Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies

Kontoyiannis, Dimitrios P.; Hachem, Ray; Lewis, Russell E.; Rivero, Gustavo; Torres, Harrys A.; Thornby, John; Champlin, Richard E.; Kantarjian, Hagop; Bodey, Gerald P.; Raad, Issam

doi:10.1002/cncr.11479

Cited by 273 publications

(206 citation statements)

References 37 publications

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“…Studies such as this may help reassure us that we are not doing any harm to patients but on the other hand, it is impossible to appreciate in these salvage studies which single or combination regimens are most successful. 37,38 The next step has been to study prospectively combination antifungal therapy for primary disease and this has been reported for an azole plus echinocandin, but there have been no blinded or randomized comparative trials and thus accurate insights into success of combination therapies are still uncertain. 39 In this study, the combination of voriconazole plus caspofungin as primary therapy for invasive aspergillosis in solid organ transplant recipients was compared to historical controls managed with a lipid formulation of amphotericin B. Ninety-day survival was 67.5% (27/40) among those who received combination antifungal therapy compared to 51% (24/47) of controls (HR 0.57, 95% CI 0.29-1.1).…”

Section: Challenge Recommendationmentioning

confidence: 99%

Combination antifungal therapy: what can and should we expect?

Johnson

Perfect

2007

Bone Marrow Transplant

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Section: Challenge Recommendationmentioning

confidence: 99%

Combination antifungal therapy: what can and should we expect?

Johnson

Perfect

2007

Bone Marrow Transplant

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“…50 Response rates from retrospective reports in heterogeneous patient populations have been inconsistent. 45,53,54 Favorable responses were observed among HSCT patients failing polyene-based therapy for invasive aspergillosis with a combination of voriconazole and caspofungin compared to voriconazole monotherapy. 55 Only one recent randomized-controlled trial in IC suggested that a combination of fluconazole and amphotericin B deoxycholate may have advantages over fluconazole monotherapy.…”

Section: Salvage Monotherapymentioning

confidence: 99%

Of Yeasts and Hyphae: A Hematologist’s Approach to Antifungal Therapy

Bow¹

2006

Hematology

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Improvements in anticancer treatments, the ability to modify myelosuppression profiles, greater duration and intensity of immunosuppression, and the variety of available antimicrobial therapies have influenced the spectrum of pathogens associated with invasive fungal infection complicating treatment of hematological malignancies and hematopoietic stem cell transplantation. The approaches to the management of these infections encompass strategies of prevention for all those at risk, pre-emptive therapy based upon surrogates of infection before the onset of clinical disease, empirical therapy for patients with clinical evidence of early disease, and directed or targeted therapy for infected patients with established disease. Chemoprophylaxis is effective if applied to the highest risk patients over the duration of the risk. Pre-emptive strategies, while promising, have yet to be validated and linked to reliably predictive nonmicrobiological diagnostic techniques. Empirical antifungal therapy, as it is currently applied, now seems questionable. Patients with probable or proven invasive fungal infection still have suboptimal outcomes despite the availability of promising anti-fungal agents. Strategies examining the concept of dose-intensity and combination regimens require careful study and cannot yet be regarded as an acceptable standard of practice. Changing Epidemiology of Invasive Fungal Infection in Hematological Malignancies and Stem Cell TransplantsInterest in the field of medical mycology has expanded considerably as the numbers of immuno-and myelo-suppressed patients susceptible to opportunistic invasive fungal infections (IFI) increase. While the majority (95-97%) of invasive yeast infections are due to five species, predominantly Candida albicans, followed by C. tropicalis, C. glabrata, C. parapsilosis, and C. krusei, emerging importance of infections due to non-albicans Candida spp. including C. glabrata, C. parapsilosis, and C. krusei in high-risk cancer patients is noteworthy. 1 The remaining 3% to 5% of pathogens include other non-albicans Candida spp.. and non-Candida yeasts such as Trichosporon spp., Cryptococcus spp., Blastoschizomyces spp., and Malassezia spp.. 2,3 The risks for IFI among hematopoietic stem cell transplants (HSCT) increases as the disparity of the donor:recipient pair (autologous HSCT, 0.6%; matched related donor HSCT, 3.7%; mismatched related or unrelated donor HSCT, 5.9%, P < 0.0001). 4 The changing character of the HSCT populations together with effective antiCandida agents contribute to a changing spectrum of opportunistic mycoses. In a comparison of transplant patients with IFI to a more general population of patients at risk, the proportion of Candida infections decreased by approximately 45% (77% to 42%); however, that due to Aspergillus spp. has more than doubled (13% to 29%) and that due to other environmental moulds including Fusarium spp., Scedosporium spp., the zygomycetes, and the less com-

