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

Hagop M. Kantarjian, Moshe Talpaz, Terry L. Smith, Jorge Cortes, Francis J. Giles, Mary Beth Rios, Susie Mallard, James Gajewski, Anthony Murgo, Bruce Cheson, Susan O'Brien

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3513-3521
Number of pages9
JournalJournal of Clinical Oncology
Volume18
Issue number20
DOIs
StatePublished - Oct 15 2000
Externally publishedYes

Fingerprint

Leukemia, Myeloid, Chronic Phase
Cytarabine
Interferon-alpha
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Treatment Failure
Cytogenetics
Clonal Evolution
Philadelphia Chromosome
Survival
Subcutaneous Injections
homoharringtonine
Headache
Diarrhea
Multivariate Analysis
Survival Rate
Clone Cells
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia. / Kantarjian, Hagop M.; Talpaz, Moshe; Smith, Terry L.; Cortes, Jorge; Giles, Francis J.; Rios, Mary Beth; Mallard, Susie; Gajewski, James; Murgo, Anthony; Cheson, Bruce; O'Brien, Susan.

In: Journal of Clinical Oncology, Vol. 18, No. 20, 15.10.2000, p. 3513-3521.

Research output: Contribution to journalArticle

Kantarjian, HM, Talpaz, M, Smith, TL, Cortes, J, Giles, FJ, Rios, MB, Mallard, S, Gajewski, J, Murgo, A, Cheson, B & O'Brien, S 2000, 'Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia', Journal of Clinical Oncology, vol. 18, no. 20, pp. 3513-3521. https://doi.org/10.1200/JCO.2000.18.20.3513
Kantarjian, Hagop M. ; Talpaz, Moshe ; Smith, Terry L. ; Cortes, Jorge ; Giles, Francis J. ; Rios, Mary Beth ; Mallard, Susie ; Gajewski, James ; Murgo, Anthony ; Cheson, Bruce ; O'Brien, Susan. / Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia. In: Journal of Clinical Oncology. 2000 ; Vol. 18, No. 20. pp. 3513-3521.
@article{95998b3cd3604d0fa9ec01049aefab9f,
title = "Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia",
abstract = "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.",
author = "Kantarjian, {Hagop M.} and Moshe Talpaz and Smith, {Terry L.} and Jorge Cortes and Giles, {Francis J.} and Rios, {Mary Beth} and Susie Mallard and James Gajewski and Anthony Murgo and Bruce Cheson and Susan O'Brien",
year = "2000",
month = "10",
day = "15",
doi = "10.1200/JCO.2000.18.20.3513",
language = "English (US)",
volume = "18",
pages = "3513--3521",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "20",

}

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

VL - 18

SP - 3513

EP - 3521

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 20

ER -