Pilot study of Mylotarg, idarubicin and cytarabine combination regimen in patients with primary resistant or relapsed acute myeloid leukemia.
OBJECTIVE
Mylotarg has moderate activity as a single agent in patients with CD33-positive refractory or relapsed acute myelogenous leukemia (AML). A combination of an anthracycline and cytarabine (ara-C) is the core of most AML induction regimens. We conducted a pilot study of Mylotarg combined with idarubicin and ara-C in patients with refractory or relapsed AML.


METHODS
Mylotarg was administered at 6 mg/m(2) intravenously on days 1 and 15, idarubicin 12 mg/m(2) daily on days 2 through 4, and ara-C at 1.5 g/m(2) daily on days 2 through 5 (MIA) RESULTS: Of 14 patients were treated, 4 (29%) had primary resistant AML, and 10 (71%) relapsed AML. The median age of the patients was 61 years (range 34-74 years). MIA induced complete remission (CR) in three patients (21%) and CR with incomplete platelet recovery (CRp) in three patients (21%). The median survival was 8 weeks (range 2-64 weeks), and the median failure-free survival of CR patients was 27 weeks (range 11-64 weeks). All patients developed grade 3/4 myelosuppression - severe sepsis occurred in ten patients (71%). Other grade 3/4 nonhematologic toxicities included hepatic transaminitis, oral mucositis, and diarrhea. Two patients (14%) developed hepatic venoocclusive disease (VOD).


CONCLUSIONS
The addition of Mylotarg to idarubicin and ara-C is feasible. MIA has significant activity in patients with refractory AML. Hepatotoxicity and VOD are significant toxicities of Mylotarg-based combinations.
Alvarado
Yesid
Y
Department of Leukemia, The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, USA.
Tsimberidou
Apostolia
A
Kantarjian
Hagop
H
Cortes
Jorge
J
Garcia-Manero
Guillermo
G
Faderl
Stefan
S
Thomas
Deborah
D
Estey
Elihu
E
Giles
Francis J
FJ
D000328:Adult; D000368:Aged; D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm; D005260:Female; D000079982:Gemtuzumab; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D012008:Recurrence
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003561:Cytarabine; D000079982:Gemtuzumab; D015255:Idarubicin