Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase

Susan O'Brien, Francis Giles, Moshe Talpaz, Jorge Cortes, Mary Beth Rios, Jianqin Shan, Deborah Thomas, Michael Andreeff, Steven Kornblau, Stefan Faderl, Guillermo Garcia-Manero, Kevin White, Susie Mallard, Emil Freireich, Hagop M. Kantarjian

Research output: Contribution to journalReview article

Abstract

BACKGROUND. Before the discovery of imatinib mesylate, a Bcr-Abl selective tyrosine kinase inhibitor, three agents, interferon-alpha (IFN-α), cytarabine (ara-C), and homoharringtonine (HHT), had demonstrated activity against Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) as single agents and in couplet combinations. The goals of the current study were to evaluate the efficacy of the triple combination regimen with IFN-α, ara-C, and HHT in newly diagnosed Ph-positive CML and to assess the impact of the added sequential therapy with imatinib on overall prognosis. METHODS. Ninety patients with Ph-positive CML in early chronic phase received the triple regimen. Therapy consisted of 5 million units (MU)/m2 IFN-α subcutaneously (s.c. daily, ara-C 10 mg s.c. daily, and HHT 2.5 mg/m2 by continuous infusion over 24 hours daily × 5 every month. After a median duration of 16.5 months of therapy, 78 patients had their therapy changed to 400 mg orally administered imatinib daily. RESULTS. With the triple regimen, 85 patients (94%) achieved complete hematologic response and 67 patients (74%) had a cytogenetic response (Ph suppression to ≥ 90%) which was complete (Ph 0%) in 20 patients (22%) and major in 42 patients (46%). Myelosuppression was significant, resulting in considerable reductions in the dose schedules. After 12 months of therapy, the median IFN-α dose was 1.6 MU/m2 daily, the median ara-C dose was 1.85 mg daily, and the median number of HHT days was 2 every month. Only three patients developed blastic phase while receiving the triple regimen. With the change to imatinib therapy, currently 57 patients (63%) are in complete cytogenetic response and 69 patients (76%) in major cytogenetic response. With a median follow-up time of 46 months for the total study group, the estimated 5-year survival rate was 88%, and only 8 patients (9%) to date have developed blastic phase. CONCLUSIONS. The sequence of IFN-α, ara-C, and HHT followed by imatinib (imposed by the discovery of the latter drug) resulted in an estimated 5-year survival rate of 88%. This finding suggests that imatinib combination regimens may improve the prognosis in CML.

Original languageEnglish (US)
Pages (from-to)888-893
Number of pages6
JournalCancer
Volume98
Issue number5
DOIs
StatePublished - Sep 1 2003
Externally publishedYes

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Philadelphia Chromosome
Cytarabine
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Interferon-alpha
Cytogenetics
Therapeutics
bcr-abl Fusion Proteins
Survival Rate
Imatinib Mesylate
homoharringtonine
Drug Discovery
Appointments and Schedules

Keywords

  • Chronic myeloid leukemia
  • Cytarabine
  • Homoharringtonine
  • Interferon-alpha

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase. / O'Brien, Susan; Giles, Francis; Talpaz, Moshe; Cortes, Jorge; Rios, Mary Beth; Shan, Jianqin; Thomas, Deborah; Andreeff, Michael; Kornblau, Steven; Faderl, Stefan; Garcia-Manero, Guillermo; White, Kevin; Mallard, Susie; Freireich, Emil; Kantarjian, Hagop M.

In: Cancer, Vol. 98, No. 5, 01.09.2003, p. 888-893.

