Simultaneous homoharringtonine and interferon-α in the treatment of patients with chronic-phase chronic myelogenous leukemia

Susan O'Brien, Moshe Talpaz, Jorge Cortes, Jianqin Shan, Francis J. Giles, Stefan Faderl, Deborah Thomas, Guillermo Garcia-Manero, Susie Mallard, Mary BethRios, Charles Koller, Steve Kornblau, Michael Andreeff, Anthony Murgo, Michael Keating, Hagop M. Kantarjian

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Homoharringtonine (HHT) has antileukemic activity in patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). Combinations of HHT, interferon-α (IFN-α), and cytarabine (ara-C) have been studied in various CML phases. The objectives of this study were to evaluate the efficacy and toxicity profiles of a combination regimen of simultaneous HHT and IFN-α therapy in patients with chronic-phase CML who were not exposed previously to either agent. METHODS. Forty-seven patients were treated: 37 patients with early chronic-phase CML (2 patients with clonal evolution) and 10 patients with late chronic-phase CML. Their median age was 62 years (range, 23-73 years). HHT was given at a dose of 2.5 mg/m 2 by continuous intravenous infusion over 24 hours daily for 5 days every month, and IFN-α was given daily at a target dose of 5 × 10 6 units/m 2 subcutaneously. Response, survival, and treatment toxicity were analyzed. RESULTS. Overall, the complete hematologic response (CHR) rate was 85%; the cytogenetic response rate was 66%, with major cytogenetic responses (Ph positive in < 35% of metaphases) in 49% of patients and complete cytogenetic responses in 21% of patients. The CHR rate, cytogenetic response rate, and major cytogenetic response rate were 84%, 69%, and 52%, respectively, in patients with early chronicphase CML. Among the 10 patients with late chronic-phase CML, the CHR rate, cytogenetic response rate, and major cytogenetic response rate were 80%, 50%, and 40%, respectively. Response rates in patients age > 60 years were 84%, 62%, and 49% for CHR, cytogenetic response, and major cytogenetic response. Myelosuppression was frequent but manageable: Anemia with hemoglobin < 8.0 g/dL occurred in 36% of patients, requiring dose adjustments and erythropoietin therapy. Nonhematologic toxicities were mainly fatigue, aches, and gastrointestinal disturbances. Dose reductions with multiple courses were significant and were due to myelosuppression: After 6-24 courses, the median daily IFN-α dose was 1 MU/m 2, and the median number of days on HHT per month was 2 days. With a median follow-up of 26 months, the estimated 2-year survival rate was 90% (95% confidence interval, 79-100%). CONCLUSIONS. The simultaneous combination of HHT and IFN-α is safe and effective, but the dose schedules that actually were delivered were significantly lower than the planned dose schedules. With the availability of signal-transductior inhibitor 571 (imatinib mesylate), studies of combination of HHT and IFN-α chemotherapy in patients with CML who have disease that fails to respond to imatinib mesylate and of combinations with imatinib mesylate need to be explored.

Original languageEnglish (US)
Pages (from-to)2024-2032
Number of pages9
JournalCancer
Volume94
Issue number7
DOIs
StatePublished - Apr 1 2002
Externally publishedYes

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Leukemia, Myeloid, Chronic Phase
Interferons
Cytogenetics
Cytarabine
Therapeutics
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Appointments and Schedules
Clonal Evolution
Philadelphia Chromosome
homoharringtonine
Erythropoietin
Intravenous Infusions
Fatigue
Anemia
Hemoglobins
Survival Rate
Confidence Intervals
Drug Therapy
Pain
Survival

Keywords

  • Chronic myeloid/myelogenous leukemia
  • Chronic phase
  • Homoharringtonine
  • Interferon-α

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Simultaneous homoharringtonine and interferon-α in the treatment of patients with chronic-phase chronic myelogenous leukemia. / O'Brien, Susan; Talpaz, Moshe; Cortes, Jorge; Shan, Jianqin; Giles, Francis J.; Faderl, Stefan; Thomas, Deborah; Garcia-Manero, Guillermo; Mallard, Susie; BethRios, Mary; Koller, Charles; Kornblau, Steve; Andreeff, Michael; Murgo, Anthony; Keating, Michael; Kantarjian, Hagop M.

In: Cancer, Vol. 94, No. 7, 01.04.2002, p. 2024-2032.

