High-dose liposomal daunorubicin and high-dose cytarabine combination in patients with refractory or relapsed acute myelogenous leukemia

Jorge Cortes, Elihu Estey, Susan O'Brien, Francis Giles, Yu Shen, Charles Koller, Miloslav Beran, Deborah Thomas, Michael Keating, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Liposomal encapsulation of daunorubicin (DaunoXome, DNX; Nexstar Pharmaceutical, Boulder, CO) changes the pharmacology profile to increase delivery to tumor sites and decrease toxicity. The authors investigated the effect of daunorubicin in combination with ara-C in patients with refractory or recurring acute myelogenous leukemia (AML). PATIENTS AND METHODS. Sixty-two patients with refractory or recurring AML received escalating doses of daunorubicin of 75, 100, 125, or 135 mg/m2 daily for 3 days together with ara-C 1 g/m2 intravenous continuous infusion daily for 4 days. RESULTS. Eighteen patients (29%) achieved a complete remission (CR) and 7 (11%) a hematologic improvement (i.e., met all criteria for CR except for platelet count < 100 × 109/L) for an overall response rate of 40%. The dose-limiting toxicity was mucositis in 4 in 9 (44%) patients treated at the 150 mg/m2 dose level, but minimal at 125 mg/m2 (2 of 32, 6%) or 135 mg/m2 (1 of 13, 8%). Cardiotoxicity Grade 2 was observed in 4 patients (6%) and Grade 3 or higher in 4 patients (6%). The median CR duration was 63 weeks, and overall survival rate was 25 weeks, with 28% patients alive after 1 year. CONCLUSIONS. The combination of DNX (or liposomal daunorubicin) and ara-C has significant antileukemia activity with acceptable toxicity. Further studies are warranted to investigate the role of high-dose anthracyclines in frontline AML therapy.

Original languageEnglish (US)
Pages (from-to)7-14
Number of pages8
JournalCancer
Volume92
Issue number1
DOIs
StatePublished - Jul 1 2001
Externally publishedYes

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Daunorubicin
Cytarabine
Acute Myeloid Leukemia
Mucositis
Anthracyclines
Carbon Monoxide
Platelet Count
Intravenous Infusions
Survival Rate
Pharmacology
Pharmaceutical Preparations

Keywords

  • Acute myeloid leukemia, liposomal daunorubicin, cytarabine, anthracyclines

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

High-dose liposomal daunorubicin and high-dose cytarabine combination in patients with refractory or relapsed acute myelogenous leukemia. / Cortes, Jorge; Estey, Elihu; O'Brien, Susan; Giles, Francis; Shen, Yu; Koller, Charles; Beran, Miloslav; Thomas, Deborah; Keating, Michael; Kantarjian, Hagop.

In: Cancer, Vol. 92, No. 1, 01.07.2001, p. 7-14.

Research output: Contribution to journalArticle

Cortes, Jorge ; Estey, Elihu ; O'Brien, Susan ; Giles, Francis ; Shen, Yu ; Koller, Charles ; Beran, Miloslav ; Thomas, Deborah ; Keating, Michael ; Kantarjian, Hagop. / High-dose liposomal daunorubicin and high-dose cytarabine combination in patients with refractory or relapsed acute myelogenous leukemia. In: Cancer. 2001 ; Vol. 92, No. 1. pp. 7-14.
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T1 - High-dose liposomal daunorubicin and high-dose cytarabine combination in patients with refractory or relapsed acute myelogenous leukemia

AU - Cortes, Jorge

AU - Estey, Elihu

AU - O'Brien, Susan

AU - Giles, Francis

AU - Shen, Yu

AU - Koller, Charles

AU - Beran, Miloslav

AU - Thomas, Deborah

AU - Keating, Michael

AU - Kantarjian, Hagop

PY - 2001/7/1

Y1 - 2001/7/1

N2 - BACKGROUND. Liposomal encapsulation of daunorubicin (DaunoXome, DNX; Nexstar Pharmaceutical, Boulder, CO) changes the pharmacology profile to increase delivery to tumor sites and decrease toxicity. The authors investigated the effect of daunorubicin in combination with ara-C in patients with refractory or recurring acute myelogenous leukemia (AML). PATIENTS AND METHODS. Sixty-two patients with refractory or recurring AML received escalating doses of daunorubicin of 75, 100, 125, or 135 mg/m2 daily for 3 days together with ara-C 1 g/m2 intravenous continuous infusion daily for 4 days. RESULTS. Eighteen patients (29%) achieved a complete remission (CR) and 7 (11%) a hematologic improvement (i.e., met all criteria for CR except for platelet count < 100 × 109/L) for an overall response rate of 40%. The dose-limiting toxicity was mucositis in 4 in 9 (44%) patients treated at the 150 mg/m2 dose level, but minimal at 125 mg/m2 (2 of 32, 6%) or 135 mg/m2 (1 of 13, 8%). Cardiotoxicity Grade 2 was observed in 4 patients (6%) and Grade 3 or higher in 4 patients (6%). The median CR duration was 63 weeks, and overall survival rate was 25 weeks, with 28% patients alive after 1 year. CONCLUSIONS. The combination of DNX (or liposomal daunorubicin) and ara-C has significant antileukemia activity with acceptable toxicity. Further studies are warranted to investigate the role of high-dose anthracyclines in frontline AML therapy.

AB - BACKGROUND. Liposomal encapsulation of daunorubicin (DaunoXome, DNX; Nexstar Pharmaceutical, Boulder, CO) changes the pharmacology profile to increase delivery to tumor sites and decrease toxicity. The authors investigated the effect of daunorubicin in combination with ara-C in patients with refractory or recurring acute myelogenous leukemia (AML). PATIENTS AND METHODS. Sixty-two patients with refractory or recurring AML received escalating doses of daunorubicin of 75, 100, 125, or 135 mg/m2 daily for 3 days together with ara-C 1 g/m2 intravenous continuous infusion daily for 4 days. RESULTS. Eighteen patients (29%) achieved a complete remission (CR) and 7 (11%) a hematologic improvement (i.e., met all criteria for CR except for platelet count < 100 × 109/L) for an overall response rate of 40%. The dose-limiting toxicity was mucositis in 4 in 9 (44%) patients treated at the 150 mg/m2 dose level, but minimal at 125 mg/m2 (2 of 32, 6%) or 135 mg/m2 (1 of 13, 8%). Cardiotoxicity Grade 2 was observed in 4 patients (6%) and Grade 3 or higher in 4 patients (6%). The median CR duration was 63 weeks, and overall survival rate was 25 weeks, with 28% patients alive after 1 year. CONCLUSIONS. The combination of DNX (or liposomal daunorubicin) and ara-C has significant antileukemia activity with acceptable toxicity. Further studies are warranted to investigate the role of high-dose anthracyclines in frontline AML therapy.

KW - Acute myeloid leukemia, liposomal daunorubicin, cytarabine, anthracyclines

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