Sequential homoharringtonine and interferon-alpha in the treatment of early chronic phase chronic myelogenous leukemia.
Homoharringtonine (HHT) is a novel plant alkaloid that produced a complete hematologic remission (CHR) in 72% of patients with late chronic phase chronic myelogenous leukemia (CML). Cytogenetic (CG) remissions were noted in 31%. In this study, six courses of HHT were administered to 90 patients with early chronic phase CML (< 1 year from diagnosis). Patients then received interferon-alpha (IFN-alpha) with a target dose of 5 MU/m2 daily. Results were compared with those in a prior group of patients treated with IFN-alpha-based therapy between 1982 and 1990. Ninety-two percent of patients achieved CHR with HHT; CG responses were observed in 60% and were major in 27%. Both CHR and CG response rates were significantly higher than those seen in historical control patients after 6 months of IFN-alpha therapy. After receiving HHT, patients required lower doses of IFN-alpha to maintain a CHR. The median dose delivered was 2.4 MU/m2. This reduction in IFN-alpha dose was associated with a lower incidence of myalgia and gastrointestinal (GI) disturbances than that seen in patients treated at the 5 MU/m2 dose. Overall, CG responses were seen in 66% of the patients who received HHT and IFN-alpha compared with 61% of the historical control patients. HHT is a very effective treatment of early chronic phase CML, and ongoing trials are investigating the simultaneous administration of HHT and IFN-alpha, as well as that of HHT and low-dose cytosine arabinoside in patients failing IFN-alpha therapy.
O'Brien
S
S
Departments of Leukemia, Bioimmunotherapy, and Blood and Marrow Transplant, Division of Medicine, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Kantarjian
H
H
Koller
C
C
Feldman
E
E
Beran
M
M
Andreeff
M
M
Giralt
S
S
Cheson
B
B
Keating
M
M
Freireich
E
E
Rios
M B
MB
Talpaz
M
M
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D006098:Granulocytes; D006248:Harringtonines / Q000008:administration & dosage* / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation; D000077863:Homoharringtonine; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D007621:Karyotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000628:therapy*; D007958:Leukocyte Count; D008875:Middle Aged; D010976:Platelet Count; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced
D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D016898:Interferon-alpha; D000077863:Homoharringtonine