Research output: Contribution to journalArticle

O'Brien, S, Talpaz, M, Cortes, J, Shan, J, Giles, FJ, Faderl, S, Thomas, D, Garcia-Manero, G, Mallard, S, BethRios, M, Koller, C, Kornblau, S, Andreeff, M, Murgo, A, Keating, M & Kantarjian, HM 2002, 'Simultaneous homoharringtonine and interferon-α in the treatment of patients with chronic-phase chronic myelogenous leukemia', Cancer, vol. 94, no. 7, pp. 2024-2032. https://doi.org/10.1002/cncr.10436
O'Brien, Susan ; Talpaz, Moshe ; Cortes, Jorge ; Shan, Jianqin ; Giles, Francis J. ; Faderl, Stefan ; Thomas, Deborah ; Garcia-Manero, Guillermo ; Mallard, Susie ; BethRios, Mary ; Koller, Charles ; Kornblau, Steve ; Andreeff, Michael ; Murgo, Anthony ; Keating, Michael ; Kantarjian, Hagop M. / Simultaneous homoharringtonine and interferon-α in the treatment of patients with chronic-phase chronic myelogenous leukemia. In: Cancer. 2002 ; Vol. 94, No. 7. pp. 2024-2032.
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abstract = "BACKGROUND. Homoharringtonine (HHT) has antileukemic activity in patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). Combinations of HHT, interferon-α (IFN-α), and cytarabine (ara-C) have been studied in various CML phases. The objectives of this study were to evaluate the efficacy and toxicity profiles of a combination regimen of simultaneous HHT and IFN-α therapy in patients with chronic-phase CML who were not exposed previously to either agent. METHODS. Forty-seven patients were treated: 37 patients with early chronic-phase CML (2 patients with clonal evolution) and 10 patients with late chronic-phase CML. Their median age was 62 years (range, 23-73 years). HHT was given at a dose of 2.5 mg/m 2 by continuous intravenous infusion over 24 hours daily for 5 days every month, and IFN-α was given daily at a target dose of 5 × 10 6 units/m 2 subcutaneously. Response, survival, and treatment toxicity were analyzed. RESULTS. Overall, the complete hematologic response (CHR) rate was 85{\%}; the cytogenetic response rate was 66{\%}, with major cytogenetic responses (Ph positive in < 35{\%} of metaphases) in 49{\%} of patients and complete cytogenetic responses in 21{\%} of patients. The CHR rate, cytogenetic response rate, and major cytogenetic response rate were 84{\%}, 69{\%}, and 52{\%}, respectively, in patients with early chronicphase CML. Among the 10 patients with late chronic-phase CML, the CHR rate, cytogenetic response rate, and major cytogenetic response rate were 80{\%}, 50{\%}, and 40{\%}, respectively. Response rates in patients age > 60 years were 84{\%}, 62{\%}, and 49{\%} for CHR, cytogenetic response, and major cytogenetic response. Myelosuppression was frequent but manageable: Anemia with hemoglobin < 8.0 g/dL occurred in 36{\%} of patients, requiring dose adjustments and erythropoietin therapy. Nonhematologic toxicities were mainly fatigue, aches, and gastrointestinal disturbances. Dose reductions with multiple courses were significant and were due to myelosuppression: After 6-24 courses, the median daily IFN-α dose was 1 MU/m 2, and the median number of days on HHT per month was 2 days. With a median follow-up of 26 months, the estimated 2-year survival rate was 90{\%} (95{\%} confidence interval, 79-100{\%}). CONCLUSIONS. The simultaneous combination of HHT and IFN-α is safe and effective, but the dose schedules that actually were delivered were significantly lower than the planned dose schedules. With the availability of signal-transductior inhibitor 571 (imatinib mesylate), studies of combination of HHT and IFN-α chemotherapy in patients with CML who have disease that fails to respond to imatinib mesylate and of combinations with imatinib mesylate need to be explored.",
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TY - JOUR

T1 - Simultaneous homoharringtonine and interferon-α in the treatment of patients with chronic-phase chronic myelogenous leukemia

AU - O'Brien, Susan

AU - Talpaz, Moshe

AU - Cortes, Jorge

AU - Shan, Jianqin

AU - Giles, Francis J.

AU - Faderl, Stefan

AU - Thomas, Deborah

AU - Garcia-Manero, Guillermo

AU - Mallard, Susie

AU - BethRios, Mary

AU - Koller, Charles

AU - Kornblau, Steve

AU - Andreeff, Michael

AU - Murgo, Anthony

AU - Keating, Michael

AU - Kantarjian, Hagop M.