Research output: Contribution to journalReview article

O'Brien, S, Giles, F, Talpaz, M, Cortes, J, Rios, MB, Shan, J, Thomas, D, Andreeff, M, Kornblau, S, Faderl, S, Garcia-Manero, G, White, K, Mallard, S, Freireich, E & Kantarjian, HM 2003, 'Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase', Cancer, vol. 98, no. 5, pp. 888-893. https://doi.org/10.1002/cncr.11620
O'Brien, Susan ; Giles, Francis ; Talpaz, Moshe ; Cortes, Jorge ; Rios, Mary Beth ; Shan, Jianqin ; Thomas, Deborah ; Andreeff, Michael ; Kornblau, Steven ; Faderl, Stefan ; Garcia-Manero, Guillermo ; White, Kevin ; Mallard, Susie ; Freireich, Emil ; Kantarjian, Hagop M. / Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase. In: Cancer. 2003 ; Vol. 98, No. 5. pp. 888-893.
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title = "Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase",
abstract = "BACKGROUND. Before the discovery of imatinib mesylate, a Bcr-Abl selective tyrosine kinase inhibitor, three agents, interferon-alpha (IFN-α), cytarabine (ara-C), and homoharringtonine (HHT), had demonstrated activity against Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) as single agents and in couplet combinations. The goals of the current study were to evaluate the efficacy of the triple combination regimen with IFN-α, ara-C, and HHT in newly diagnosed Ph-positive CML and to assess the impact of the added sequential therapy with imatinib on overall prognosis. METHODS. Ninety patients with Ph-positive CML in early chronic phase received the triple regimen. Therapy consisted of 5 million units (MU)/m2 IFN-α subcutaneously (s.c. daily, ara-C 10 mg s.c. daily, and HHT 2.5 mg/m2 by continuous infusion over 24 hours daily × 5 every month. After a median duration of 16.5 months of therapy, 78 patients had their therapy changed to 400 mg orally administered imatinib daily. RESULTS. With the triple regimen, 85 patients (94{\%}) achieved complete hematologic response and 67 patients (74{\%}) had a cytogenetic response (Ph suppression to ≥ 90{\%}) which was complete (Ph 0{\%}) in 20 patients (22{\%}) and major in 42 patients (46{\%}). Myelosuppression was significant, resulting in considerable reductions in the dose schedules. After 12 months of therapy, the median IFN-α dose was 1.6 MU/m2 daily, the median ara-C dose was 1.85 mg daily, and the median number of HHT days was 2 every month. Only three patients developed blastic phase while receiving the triple regimen. With the change to imatinib therapy, currently 57 patients (63{\%}) are in complete cytogenetic response and 69 patients (76{\%}) in major cytogenetic response. With a median follow-up time of 46 months for the total study group, the estimated 5-year survival rate was 88{\%}, and only 8 patients (9{\%}) to date have developed blastic phase. CONCLUSIONS. The sequence of IFN-α, ara-C, and HHT followed by imatinib (imposed by the discovery of the latter drug) resulted in an estimated 5-year survival rate of 88{\%}. This finding suggests that imatinib combination regimens may improve the prognosis in CML.",
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TY - JOUR

T1 - Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase

AU - O'Brien, Susan

AU - Giles, Francis

AU - Talpaz, Moshe

AU - Cortes, Jorge

AU - Rios, Mary Beth

AU - Shan, Jianqin

AU - Thomas, Deborah

AU - Andreeff, Michael

AU - Kornblau, Steven

AU - Faderl, Stefan

AU - Garcia-Manero, Guillermo

AU - White, Kevin

AU - Mallard, Susie

AU - Freireich, Emil

AU - Kantarjian, Hagop M.

