Safety and Efficacy of Posaconazole for the Treatment of Invasive Fungal Infections After Failure of One Prior Line of Therapy
Notice bibliographique
Résumé
Abstract Abstract 4479 Background: Invasive fungal infection (IFI) is a common problem during AML induction or Graft Versus Host Disease (GVHD). Several options are available as first line therapies. However, second line interventions are limited by cumulative toxicities, drug interactions, and potential resistance are often encountered. Posaconazole is a triazole antifungal with broad yeast and mould coverage and possesses a favorable toxicity profile. Prior studies using posaconazole for refractory IFI involved patients with multiple antifungal exposure, thus the efficacy in second line therapy is unclear. Methods: A single arm phase II multicenter study of posaconazole in patients with IFIs who failed or were intolerant to other antifungal therapy. The primary objectives of the study were the safety and efficacy of posaconazole; safety was evaluated in all patients who received at least one dose of study drug; efficacy was assessed in patients who remained on therapy for at least one evaluation after baseline. (Evaluations were performed after 3, 6, 12, 26, 39 and 52 weeks of therapy) Results: Thirty seven patients with proven (35%), probable (34%) and possible (31%) IFIs were included in the study. Conditions leading to IFI were hematological malignancies (36%), stem cell transplant (27%) solid organ transplant (22%), pulmonary disease (11%) and others (5%). The study population included mainly patients refractory (70%) and/or intolerant (25%) to prior anti-fungal. First line therapy included voriconazole (49%), amphotericin B (24%), fluconazole (14%) and others (11%). Identified pathogens were Aspergillus (50%), Candida (20%) and Zygomycetes (10%) and others (20%). Efficacy could be evaluated in 27 patients. Overall response in proven or probable IFI was 56% including 10% CR and 45% PR. Safety was assessed in all 37 patients and a special attention was given to liver toxicity since it is a common problem in hematological malignancies and transplant patients. More than 40% of patients entered the study with elevated liver enzymes most of whom (70%) received prior azole therapy. Of those, 75% had normalization of their liver enzymes within 12 weeks of posaconazole initiation. Normalization usually occurred during the first month, but some patients experienced transient liver enzyme elevation during the first few weeks of therapy. Common toxicities reported irrespective of causality were: nausea & vomiting (26%), diarrhea (26%), rash (15%), edema (12%) and elevated liver enzymes (9%). No grade 4 toxicities were reported. Conclusion: Posaconazole was an effective therapy in patients with refractory IFI previously treated with other antifungal therapy. Switching from another azole to posaconazole was also possible even in patients with hepatic dysfunction at study start. Disclosures: Galarneau: Merck: Employment. Pouliot:Merck Canada: Employment.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».