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“…Los resultados de la aplicación de las combinaciones de voriconazol o anfotericina B liposomal con caspofungina [23][24][25] (BII) no son excesivamente alentadores, ya que el éxito terapéutico es parecido al hallado en controles históricos de pacientes con aspergilosis pulmonar invasiva tratados con cada fármaco por separado. En cualquier caso, el número global de pacientes es muy pequeño y sería recomendable la realización de un ensayo clínico controlado con un número más elevado.…”

Section: Tratamiento Antifúngicounclassified

Recomendaciones para el tratamiento de la infección por Aspergillus spp.

Gavaldá¹,

Ruíz²

2003

Enferm Infecc Microbiol Clin

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más de un órgano. Las manifestaciones clínicas son diferentes según la enfermedad de base del paciente.Aspergillus spp. puede causar cinco tipos diferentes de enfermedad: la aspergilosis cutánea primaria, que es una forma de enfermedad localizada pero con la posibilidad de diseminación. La aspergilosis pulmonar, que es la forma de presentación más frecuente en los pacientes neutropénicos (80-90%), sobre todo en la forma aguda invasiva. La variante crónica necrosante es menos frecuente y se observa en pacientes con infección por virus de la inmunodeficiencia humana (VIH), enfermedad granulomatosa crónica, alcoholismo y tratamiento prolongado con corticoides (neumopatías crónicas). La enfermedad de vía aérea, que puede presentarse como traqueobronquitis con o sin invasión en forma de úlceras o nódulos, se denomina traqueobronquitis invasiva o aspergilosis bronquial invasiva, y es casi exclusiva del paciente trasplantado de pulmón. La sinusitis por Aspergillus es también más frecuente en el paciente neutropénico (5-10%). Finalmente, desde los pulmones, Aspergillus spp., mediante angioinvasión puede diseminar a casi cualquier órgano del cuerpo, especialmente el cerebro, hígado, bazo y el tracto gastrointestinal produciendo una enfermedad diseminada. La infección invasiva por Aspergillus spp. presenta una elevada mortalidad dependiendo de su localización que puede oscilar entre el 37% en las formas traqueobronquiales hasta ser superior al 80% en las formas diseminadas con afectación del sistema nervioso central (SNC) a pesar de la utilización de anfotericina B 2 .A. fumigatus es la especie que con más frecuencia causa enfermedad invasiva en enfermos inmunodeprimidos. Otras especies implicadas son: A. flavus, A. niger, A. terreus, A. nidulans, A. versicolor, A. glaucus, etc. A. niger se aísla más a menudo en casos de otomicosis y como colonizante.Para intentar disminuir la elevada mortalidad relacionada con la infección fúngica invasiva, es imprescindible realizar un diagnóstico lo más precoz posible y administrar un tratamiento antifúngico agresivo 3 . Aunque no siempre es posible, debe intentarse disminuir o retirar la inmunosupresión o bien, aumentar la capacidad inmunológica de defensa del huésped y la cifra de neutrófilos.El diagnóstico precoz y el inicio inmediato del tratamiento, deberían reducir la mortalidad relacionada con esta infección. El problema reside en que en la actualidad no están a nuestra disposición técnicas que permitan esta aproximación terapéutica-diagnóstica. La utilización de técnicas como la reacción en cadena de la polimerasa (PCR) (específica para Aspergillus spp. o general para la detección de cualquier hongo o levadura-panfungal) o la detección de antígeno de Aspergillus spp., han demostrado su eficacia en el paciente con leucemia o trasplantado de órgano sólido, Guidelines for the treatment of infection due to Aspergillus spp. IntroducciónEn esta reunión de consenso se abordó únicamente la aspergilosis invasiva, no se establecieron recomendaciones para el tratamiento del aspergiloma...

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Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies

Cited by 273 publications

References 37 publications

Combination antifungal therapy: what can and should we expect?

Combination antifungal therapy: what can and should we expect?

Of Yeasts and Hyphae: A Hematologist’s Approach to Antifungal Therapy

Recomendaciones para el tratamiento de la infección por Aspergillus spp.

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