PY - 2003/9/1

Y1 - 2003/9/1

N2 - BACKGROUND. Before the discovery of imatinib mesylate, a Bcr-Abl selective tyrosine kinase inhibitor, three agents, interferon-alpha (IFN-α), cytarabine (ara-C), and homoharringtonine (HHT), had demonstrated activity against Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) as single agents and in couplet combinations. The goals of the current study were to evaluate the efficacy of the triple combination regimen with IFN-α, ara-C, and HHT in newly diagnosed Ph-positive CML and to assess the impact of the added sequential therapy with imatinib on overall prognosis. METHODS. Ninety patients with Ph-positive CML in early chronic phase received the triple regimen. Therapy consisted of 5 million units (MU)/m2 IFN-α subcutaneously (s.c. daily, ara-C 10 mg s.c. daily, and HHT 2.5 mg/m2 by continuous infusion over 24 hours daily × 5 every month. After a median duration of 16.5 months of therapy, 78 patients had their therapy changed to 400 mg orally administered imatinib daily. RESULTS. With the triple regimen, 85 patients (94%) achieved complete hematologic response and 67 patients (74%) had a cytogenetic response (Ph suppression to ≥ 90%) which was complete (Ph 0%) in 20 patients (22%) and major in 42 patients (46%). Myelosuppression was significant, resulting in considerable reductions in the dose schedules. After 12 months of therapy, the median IFN-α dose was 1.6 MU/m2 daily, the median ara-C dose was 1.85 mg daily, and the median number of HHT days was 2 every month. Only three patients developed blastic phase while receiving the triple regimen. With the change to imatinib therapy, currently 57 patients (63%) are in complete cytogenetic response and 69 patients (76%) in major cytogenetic response. With a median follow-up time of 46 months for the total study group, the estimated 5-year survival rate was 88%, and only 8 patients (9%) to date have developed blastic phase. CONCLUSIONS. The sequence of IFN-α, ara-C, and HHT followed by imatinib (imposed by the discovery of the latter drug) resulted in an estimated 5-year survival rate of 88%. This finding suggests that imatinib combination regimens may improve the prognosis in CML.

AB - BACKGROUND. Before the discovery of imatinib mesylate, a Bcr-Abl selective tyrosine kinase inhibitor, three agents, interferon-alpha (IFN-α), cytarabine (ara-C), and homoharringtonine (HHT), had demonstrated activity against Philadelphia chromosome (Ph)-positive chronic myelogenous leukemia (CML) as single agents and in couplet combinations. The goals of the current study were to evaluate the efficacy of the triple combination regimen with IFN-α, ara-C, and HHT in newly diagnosed Ph-positive CML and to assess the impact of the added sequential therapy with imatinib on overall prognosis. METHODS. Ninety patients with Ph-positive CML in early chronic phase received the triple regimen. Therapy consisted of 5 million units (MU)/m2 IFN-α subcutaneously (s.c. daily, ara-C 10 mg s.c. daily, and HHT 2.5 mg/m2 by continuous infusion over 24 hours daily × 5 every month. After a median duration of 16.5 months of therapy, 78 patients had their therapy changed to 400 mg orally administered imatinib daily. RESULTS. With the triple regimen, 85 patients (94%) achieved complete hematologic response and 67 patients (74%) had a cytogenetic response (Ph suppression to ≥ 90%) which was complete (Ph 0%) in 20 patients (22%) and major in 42 patients (46%). Myelosuppression was significant, resulting in considerable reductions in the dose schedules. After 12 months of therapy, the median IFN-α dose was 1.6 MU/m2 daily, the median ara-C dose was 1.85 mg daily, and the median number of HHT days was 2 every month. Only three patients developed blastic phase while receiving the triple regimen. With the change to imatinib therapy, currently 57 patients (63%) are in complete cytogenetic response and 69 patients (76%) in major cytogenetic response. With a median follow-up time of 46 months for the total study group, the estimated 5-year survival rate was 88%, and only 8 patients (9%) to date have developed blastic phase. CONCLUSIONS. The sequence of IFN-α, ara-C, and HHT followed by imatinib (imposed by the discovery of the latter drug) resulted in an estimated 5-year survival rate of 88%. This finding suggests that imatinib combination regimens may improve the prognosis in CML.

KW - Chronic myeloid leukemia

KW - Cytarabine

KW - Homoharringtonine

KW - Interferon-alpha

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U2 - 10.1002/cncr.11620

DO - 10.1002/cncr.11620

M3 - Review article

C2 - 12942553

AN - SCOPUS:0041887168

VL - 98

SP - 888

EP - 893

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 5

ER -