-Stimulating Factor
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Etoposide
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Doxorubicin
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Gemtuzumab
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Vidarabine
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Thioguanine
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Idarubicin
Supplementary concepts
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ACE protocol 2
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ACT protocol
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FLAG protocol