TY - JOUR
T1 - Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia
AU - Kantarjian, Hagop M.
AU - Talpaz, Moshe
AU - Smith, Terry L.
AU - Cortes, Jorge
AU - Giles, Francis J.
AU - Rios, Mary Beth
AU - Mallard, Susie
AU - Gajewski, James
AU - Murgo, Anthony
AU - Cheson, Bruce
AU - O'Brien, Susan
PY - 2000/10/15
Y1 - 2000/10/15
N2 - Purpose: To evaluate the efficacy and toxicity profiles of a combination regimen of homoharringtonine (HHT) and low-dose cytarabine (ara-C) in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who had experienced treatment failure with interferon alfa (IFNα) therapy. Patients and Methods: One hundred five patients were treated: 100 in chronic phase (15 with cytogenetic clonal evolution) and five in accelerated phase. Their median age was 52 years; all had been treated unsuccessfully with IFNα; 94% were in late chronic phase; 43% had been exposed to ara-C and 11% had been exposed to HHT. Patients received HHT 2.5 mg/m2 by continuous 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 chronic 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 phase was 72%; the cytogenetic response rate was 32% (major response, 15%; complete response, 5%). Toxicities were acceptable, mostly related to moderate diarrhea (3%), headaches (3%), cardiovascular events (3%), and myelosuppression-associated complications (3% to 14%). With a median follow-up period of 25 months, the estimated 4-year survival rate was 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 differences in 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 IFNα and needs to be investigated together with IFNα as part of front-line CML therapy. The addition of ara-C did not improve the response rates but may have improved survival, perhaps through suppression of clones related to disease transformation. (C) 2000 by American Society of Clinical Oncology.
AB - Purpose: To evaluate the efficacy and toxicity profiles of a combination regimen of homoharringtonine (HHT) and low-dose cytarabine (ara-C) in patients with Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) who had experienced treatment failure with interferon alfa (IFNα) therapy. Patients and Methods: One hundred five patients were treated: 100 in chronic phase (15 with cytogenetic clonal evolution) and five in accelerated phase. Their median age was 52 years; all had been treated unsuccessfully with IFNα; 94% were in late chronic phase; 43% had been exposed to ara-C and 11% had been exposed to HHT. Patients received HHT 2.5 mg/m2 by continuous 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 chronic 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 phase was 72%; the cytogenetic response rate was 32% (major response, 15%; complete response, 5%). Toxicities were acceptable, mostly related to moderate diarrhea (3%), headaches (3%), cardiovascular events (3%), and myelosuppression-associated complications (3% to 14%). With a median follow-up period of 25 months, the estimated 4-year survival rate was 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 differences in 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 IFNα and needs to be investigated together with IFNα as part of front-line CML therapy. The addition of ara-C did not improve the response rates but may have improved survival, perhaps through suppression of clones related to disease transformation. (C) 2000 by American Society of Clinical Oncology.
UR - http://www.scopus.com/inward/record.url?scp=0034667856&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034667856&partnerID=8YFLogxK
U2 - 10.1200/JCO.2000.18.20.3513
DO - 10.1200/JCO.2000.18.20.3513
M3 - Article
C2 - 11032593
AN - SCOPUS:0034667856
SN - 0732-183X
VL - 18
SP - 3513
EP - 3521
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 20
ER -