A feasibility study of simultaneous administration of gemtuzumab ozogamicin with intensive chemotherapy in induction and consolidation in younger patients with acute myeloid leukemia.
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.
Kell
William J
WJ
Department of Haematology, University of Wales College of Medicine, Heath Park, Cardiff, CF14 4XN, Wales.
Burnett
Alan K
AK
Chopra
Raj
R
Yin
John A L
JA
Clark
Richard E
RE
Rohatiner
Ama
A
Culligan
Dominic
D
Hunter
Ann
A
Prentice
Archie G
AG
Milligan
Donald W
DW
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
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