Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during induction: Chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome

Gloria N. Mattiuzzi, Elihu Estey, Issam Raad, Francis Giles, Jorge Cortes, Yu Shen, Dimitrios Kontoyiannis, Charles Koller, Mark Munsell, Miloslav Beran, Hagop Kantarjian

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Fungal infections are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The authors evaluated the efficacy and toxicity of liposomal amphotericin B (L-AmB) compared with a combination of fluconazole plus itraconazole (F+I) as prophylaxis in this setting. METHODS. Patients with newly diagnosed AML or high-risk MDS who were undergoing initial induction chemotherapy were randomized to receive either F+I (fluconazole 200 mg orally every 12 hours plus itraconazole tablets 200 mg orally every 12 hours) or L-AmB (3 mg/kg intravenously 3 times per week) in this prospective, open-label study. RESULTS. Seventy-two L-AmB-treated patients and 67 F+I-treated patients were enrolled in the study. Of these, 47% of patients completed antifungal prophylaxis without a change in therapy for proven or suspected fungal infection. Three patients in each arm developed a proven fungal infection. Twenty-three percent of the L-AmB-treated patients and 24% of the F+I-treated patients were changed to alternative antifungal therapy because of persistent fever (P value not significant). Nine percent of the L-AmB-treated patients developed pneumonia of unknown etiology compared with 16% of the F+I-treated patients (P value not significant). Increases in serum creatinine levels to > 2 mg/dL (20% for the L-AmB arm vs. 6% for the F+I arm; P = 0.012) and increases in serum bilirubin levels to > 2 mg/dL (43% vs. 22%, respectively; P = 0.021) were more common with L-AmB. Infusion-related reactions were noted in five L-AmB-treated patients. Responses to chemotherapy and induction mortality rates were similar for the two arms. CONCLUSIONS. L-AmB and F+I appear similar in their efficacy as antifungal prophylaxis during induction chemotherapy for patients with AML and MDS. L-AmB was associated with higher rates of increased serum bilirubin and creatinine levels.

Original languageEnglish (US)
Pages (from-to)450-456
Number of pages7
JournalCancer
Volume97
Issue number2
DOIs
StatePublished - Jan 15 2003
Externally publishedYes

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Induction Chemotherapy
Itraconazole
Fluconazole
Myelodysplastic Syndromes
Acute Myeloid Leukemia
Mycoses
Bilirubin
liposomal amphotericin B
Invasive Fungal Infections
Creatinine
Serum
Mortality
Complementary Therapies
Tablets
Pneumonia
Fever

Keywords

  • Acute leukemia
  • Fungal infection
  • Myelodysplastic syndrome
  • Prophylaxis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during induction : Chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome. / Mattiuzzi, Gloria N.; Estey, Elihu; Raad, Issam; Giles, Francis; Cortes, Jorge; Shen, Yu; Kontoyiannis, Dimitrios; Koller, Charles; Munsell, Mark; Beran, Miloslav; Kantarjian, Hagop.

In: Cancer, Vol. 97, No. 2, 15.01.2003, p. 450-456.

Research output: Contribution to journalArticle

Mattiuzzi, Gloria N. ; Estey, Elihu ; Raad, Issam ; Giles, Francis ; Cortes, Jorge ; Shen, Yu ; Kontoyiannis, Dimitrios ; Koller, Charles ; Munsell, Mark ; Beran, Miloslav ; Kantarjian, Hagop. / Liposomal amphotericin B versus the combination of fluconazole and itraconazole as prophylaxis for invasive fungal infections during induction : Chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome. In: Cancer. 2003 ; Vol. 97, No. 2. pp. 450-456.
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abstract = "BACKGROUND. Fungal infections are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The authors evaluated the efficacy and toxicity of liposomal amphotericin B (L-AmB) compared with a combination of fluconazole plus itraconazole (F+I) as prophylaxis in this setting. METHODS. Patients with newly diagnosed AML or high-risk MDS who were undergoing initial induction chemotherapy were randomized to receive either F+I (fluconazole 200 mg orally every 12 hours plus itraconazole tablets 200 mg orally every 12 hours) or L-AmB (3 mg/kg intravenously 3 times per week) in this prospective, open-label study. RESULTS. Seventy-two L-AmB-treated patients and 67 F+I-treated patients were enrolled in the study. Of these, 47{\%} of patients completed antifungal prophylaxis without a change in therapy for proven or suspected fungal infection. Three patients in each arm developed a proven fungal infection. Twenty-three percent of the L-AmB-treated patients and 24{\%} of the F+I-treated patients were changed to alternative antifungal therapy because of persistent fever (P value not significant). Nine percent of the L-AmB-treated patients developed pneumonia of unknown etiology compared with 16{\%} of the F+I-treated patients (P value not significant). Increases in serum creatinine levels to > 2 mg/dL (20{\%} for the L-AmB arm vs. 6{\%} for the F+I arm; P = 0.012) and increases in serum bilirubin levels to > 2 mg/dL (43{\%} vs. 22{\%}, respectively; P = 0.021) were more common with L-AmB. Infusion-related reactions were noted in five L-AmB-treated patients. Responses to chemotherapy and induction mortality rates were similar for the two arms. CONCLUSIONS. L-AmB and F+I appear similar in their efficacy as antifungal prophylaxis during induction chemotherapy for patients with AML and MDS. L-AmB was associated with higher rates of increased serum bilirubin and creatinine levels.",
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author = "Mattiuzzi, {Gloria N.} and Elihu Estey and Issam Raad and Francis Giles and Jorge Cortes and Yu Shen and Dimitrios Kontoyiannis and Charles Koller and Mark Munsell and Miloslav Beran and Hagop Kantarjian",
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T2 - Chemotherapy for patients with acute myelogenous leukemia and myelodysplastic syndrome

