New Drugs and Novel Targets for Treatment of Invasive Fungal Infections in Patients with Cancer

Chiou, Christine C.; Groll, Andreas H.; Walsh, Thomas J.

doi:10.1634/theoncologist.5-2-120

Cited by 106 publications

(54 citation statements)

References 116 publications

(107 reference statements)

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“…Up to now, amphotericin B is the standard treatment for IFI. 1,3,4 Amphotericin B is a broad-spectrum, effective antifungal agent, but its use is associated with nephrotoxicity and infusion-related side effects. 5,6 To date, no efficient salvage therapy has been available if amphotericin B fails to clear the infection, or if the patient is intolerant to amphotericin B.…”

Section: Invasive Fungal Infectionmentioning

confidence: 99%

“…They act by inhibiting the synthesis of 1,3-b-D glucan, which is an important component of the fungal cell wall. 4,[7][8][9] Caspofungin (CAS) is the first antifungal agent in this new class. CAS has proven to be effective and well tolerated in the treatment of infections caused by Aspergillus spp, Candida albicans and non-C. albicans spp.…”

Section: Invasive Fungal Infectionmentioning

confidence: 99%

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Caspofungin as second-line therapy for fever of unknown origin or invasive fungal infection following allogeneic stem cell transplantation

Trenschel

Ditschkowski

Elmaagacli

et al. 2005

Bone Marrow Transplant

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Section: Invasive Fungal Infectionmentioning

confidence: 99%

Section: Invasive Fungal Infectionmentioning

confidence: 99%

Caspofungin as second-line therapy for fever of unknown origin or invasive fungal infection following allogeneic stem cell transplantation

Trenschel

Ditschkowski

Elmaagacli

et al. 2005

Bone Marrow Transplant

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“…Caspofungin belongs to the echinocandin class of antimycotics which inhibit b-1,3-D-glucan synthesis in the fungal cell wall. Both voriconazole and caspofungin are effective in the therapy of Aspergillus and Candida (including non-albicans Candida species) infections [27][28][29][30].…”

Section: Antifungal Agents Used In the Treatment Of Invasive Fungal Imentioning

confidence: 99%

Modern management of respiratory failure due to pulmonary mycoses following allogeneic hematopoietic stem‐cell transplantation

Koldehoff

Zakrzewski

2005

American J Hematol

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Pulmonary mycoses count among the most dangerous complications in allogeneic hematopoietic stem cell transplantation. Despite the establishment of antifungal chemoprophylaxis and empirical antifungal treatment, they frequently lead to respiratory failure and are still associated with an extraordinarily poor prognosis. However, the emergence of new antimycotics with alternative mechanisms of actions and decreased toxicity in combination with the development of new non culture-based diagnostic techniques may allow earlier, more aggressive and more effective antifungal treatment approaches. In addition, the optimized use of new technologies designed to augment spontaneous breathing efforts by patients, mechanical ventilation, as well as the advantages of early tracheostomy lead us to expect better outcomes in the treatment of respiratory failure due to pulmonary mycoses following allogeneic hematopoietic stem cell transplantation.

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“…Developed as intravenous and oral formulations, voriconazole is a novel antifungal triazole with potent in vitro and in vivo activity against a broad spectrum of medically important pathogens, including Aspergillus, Cryptococcus, and Candida species (4,6,12). Recent studies have characterized the in vivo pharmacokinetics and pharmacodynamics of voriconazole in a murine model of disseminated candidiasis (1).…”

mentioning

confidence: 99%

Pharmacokinetics and Safety of Intravenous Voriconazole in Children after Single- or Multiple-Dose Administration

Walsh

Karlsson

Driscoll

et al. 2004

Antimicrob Agents Chemother

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308

234

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We conducted a multicenter study of the safety, tolerability, and plasma pharmacokinetics of the parenteral formulation of voriconazole in immunocompromised pediatric patients (2 to 11 years old). Single doses of 3 or 4 mg/kg of body weight were administered to six and five children, respectively. In the multiple-dose study, 28 patients received loading doses of 6 mg/kg every 12 h on day 1, followed by 3 mg/kg every 12 h on day 2 to day 4 and 4 mg/kg every 12 h on day 4 to day 8. Standard population pharmacokinetic approaches and generalized additive modeling were used to construct the structural pharmacokinetic and covariate models used in this analysis. In contrast to that in adult healthy volunteers, elimination of voriconazole was linear in children following doses of 3 and 4 mg/kg every 12 h. Body weight was more influential than age in accounting for the observed variability in voriconazole pharmacokinetics. Elimination capacity correlated with the CYP2C19 genotype. Exposures were similar at 4 mg/kg every 12 h in children (median area under the concentration-time curve (AUC), 14,227 ng ⅐ h/ml) and 3 mg/kg in adults (median AUC, 13,855 ng ⅐ h/ml). Visual disturbances occurred in 5 (12.8%) of the 39 patients and were the only drug-related adverse events that occurred more than once. No withdrawals from the study were related to voriconazole. We conclude that pediatric patients have a higher capacity for elimination of voriconazole per kilogram of body weight than do adult healthy volunteers and that dosages of 4 mg/kg may be required in children to achieve exposures consistent with those in adults following dosages of 3 mg/kg.

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New Drugs and Novel Targets for Treatment of Invasive Fungal Infections in Patients with Cancer

Cited by 106 publications

References 116 publications

Caspofungin as second-line therapy for fever of unknown origin or invasive fungal infection following allogeneic stem cell transplantation

Caspofungin as second-line therapy for fever of unknown origin or invasive fungal infection following allogeneic stem cell transplantation

Modern management of respiratory failure due to pulmonary mycoses following allogeneic hematopoietic stem‐cell transplantation

Pharmacokinetics and Safety of Intravenous Voriconazole in Children after Single- or Multiple-Dose Administration

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