PY - 2002/4/1

Y1 - 2002/4/1

N2 - BACKGROUND. Homoharringtonine (HHT) has antileukemic activity in patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). Combinations of HHT, interferon-α (IFN-α), and cytarabine (ara-C) have been studied in various CML phases. The objectives of this study were to evaluate the efficacy and toxicity profiles of a combination regimen of simultaneous HHT and IFN-α therapy in patients with chronic-phase CML who were not exposed previously to either agent. METHODS. Forty-seven patients were treated: 37 patients with early chronic-phase CML (2 patients with clonal evolution) and 10 patients with late chronic-phase CML. Their median age was 62 years (range, 23-73 years). HHT was given at a dose of 2.5 mg/m 2 by continuous intravenous infusion over 24 hours daily for 5 days every month, and IFN-α was given daily at a target dose of 5 × 10 6 units/m 2 subcutaneously. Response, survival, and treatment toxicity were analyzed. RESULTS. Overall, the complete hematologic response (CHR) rate was 85%; the cytogenetic response rate was 66%, with major cytogenetic responses (Ph positive in < 35% of metaphases) in 49% of patients and complete cytogenetic responses in 21% of patients. The CHR rate, cytogenetic response rate, and major cytogenetic response rate were 84%, 69%, and 52%, respectively, in patients with early chronicphase CML. Among the 10 patients with late chronic-phase CML, the CHR rate, cytogenetic response rate, and major cytogenetic response rate were 80%, 50%, and 40%, respectively. Response rates in patients age > 60 years were 84%, 62%, and 49% for CHR, cytogenetic response, and major cytogenetic response. Myelosuppression was frequent but manageable: Anemia with hemoglobin < 8.0 g/dL occurred in 36% of patients, requiring dose adjustments and erythropoietin therapy. Nonhematologic toxicities were mainly fatigue, aches, and gastrointestinal disturbances. Dose reductions with multiple courses were significant and were due to myelosuppression: After 6-24 courses, the median daily IFN-α dose was 1 MU/m 2, and the median number of days on HHT per month was 2 days. With a median follow-up of 26 months, the estimated 2-year survival rate was 90% (95% confidence interval, 79-100%). CONCLUSIONS. The simultaneous combination of HHT and IFN-α is safe and effective, but the dose schedules that actually were delivered were significantly lower than the planned dose schedules. With the availability of signal-transductior inhibitor 571 (imatinib mesylate), studies of combination of HHT and IFN-α chemotherapy in patients with CML who have disease that fails to respond to imatinib mesylate and of combinations with imatinib mesylate need to be explored.

AB - BACKGROUND. Homoharringtonine (HHT) has antileukemic activity in patients with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia (CML). Combinations of HHT, interferon-α (IFN-α), and cytarabine (ara-C) have been studied in various CML phases. The objectives of this study were to evaluate the efficacy and toxicity profiles of a combination regimen of simultaneous HHT and IFN-α therapy in patients with chronic-phase CML who were not exposed previously to either agent. METHODS. Forty-seven patients were treated: 37 patients with early chronic-phase CML (2 patients with clonal evolution) and 10 patients with late chronic-phase CML. Their median age was 62 years (range, 23-73 years). HHT was given at a dose of 2.5 mg/m 2 by continuous intravenous infusion over 24 hours daily for 5 days every month, and IFN-α was given daily at a target dose of 5 × 10 6 units/m 2 subcutaneously. Response, survival, and treatment toxicity were analyzed. RESULTS. Overall, the complete hematologic response (CHR) rate was 85%; the cytogenetic response rate was 66%, with major cytogenetic responses (Ph positive in < 35% of metaphases) in 49% of patients and complete cytogenetic responses in 21% of patients. The CHR rate, cytogenetic response rate, and major cytogenetic response rate were 84%, 69%, and 52%, respectively, in patients with early chronicphase CML. Among the 10 patients with late chronic-phase CML, the CHR rate, cytogenetic response rate, and major cytogenetic response rate were 80%, 50%, and 40%, respectively. Response rates in patients age > 60 years were 84%, 62%, and 49% for CHR, cytogenetic response, and major cytogenetic response. Myelosuppression was frequent but manageable: Anemia with hemoglobin < 8.0 g/dL occurred in 36% of patients, requiring dose adjustments and erythropoietin therapy. Nonhematologic toxicities were mainly fatigue, aches, and gastrointestinal disturbances. Dose reductions with multiple courses were significant and were due to myelosuppression: After 6-24 courses, the median daily IFN-α dose was 1 MU/m 2, and the median number of days on HHT per month was 2 days. With a median follow-up of 26 months, the estimated 2-year survival rate was 90% (95% confidence interval, 79-100%). CONCLUSIONS. The simultaneous combination of HHT and IFN-α is safe and effective, but the dose schedules that actually were delivered were significantly lower than the planned dose schedules. With the availability of signal-transductior inhibitor 571 (imatinib mesylate), studies of combination of HHT and IFN-α chemotherapy in patients with CML who have disease that fails to respond to imatinib mesylate and of combinations with imatinib mesylate need to be explored.

KW - Chronic myeloid/myelogenous leukemia

KW - Chronic phase

KW - Homoharringtonine

KW - Interferon-α

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