AU - Mattiuzzi, Gloria N.

AU - Estey, Elihu

AU - Raad, Issam

AU - Giles, Francis

AU - Cortes, Jorge

AU - Shen, Yu

AU - Kontoyiannis, Dimitrios

AU - Koller, Charles

AU - Munsell, Mark

AU - Beran, Miloslav

AU - Kantarjian, Hagop

PY - 2003/1/15

Y1 - 2003/1/15

N2 - BACKGROUND. Fungal infections are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The authors evaluated the efficacy and toxicity of liposomal amphotericin B (L-AmB) compared with a combination of fluconazole plus itraconazole (F+I) as prophylaxis in this setting. METHODS. Patients with newly diagnosed AML or high-risk MDS who were undergoing initial induction chemotherapy were randomized to receive either F+I (fluconazole 200 mg orally every 12 hours plus itraconazole tablets 200 mg orally every 12 hours) or L-AmB (3 mg/kg intravenously 3 times per week) in this prospective, open-label study. RESULTS. Seventy-two L-AmB-treated patients and 67 F+I-treated patients were enrolled in the study. Of these, 47% of patients completed antifungal prophylaxis without a change in therapy for proven or suspected fungal infection. Three patients in each arm developed a proven fungal infection. Twenty-three percent of the L-AmB-treated patients and 24% of the F+I-treated patients were changed to alternative antifungal therapy because of persistent fever (P value not significant). Nine percent of the L-AmB-treated patients developed pneumonia of unknown etiology compared with 16% of the F+I-treated patients (P value not significant). Increases in serum creatinine levels to > 2 mg/dL (20% for the L-AmB arm vs. 6% for the F+I arm; P = 0.012) and increases in serum bilirubin levels to > 2 mg/dL (43% vs. 22%, respectively; P = 0.021) were more common with L-AmB. Infusion-related reactions were noted in five L-AmB-treated patients. Responses to chemotherapy and induction mortality rates were similar for the two arms. CONCLUSIONS. L-AmB and F+I appear similar in their efficacy as antifungal prophylaxis during induction chemotherapy for patients with AML and MDS. L-AmB was associated with higher rates of increased serum bilirubin and creatinine levels.

AB - BACKGROUND. Fungal infections are a major cause of morbidity and mortality in patients undergoing induction chemotherapy for acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). The authors evaluated the efficacy and toxicity of liposomal amphotericin B (L-AmB) compared with a combination of fluconazole plus itraconazole (F+I) as prophylaxis in this setting. METHODS. Patients with newly diagnosed AML or high-risk MDS who were undergoing initial induction chemotherapy were randomized to receive either F+I (fluconazole 200 mg orally every 12 hours plus itraconazole tablets 200 mg orally every 12 hours) or L-AmB (3 mg/kg intravenously 3 times per week) in this prospective, open-label study. RESULTS. Seventy-two L-AmB-treated patients and 67 F+I-treated patients were enrolled in the study. Of these, 47% of patients completed antifungal prophylaxis without a change in therapy for proven or suspected fungal infection. Three patients in each arm developed a proven fungal infection. Twenty-three percent of the L-AmB-treated patients and 24% of the F+I-treated patients were changed to alternative antifungal therapy because of persistent fever (P value not significant). Nine percent of the L-AmB-treated patients developed pneumonia of unknown etiology compared with 16% of the F+I-treated patients (P value not significant). Increases in serum creatinine levels to > 2 mg/dL (20% for the L-AmB arm vs. 6% for the F+I arm; P = 0.012) and increases in serum bilirubin levels to > 2 mg/dL (43% vs. 22%, respectively; P = 0.021) were more common with L-AmB. Infusion-related reactions were noted in five L-AmB-treated patients. Responses to chemotherapy and induction mortality rates were similar for the two arms. CONCLUSIONS. L-AmB and F+I appear similar in their efficacy as antifungal prophylaxis during induction chemotherapy for patients with AML and MDS. L-AmB was associated with higher rates of increased serum bilirubin and creatinine levels.

KW - Acute leukemia

KW - Fungal infection

KW - Myelodysplastic syndrome

KW - Prophylaxis

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