Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia

Citation
Hm. Kantarjian et al., Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia, J CL ONCOL, 18(20), 2000, pp. 3513-3521
Citations number
40
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
JOURNAL OF CLINICAL ONCOLOGY
ISSN journal
0732183X → ACNP
Volume
18
Issue
20
Year of publication
2000
Pages
3513 - 3521
Database
ISI
SICI code
0732-183X(20001015)18:20<3513:HALCIT>2.0.ZU;2-F
Abstract
Purpose: To evaluate the efficacy and toxicity profiles of a combination re gimen of hamoharringtonine (HHT) and low-dose cytarabine (ara-C) in patient s with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia ( CML) who had experienced treatment failure with interferon alfa (IFN alpha) therapy. Patients and Methods: One hundred five patients were treated: 100 in chroni c phase (15 with cytogenetic clonal evolution) and five in accelerated phas e. Their median age was 52 years; all had been treated unsuccessfully with IFN alpha; 94% were in late chronic phase; 43% held been exposed to ara-C a nd 11% had been exposed to HHT. Patients received HHT 2.5 mg/m(2) by contin uous infusion daily for 5 days and ara-C 15 mg/m2 daily in two subcutaneous injections for 5 days every 4 weeks. The outcome of the 100 patients in ch ronic phase was compared with a previous study group of 73 patients treated with HHT alone. Results: Overall, the complete hematologic response (CHR) rate in chronic p hase was 72%; the cytogenetic response rate was 32% (major response, 15%; c omplete response, 5%). Toxicities were acceptable, mostly related to modera te diarrhea (3%), headaches (3%), cardiovascular events (3%), and myelosupp ression-associated complications (3% to 14%). With a median follow-up perio d of 25 months, the estimated 4-year survival rate wets 55%. Response rates were identical with HHT plus ara-C versus HHT alone, but the survival was significantly longer with the combination after accounting for diffrences i n the study groups and by multivariate analysis. Conclusion: The combination regimen of HHT and ara-C is effective and safe in patients with CML who have experienced treatment failure with IFN alpha and needs to be investigated together with IFN alpha as part of front-line CML therapy. The addition of ara-C did not improve the response rates but m ay have improved survival, perhaps through suppression of clones related to disease transformation. (C) 2000 by American Society of Clinical Oncology.