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
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.