Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis

Johan Maertens, Axel Glasmacher, Raoul Herbrecht, Anne Thiebaut, Catherine Cordonnier, Brahm H. Segal, John Killar, Arlene Taylor, Nicholas Kartsonis, Thomas F Patterson

Research output: Contribution to journalArticle

178 Citations (Scopus)

Abstract

BACKGROUND. Caspofungin inhibits synthesis of β-1,3-glucan, an essential component of the Aspergillus cell wall. This echinocandin has demonstrated efficacy (45% success) as salvage monotherapy of invasive aspergillosis (IA). Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA. METHODS. The study involved 53 adults with documented IA who were refractory to or intolerant of standard antifungal therapy and received caspofungin and 1 other mold-active antifungal agent (at the investigator's discretion). Efficacy was assessed by signs, symptoms, and radiographs at the end of combination therapy and Day 84 after combination therapy initiation. Favorable (complete or partial) responses required significant clinical and radiographic improvement. Diagnoses and outcomes were assessed by an independent expert. RESULTS. Among the 53 patients enrolled the most common underlying diseases were acute leukemia (53%), lymphoma (11%), and chronic leukemia (6%). Pulmonary aspergillosis (81%) was the most common site, and most patients (87%) were refractory to prior therapy. Success at the end of combination therapy and Day 84 was 55% (29/53) and 49% (25/51), respectively. Fifty-seven percent of patients with neutropenia and 54% who received an allogeneic hematopoietic stem cell transplant responded favorably. Survival at Day 84 was 55%. Combination therapy, dosed on average for 31.3 days, was well tolerated. Two (4%) serious drug-related adverse events, both attributed to voriconazole, occurred. None of the patients discontinued caspofungin due to toxicity. CONCLUSION. Caspofungin in combination with a triazole or polyene was an effective alternative as salvage therapy for patients with recalcitrant Aspergillus infections.

Original languageEnglish (US)
Pages (from-to)2888-2897
Number of pages10
JournalCancer
Volume107
Issue number12
DOIs
StatePublished - Dec 15 2006

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caspofungin
Salvage Therapy
Aspergillosis
Multicenter Studies
Aspergillus
Leukemia
Therapeutics
Echinocandins
Pulmonary Aspergillosis
Polyenes
Triazoles
Glucans
Antifungal Agents
Acute Disease
Hematopoietic Stem Cells
Neutropenia
Drug-Related Side Effects and Adverse Reactions
Cell Wall
Signs and Symptoms
Lymphoma

Keywords

  • Aspergillosis
  • Caspofungin
  • Combination therapy
  • Salvage therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis. / Maertens, Johan; Glasmacher, Axel; Herbrecht, Raoul; Thiebaut, Anne; Cordonnier, Catherine; Segal, Brahm H.; Killar, John; Taylor, Arlene; Kartsonis, Nicholas; Patterson, Thomas F.

In: Cancer, Vol. 107, No. 12, 15.12.2006, p. 2888-2897.

Research output: Contribution to journalArticle

Maertens, J, Glasmacher, A, Herbrecht, R, Thiebaut, A, Cordonnier, C, Segal, BH, Killar, J, Taylor, A, Kartsonis, N & Patterson, TF 2006, 'Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis', Cancer, vol. 107, no. 12, pp. 2888-2897. https://doi.org/10.1002/cncr.22348
Maertens, Johan ; Glasmacher, Axel ; Herbrecht, Raoul ; Thiebaut, Anne ; Cordonnier, Catherine ; Segal, Brahm H. ; Killar, John ; Taylor, Arlene ; Kartsonis, Nicholas ; Patterson, Thomas F. / Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis. In: Cancer. 2006 ; Vol. 107, No. 12. pp. 2888-2897.
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abstract = "BACKGROUND. Caspofungin inhibits synthesis of β-1,3-glucan, an essential component of the Aspergillus cell wall. This echinocandin has demonstrated efficacy (45{\%} success) as salvage monotherapy of invasive aspergillosis (IA). Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA. METHODS. The study involved 53 adults with documented IA who were refractory to or intolerant of standard antifungal therapy and received caspofungin and 1 other mold-active antifungal agent (at the investigator's discretion). Efficacy was assessed by signs, symptoms, and radiographs at the end of combination therapy and Day 84 after combination therapy initiation. Favorable (complete or partial) responses required significant clinical and radiographic improvement. Diagnoses and outcomes were assessed by an independent expert. RESULTS. Among the 53 patients enrolled the most common underlying diseases were acute leukemia (53{\%}), lymphoma (11{\%}), and chronic leukemia (6{\%}). Pulmonary aspergillosis (81{\%}) was the most common site, and most patients (87{\%}) were refractory to prior therapy. Success at the end of combination therapy and Day 84 was 55{\%} (29/53) and 49{\%} (25/51), respectively. Fifty-seven percent of patients with neutropenia and 54{\%} who received an allogeneic hematopoietic stem cell transplant responded favorably. Survival at Day 84 was 55{\%}. Combination therapy, dosed on average for 31.3 days, was well tolerated. Two (4{\%}) serious drug-related adverse events, both attributed to voriconazole, occurred. None of the patients discontinued caspofungin due to toxicity. CONCLUSION. Caspofungin in combination with a triazole or polyene was an effective alternative as salvage therapy for patients with recalcitrant Aspergillus infections.",
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T1 - Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis

AU - Maertens, Johan

AU - Glasmacher, Axel

AU - Herbrecht, Raoul

AU - Thiebaut, Anne

AU - Cordonnier, Catherine

AU - Segal, Brahm H.

AU - Killar, John

AU - Taylor, Arlene

AU - Kartsonis, Nicholas

AU - Patterson, Thomas F

PY - 2006/12/15

Y1 - 2006/12/15

N2 - BACKGROUND. Caspofungin inhibits synthesis of β-1,3-glucan, an essential component of the Aspergillus cell wall. This echinocandin has demonstrated efficacy (45% success) as salvage monotherapy of invasive aspergillosis (IA). Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA. METHODS. The study involved 53 adults with documented IA who were refractory to or intolerant of standard antifungal therapy and received caspofungin and 1 other mold-active antifungal agent (at the investigator's discretion). Efficacy was assessed by signs, symptoms, and radiographs at the end of combination therapy and Day 84 after combination therapy initiation. Favorable (complete or partial) responses required significant clinical and radiographic improvement. Diagnoses and outcomes were assessed by an independent expert. RESULTS. Among the 53 patients enrolled the most common underlying diseases were acute leukemia (53%), lymphoma (11%), and chronic leukemia (6%). Pulmonary aspergillosis (81%) was the most common site, and most patients (87%) were refractory to prior therapy. Success at the end of combination therapy and Day 84 was 55% (29/53) and 49% (25/51), respectively. Fifty-seven percent of patients with neutropenia and 54% who received an allogeneic hematopoietic stem cell transplant responded favorably. Survival at Day 84 was 55%. Combination therapy, dosed on average for 31.3 days, was well tolerated. Two (4%) serious drug-related adverse events, both attributed to voriconazole, occurred. None of the patients discontinued caspofungin due to toxicity. CONCLUSION. Caspofungin in combination with a triazole or polyene was an effective alternative as salvage therapy for patients with recalcitrant Aspergillus infections.

AB - BACKGROUND. Caspofungin inhibits synthesis of β-1,3-glucan, an essential component of the Aspergillus cell wall. This echinocandin has demonstrated efficacy (45% success) as salvage monotherapy of invasive aspergillosis (IA). Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA. METHODS. The study involved 53 adults with documented IA who were refractory to or intolerant of standard antifungal therapy and received caspofungin and 1 other mold-active antifungal agent (at the investigator's discretion). Efficacy was assessed by signs, symptoms, and radiographs at the end of combination therapy and Day 84 after combination therapy initiation. Favorable (complete or partial) responses required significant clinical and radiographic improvement. Diagnoses and outcomes were assessed by an independent expert. RESULTS. Among the 53 patients enrolled the most common underlying diseases were acute leukemia (53%), lymphoma (11%), and chronic leukemia (6%). Pulmonary aspergillosis (81%) was the most common site, and most patients (87%) were refractory to prior therapy. Success at the end of combination therapy and Day 84 was 55% (29/53) and 49% (25/51), respectively. Fifty-seven percent of patients with neutropenia and 54% who received an allogeneic hematopoietic stem cell transplant responded favorably. Survival at Day 84 was 55%. Combination therapy, dosed on average for 31.3 days, was well tolerated. Two (4%) serious drug-related adverse events, both attributed to voriconazole, occurred. None of the patients discontinued caspofungin due to toxicity. CONCLUSION. Caspofungin in combination with a triazole or polyene was an effective alternative as salvage therapy for patients with recalcitrant Aspergillus infections.

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KW - Combination therapy

KW - Salvage therapy

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