Sequential homoharringtonine and interferon-alpha in the treatment of early chronic phase chronic myelogenous leukemia.

Abstract

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.

• Authors: S O'Brien, H Kantarjian, C Koller, E Feldman, M Beran, M Andreeff, S Giralt, B Cheson, M Keating, E Freireich, M B Rios, M Talpaz
• Journal: Blood (Blood) Vol. 93 Issue 12 Pg. 4149-53 (Jun 15 1999) ISSN: 0006-4971 [Print] United States
• PMID: 10361112 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Harringtonines
• Interferon-alpha
• Homoharringtonine

Topics

• Adult
• Aged
• Antineoplastic Agents, Phytogenic (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Granulocytes
• Harringtonines (administration & dosage, adverse effects)
• Hematopoietic Stem Cell Transplantation
• Homoharringtonine
• Humans
• Interferon-alpha (administration & dosage, adverse effects)
• Karyotyping
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive (genetics, therapy)
• Leukocyte Count
• Middle Aged
• Platelet Count
• Remission Induction
• Thrombocytopenia (chemically induced)